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Full immunization coverage and its associated factors among children aged 12–23 months in Ethiopia: further analysis from the 2016 Ethiopia demographic and health survey
- Koku Sisay Tamirat 1 &
- Malede Mequanent Sisay 1
BMC Public Health volume 19 , Article number: 1019 ( 2019 ) Cite this article
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Vaccination is one of the cost effective strategies reducing childhood morbidity and mortality. Further improvement of immunization coverage would halt about 1.5 million additional deaths globally. Understanding the level of immunization among children is vital to design appropriate interventions. Therefore, this study aimed to assess full immunization coverage and its determinants among children aged 12–23 months in Ethiopia.
The study was based on secondary data analysis from the 2016 Ethiopia Demographic and Health Survey (EDHS). Information about 1,909 babies aged 12–23 months was extracted from children dataset. Both bivariate and multivariable logistic regression models were utilized to assess the status and factors associated with full immunization. Adjusted odds ratio (AOR) with a 95% confidence interval (CI) was computed. Variables with less than 0.05 p -values in the multivariable logistic regression model were considered as statistically and significantly associated with the outcome variable.
The overall full immunization coverage was 38.3% (95% CI: 36.7, 41.2). Rural residence (AOR = 0.60, 95% CI: 0.43, 0.84), employed (AOR = 1.62, 95% CI: 1.31, 2.0), female household head (AOR = 0.58, 95% CI: 0.44, 0.76), wealth index [middle (AOR = 1.44, 95% CI: 1.07, 1.94) and richness (AOR = 1.65, 95% CI: 1.25,2.19)], primary school maternal education (AOR = 1.38,95% CI: 1.07, 1.78), secondary school maternal education (AOR = 2.19, 95% CI: 1.43, 3.36), diploma graduated mothers (AOR = 1.99, 95% CI: 1.09, 3.61), ANC follow ups (AOR = 2.79, 95% CI:2.17 3.59), and delivery at health facilities (AOR = 1.76, 95% CI: 1.36, 2.24) were significantly associated factors with full immunization.
Full immunization coverage in Ethiopia was significantly lower than the global target. Female household head and rural dwellings were negatively associated with full immunization. In contrast higher maternal education, employment, middle and rich economic status, ANC follow up, and delivery at health facility were positively associated with full immunization among 12–23 months old children. This suggests that improved health education and service expansion to remote areas are necessary to step immunization access.
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Vaccination is one of the prevention strategies for common childhood illnesses. It prevents morbidities and mortalities from diphtheria, hepatitis B, measles, mumps, pertussis, pneumonia, polio, rotavirus diarrhea, rubella, cervical cancer, and tetanus [ 1 , 2 ]. Vaccine preventable diseases (VPDs) account for 17% of the global under five mortality per annum [ 3 ]. According to World Health Organization (WHO) 2017 report, 116.2 million infants (85%) received the third doses of DPT, and worldwide, 123 countries reached the third dose of diphtheria, pertussis, and tetanus (DPT3) coverage to 90%. Despite the increasing uptake of new and underused vaccines, still an estimated 19.9 million children under the age of 1 year have not received DTP3 vaccine [ 1 , 4 , 5 , 6 ]. Further improvement of global immunization coverage would prevent an additional 1.5 million deaths [ 3 ]. According to a case-based surveillance, the annual incidence of measles was estimated at 29.1 cases per 1 million people [ 7 ].
Expanded program of immunization (EPI) was launched by WHO in 1974 with the objectives of reducing morbidity and mortality from six VPDs. Ethiopia started the EPI program in 1980 with a longer-term goal of achieving 90% DPT3 coverage in all regions through strategies of reaching every district (RED) and sustainable outreach service (SOS) approaches. In the Ethiopia health care system, immunization is provided free of charge and services are available from the smallest health post level to the highest hospitals [ 8 ].
According to guidelines developed by the World Health Organization (WHO), children are considered fully immunized when they have received one dose of Bacillus Calmette Guerin (BCG), three doses of DPT, three doses of polio vaccines, and one dose of measles vaccination by the age of 9–12 months [ 9 , 10 ]. Ethiopia has incorporated Haemophilus influenza type B (HiB) and hepatitis-B (HepB) antigens to the previous DPT vaccines and replaced as Pentavalent vaccine (DPT plus Hep B and Hib) [ 1 , 3 , 8 , 11 ]. A variety of vaccines, of which the Pneumococcal conjugate vaccine (PCV), Rota, and Human papilloma (HPV) vaccines were the most recent have been introduced into the national EPI service overtime. Different findings showed that the proportion of full immunization coverage in the country ranged from 36.6% in Somalia region to 100% in Addis Ababa [ 1 , 4 , 10 , 12 , 13 , 14 , 15 , 16 , 17 ]. Factors associated with child full immunization included socio-demographic characteristics (maternal educational status and residence), health service delivery (place of delivery, ANC follow up, vaccine availability residence, and cold chain management) [ 1 , 4 , 10 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 ].
Although some community based works are available with different findings, no study has shown the overall national full immunization coverage after the new vaccines have been introduced into the EPI schedule. Therefore, the objective of this study was to measure the full immunization coverage and associated factors among children aged 12–23 months in Ethiopia in order to help planners assess the progress of the national full immunization coverage.
Data source
The data used in this paper is from the 2016 Ethiopian Demographic and Health Survey report. Ethiopia is the second largest populous country in Africa with 102.4 million people and an annual population growth rate of 2.5%. The country is divided into nine regional and two-city administrations and has a three-tier health care system with the primary care facilities situated in nearby communities.
The two stage stratified sampling technique/ method was used for the survey. Initially, the enumeration area were stratified into urban and rural. The first stage involved selecting clusters, within the enumeration areas. The second stage was a systematic listing of households in the selected clusters. Out of each cluster 28 households were randomly selected to constitute the total sample size of households. Out of 7,193 women who gave birth in the past 5 years preceding of the survey, 5,980 were interviewed about the vaccination status of their children, and data gathered from 1,909 of the mothers who had children aged 12–23 months of were analyzed [ 23 ].
Measurement of variables
Full immunization was the response variable, whereas socio-demographic characteristics (age, residence, religion, marital status), reproductive health history (place of delivery, birth order, antenatal care and postnatal care follow up) were the independent variables.
The information in the 2016 EDHS report on vaccination coverage was collected from immunization cards shown to the interviewers and from mothers’ verbal responses. When cards were available, the interviewer copied the vaccination dates directly onto questionnaires. When vaccination cards were not available for the child or if the vaccine was not recorded on the card as being given, the respondents were asked to recall if vaccine were given to her child.
According to the WHO guideline [ 1 ], “complete or full immunization” coverage is defined as a child that has received one dose of BCG, three doses of pentavalent, pneumococcal conjugate (PCV), oral polio vaccines (OPV); two doses of Rota virus and one dose of measles vaccine. We recoded each variable (vaccinations) as “0” and “1” for children who didn’t take the recommended doses and those who took, respectively, on the basis of the reports of mothers and information in the child vaccination card. Then we added all “0” and “1”s and labeled the total as “Immunization status”. The immunization status was recoded as “1” if the child had received all the recommended doses of all vaccinations and categorized as “full immunization” or “0” if the child had missed one or more doses of vaccinations and categorized as “Incomplete immunization”.
Statistical analysis
Descriptive statistics were used to describe the level of full immunization coverage by socio-demographic characteristics. Bivariate and multivariable logistic regression analyses were conducted to identify the determinants of full immunization. Logistic regression was chosen because our dependent variable was dichotomous (i.e., 0 and 1). Variables in bivariable logistic regression analysis with p -values less than 0.2 were entered into the multivariable analysis. Adjusted odds ratio (AOR) and 95% confidence Interval (CI) were used to assess the strength of associations between the outcome and the independent variables. The threshold for statistical significance was set at p < 0.05. The whole analysis was performed using STATA version 15.0.
Maternal and child socio-demographic characteristics
A total of 1,909 women with children aged 12–23 months were included in the final analysis. The majority (79.2%) women were rural dwellers and 61.1% of them had no formal education. The median age of the women was 28 (IQR: 24–33) years, and half of them were aged between 25 and 34 years; 47.3 and 31.5% were Muslims and Orthodox Christians, respectively. The poorest wealth quintile accounted for 34.3% of the participants the majority (93.5%) whom married, and about half (51%) of the children were male (Table 1 ).
Immunization coverage in Ethiopia
In this study the overall full immunization coverage was 38.3% (95% CI: 36.7 41.2) according to the Ethiopian EPI schedule. Vaccine specific coverage for Pentavalent 3, OPV3, PCV3, Rota 2, and Measles were 56.1, 60.4, 51.9, 58, and 57.8%, respectively (Fig. 1 ). Full immunization coverage among rural dwellers was 31.7 and 66.6% in urban areas. Full immunization coverage was heterogeneous among Ethiopian administrative regions, ranging from 8.8% in Afar region to 86.8% in Addis Ababa (Table 2 ).

Vaccine specific immunization coverage among 12–23 month children in Ethiopia, 2016
Determinants of full immunization among children aged 12–23 months
In the bivariable logistic regression, maternal education, residence, household head, wealth, employment, sex of household head, ANC follow-up, and parity were significant at 0.2 p -value. In the multivariable logistic regression, only employment, residence, maternal education, wealth quintile, place of delivery, sex of household head, and ANC follow up were statistically significant at p -value of 0.05.
The odds of full immunization for rural women’s children decreased by 40% (AOR = 0.60, 95% CI: 0.43, 0.84) compared to those of urban dwellers. The odds of full immunization for the children of employed mothers were 1.62 (AOR = 1.62, 95% CI: 1.31, 2.0) times higher compared to those of unemployed mothers. The odds of full immunization of children whose mothers had primary (AOR = 1.38, 95% CI: 1.07, 1.78) and secondary (AOR = 2.19, 95% CI: 1.43, 3.36) school as well as diploma and above (AOR = 1.99, 95% CI: 1.09, 3.61) level of educational were higher than those of children whose mothers had no formal education. For women who had middle and rich wealth status the odds of full immunization of children were 1.44 (AOR = 1.44, 95% CI: 1.07, 1.94) and 1.65 (AOR = 1.65, 95% CI: 1.25, 2.19) times higher compared to those of poorer mothers. The odds of full immunization of children whose mothers had ANC follow ups during pregnancy were 2.79 (AOR = 2.79, 95% CI: 2.17, 3.59) higher than those of children whose mothers had no follow ups. For women who delivered in health facilities, the odds of full immunization of children were 1.76 (AOR = 1.76, 95% CI: 1.38, 2.24) times higher compared to those of children whose mothers delivered at home. The odds of full immunization of children whose household heads were female were 42% (AOR = 0.58, 95% CI: 0.44, 0.76) lower than those of their counterparts (Table 3 ).
This study revealed that the overall full immunization coverage of Ethiopia was 38.3%, much lower than the 86% Government report and less promising to meet the 2020 health sector transformation plan of 95% [ 8 , 23 ]. Vaccine specific full immunization coverage’s among children were 56.1% for Pentavalent third dose and 57.8% for Measles, below the Federal Ministry of Health 2015 report of 94% for both of them [ 8 ]. The possible reasons for the discrepancies between the national reports and this study might be spurious and false reports from health facilities.
This study also showed differences between full immunization and vaccine specific full dose coverage’s. The possible explanations for the variations might be the stock out of vaccines and the side effects of multiple injections. Furthermore as shown in the Table 2 , full immunization coverage was in Ethiopia highly varies among administrative regions, ranging from 8.8% in Afar to 86.8% in Addis Ababa. The possible reasons might be socio-demographic and health seeking behavior differences among regions. In addition, most of the regions with low full immunization coverage had weak health care systems which led to low uptake of vaccines. Moreover, some of the regions like Afar and Somalia had hard to reach areas are nomadic and pastoralist inhabitants with no permanent residence.
This finding of full immunization coverage was lower than those of studies conducted in Togo (63.7%), Cameroon (53.6%), Timor-Leste (52.6%), Uganda (52.5%), Coted’Ivoire (50.5%) DR Congo (49.8%), and Haiti (45.8%) [ 1 , 4 , 20 , 24 , 25 ]. It was higher than findings in Somalia (11.6%), Mauritania (35.3), Nigeria (33.2%), Chad (11.4%), and the Republic of Central Africa (17.3%) [ 25 , 26 ]. The possible explanations might be differences in study periods and number of vaccines Like PCV and Rota incorporated in the expanded program of immunization of Ethiopia. Health system differences among countries are also possible explanations for the observed differences. The full immunization coverage finding in this study was significantly higher than 2005 and 2011 EDHS reports of 19 and 24%, respectively [ 14 ]. This might be due to tremendous efforts of the Government to realize the millennium development goal of reducing child mortality from vaccine preventable diseases.
Maternal characteristics, residence, educational level, sex of household head, employment, wealth index, ANC follow up and place of delivery were factors associated with full immunization coverage among 12–23 months of age children. Rural residence was associated with lower full immunization of children compared to urban dwellings. This finding is in agreement with those of studies conducted in Arbaminch, Lay Armachio, and Jigijiga of Ethiopia, and Nigeria [ 9 , 13 , 14 , 17 ]. This might be due to less accessibility of health facilities to EPI and differences in awareness about immunization. Maternal educational status of primary school and above associated with an increased full immunization of children. This finding is in agreement with the results of previous studies conducted in Ethiopia, Togo, Arbaminch, and Southwest Ethiopia [ 14 , 17 , 27 , 28 , 29 ]. The full immunization of children with female household heads was lower compared to children who had male household heads. This might be because of high workload and family responsibilities women may not heed EPI schedules for children vaccination. This finding was supported by that of a study conducted in Togo [ 20 ]. The full immunization of children whose mothers had ANC follow ups was three times higher than that of children whose mothers had no follow ups. This is supported by the results of previous studies conducted in Togo and Ethiopia [ 10 , 12 , 20 , 30 ]. This might be because women who attend follow ANC may get counseling about child immunization in the postnatal period. The children of middle income and rich mothers were associated with higher full immunization than the children of poor mothers. This might be due to differences in child care practice, better health seeking behavior, and health care access. This finding was supported by studies conducted in Nigeria, Togo, and Southwest Ethiopia [ 9 , 12 , 14 , 20 , 22 , 29 ]. The children of women who delivered at health facilities were two times more likely to receive full immunization compared to those of women who had home delivery. This finding was concordat with those of studies in Nigeria and Ethiopia [ 9 , 17 , 20 , 22 , 30 ]. This might be due to the fact that some vaccines, like BCG and OPV 0 are often given immediately after birth at health facilities. The children of employed mothers were associated with increased fully immunization compared to those of unemployed ones. This might be due to better information access about disease preventions, like immunization.
Sine not all children had vaccination cards, information about immunization status had to be limited the mothers’ verbal responses which were found to be prone to recall bias. Besides, having been based on secondary data analysis, this survey could not assess factors relating to the supply side and health system.
Full immunization coverage in Ethiopia was significantly lower than the global target. Female household head and rural dwelling were negatively associated with full immunization. In contrast higher maternal education, employment, middle and rich economic status, ANC follow up, and delivery at health facility were positively associated with full immunization among 12–23 months old children. This suggests that improved health education and service expansion to remote areas are necessary to step immunization access.
Availability of data and materials
The datasets used during the current study is available from the corresponding author on reasonable request.
Abbreviations
Antenatal care
Adjusted odds ratio
Bacilli Calamite Guerin
Diphtheria, pertussis, and tetanus
Enumeration area
Ethiopia Demography Health Survey
Expanded program of immunization
Interquartile range
Oral polio vaccine
Pneumococcal conjugate vaccine
Population and housing census
Reaching every district
South Nation’s Nationalities and Peoples
Sustainable outreach service
Vaccine preventable disease
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Acknowledgments
We would like to thank the Ethiopian Central Statistics Agency for providing me with all the relevant secondary data used in this study. Finally, we would like to thank all who directly or indirectly supported us.
We didn’t received external fund for this research.
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KST and MMS conceived the study, involved in the study design, data analysis, drafted the manuscript and critically reviewed the manuscript. Both authors read and approved the final manuscript.
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Tamirat, K.S., Sisay, M.M. Full immunization coverage and its associated factors among children aged 12–23 months in Ethiopia: further analysis from the 2016 Ethiopia demographic and health survey. BMC Public Health 19 , 1019 (2019). https://doi.org/10.1186/s12889-019-7356-2
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DOI : https://doi.org/10.1186/s12889-019-7356-2
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Pediatric Inpatient Immunizations: A Literature Review
Affiliations.
- 1 Divisions of Hospital Medicine and [email protected]
- 2 Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, California.
- 3 Children's Hospital Los Angeles, Los Angeles, California; and.
- 4 Infectious Diseases.
- PMID: 31209128
- DOI: 10.1542/hpeds.2019-0026
Context: Timely vaccine uptake in children remains suboptimal. Eliminating missed opportunities is key to increasing childhood immunization rates, and hospitalization offers another potential setting to vaccinate.
Objective: To better understand pediatric inpatient immunization programs, including vaccination rates of inpatients, parental and provider attitudes, barriers to vaccine delivery, and interventions to increase provision of inpatient vaccines.
Data sources: A search was conducted of PubMed, Embase, and Web of Science to identify articles and conference abstracts related to pediatric inpatient immunization.
Study selection: Inclusion criteria were studies published in English between January 1990 and January 2019 in which pediatric vaccination in the hospital setting was discussed. Findings from 30 articles and conference abstracts were summarized and organized by topic area.
Data extraction: Abstracts were screened for relevance, articles were read, and themes were identified.
Results: Children who are hospitalized have been shown to have lower immunization rates compared with the general population, with 27% to 84% of pediatric inpatients due or overdue for vaccines nationally when verified with official records. Unfortunately, little is done to catch up these children once they have been identified. Access to accurate vaccine histories remains a major barrier in inpatient immunization programs because providers frequently under document and parents over recall a child's vaccine status. Strategies identified to increase inpatient vaccination included creation of a multidisciplinary immunization team, educational interventions, visual reminders, catch-up vaccine plans, order sets, and nursing-driven screening. When offered inpatient vaccination, a majority of parents accepted immunizations for their children.
Conclusions: Hospitalization may provide an opportunity to augment vaccine uptake. Further research is needed to develop evidence-based strategies to overcome barriers to inpatient vaccination.
Copyright © 2019 by the American Academy of Pediatrics.
Conflict of interest statement
POTENTIAL CONFLICT OF INTEREST: Dr Pannaraj receives research funding from Pfizer and MedImmune; and Dr Mihalek and Ms Kysh have indicated they have no potential conflicts of interest to disclose.
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- Published: 16 July 2021
Understanding COVID-19 vaccine hesitancy
- Shingai Machingaidze 1 , 2 na1 &
- Charles Shey Wiysonge 2 , 3 na1
Nature Medicine volume 27 , pages 1338–1339 ( 2021 ) Cite this article
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A new study unpacks the complexities of COVID-19 vaccine hesitancy and acceptance across low-, middle- and high-income countries.
As of 29 June 2021, there had been more than 181 million reported infections with SARS-CoV-2 and nearly 4 million reported deaths from COVID-19 1 . In May 2020, the 73rd World Health Assembly issued a resolution recognizing the role of extensive immunization as a global public-health goal for preventing, containing and stopping transmission of SARS-CoV-2 2 . Globally, there are now more than 125 vaccine candidates, 365 vaccine trials ongoing, and 18 vaccines against COVID-19 approved by at least one country 3 . Published research carried out largely in high-income countries cites concerns about the safety of vaccines against COVID-19, including the rapid pace of vaccine development, as one of the primary reasons for hesitancy 4 , but data from low- and middle-income countries (LMICs) have been limited. In this issue of Nature Medicine , Solis Arce et al. present data that begin to address this research gap 5 .

The reluctance of people to receive safe and recommended available vaccines, known as ‘vaccine hesitancy’, was already a growing concern before the COVID-19 pandemic 6 . A framework developed from research done in high-income countries, called ‘the 5C model of the drivers of vaccine hesitancy’, provides five main individual person–level determinants for vaccine hesitancy: confidence, complacency, convenience (or constraints), risk calculation, and collective responsibility 7 , 8 . Promoting the uptake of vaccines (particularly those against COVID-19) will require understanding whether people are willing to be vaccinated, the reasons why they are willing or unwilling to do so, and the most trusted sources of information in their decision-making. Solis Arce et al. investigated these questions using a common set of survey items deployed between June 2020 and January 2021, across 15 studies carried out in Africa, South Asia, Latin America, Russia and the United States 5 .
Included in the analysis were seven studies in low-income countries (Burkina Faso, Mozambique, Rwanda, Sierra Leone and Uganda), five studies in lower-middle-income countries (India, Nepal, Nigeria and Pakistan) and one study in an upper-middle-income country (Colombia). The authors compare these findings with those from two countries at the forefront of vaccine research and development: Russia and the United States 5 . Overall, they found that the average acceptance rate across the full set of studies in LMICs was 80.3%, with lowest acceptance in Burkina Faso (66.5%) and Pakistan (66.5%); moreover, the acceptance rate in every sample from LMICs was higher than that of samples from the United States (64.6%) and Russia (30.4%) 5 . The data show that vaccine acceptance is explained mainly by an interest in personal protection against COVID-19, whereas concerns about side effects are the most common reasons for hesitancy, and health workers are the most trusted sources of guidance about vaccines against COVID-19 5 . It is, however, important to note that reported intentions may not always translate into vaccine uptake 9 .
Another survey was conducted by the Africa Centres for Disease Control and Prevention, in partnership with the London School of Hygiene and Tropical Medicine, between August and December 2020, in 15 African countries (Burkina Faso, Côte d’Ivoire, Democratic Republic of the Congo, Ethiopia, Gabon, Kenya, Malawi, Morocco, Niger, Nigeria, Senegal, South Africa, Sudan, Tunisia and Uganda) 10 . Again, it was found that the majority of respondents in Africa (79%) would be vaccinated against COVID-19 if it were deemed safe and effective 10 . Perhaps it may be that lived experience in LMICs, where many vaccine-preventable infectious diseases are still causing thousands of deaths annually, results in higher perceived need for or value of vaccines. In contrast, high-income countries have successfully eliminated or eradicated numerous vaccine-preventable diseases and, as a consequence, many people, including medical professionals, have not seen the devastating effects of these diseases in their respective countries. This could lead to complacency, altered risk calculations and limited collective responsibility about vaccination decision-making.
With the wide availability of smartphones, more people can now access the internet and social media in LMICs. Although this can be a great tool for self-education, which is a key component of vaccination decision-making, it also presents several challenges in the form of misinformation (including ‘anti-vaxx’ messaging) and incomplete information, as well as inconsistent and complicated scientific information that may be difficult to understand.
The reasons for COVID-19 vaccine acceptance and hesitancy remain complex. As new SARS-CoV-2 variants emerge, adding further complexity 11 , and new vaccines come to the market, it will be important to maintain a delicate balance in communicating what is known and acknowledging the uncertainties that remain. Researchers and pharmaceutical manufacturers should be as forthcoming as possible, with research data on vaccines against COVID-19 made readily available. International medical journals should ensure that the use of ‘expedited reviews’ does not compromise the robustness of the peer-review process of key publications on the safety and efficacy of vaccines, or related research findings. Governments should be transparent about their COVID-19 response programs and vaccine availability and should disclose how key decisions are being made. Reporting of adverse events after immunization is a key component of monitoring the implementation of vaccination programs, and although it is important for these events to be documented and reported, intensive media coverage may also discourage people from being vaccinated. The media should therefore report in a responsible and transparent manner, providing clear and unbiased information to its audiences. Finally, people using the internet and social media (including scientists and clinicians) should do so responsibly to avoid spreading falsehoods or using language that could be misinterpreted and could thereby potentially add to vaccine hesitancy.
Although issues of vaccine-distribution equity remain a considerable challenge for LMICs that require urgent intervention 12 , the lag in the rollout of vaccines against COVID-19 in these regions does present a window of opportunity for addressing issues of hesitancy. The findings from Solis Arce et al. 5 suggest that prioritizing distribution of vaccines to LMICs is justified not only on equity grounds but also on the expectation of higher marginal returns in maximizing global coverage at a faster rate 4 . The world shares a collective responsibility in fighting this pandemic; therefore, continued research on COVID-19 vaccine acceptance and hesitancy should be a priority. Such research should then be used to inform contextualized campaigns and information-sharing that will ultimately result in increased confidence in and uptake of available vaccines.
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These authors contributed equally: Shingai Machingaidze, Charles Shey Wiysonge.
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European and Developing Countries Clinical Trials Partnership, Africa Office, Cape Town, South Africa
Shingai Machingaidze
School of Public Health and Family Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa
Shingai Machingaidze & Charles Shey Wiysonge
Cochrane South Africa, South African Medical Research Council, Cape Town, South Africa
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Reactogenicity Following Receipt of mRNA-Based COVID-19 Vaccines
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- Research Letter Asymptomatic and Symptomatic SARS-CoV-2 Infections After BNT162b2 Vaccination in a Routinely Screened Workforce Li Tang, PhD; Diego R. Hijano, MD, MSc; Aditya H. Gaur, MD, MBBS; Terrence L. Geiger, MD, PhD; Ellis J. Neufeld, MD, PhD; James M. Hoffman, PharmD, MS; Randall T. Hayden, MD
- Original Investigation Effect of 2 Inactivated SARS-CoV-2 Vaccines on Symptomatic COVID-19 Infection in Adults Nawal Al Kaabi, MBBS; Yuntao Zhang, PhD; Shengli Xia, BSc; Yunkai Yang, MSc; Manaf M. Al Qahtani, MD; Najiba Abdulrazzaq, MBBS; Majed Al Nusair, MD; Mohamed Hassany, MD; Jaleela S. Jawad, MBBS; Jehad Abdalla, MBBS; Salah Eldin Hussein, MBBS; Shamma K. Al Mazrouei, MBBS; Maysoon Al Karam, MBBS; Xinguo Li, MSc; Xuqin Yang, MSc; Wei Wang, MSc; Bonan Lai, MSc; Wei Chen, MSc; Shihe Huang, PhD; Qian Wang, MSc; Tian Yang, BSc; Yang Liu, MSc; Rui Ma, MSc; Zaidoon M. Hussain, MD; Tehmina Khan, MD; Mohammed Saifuddin Fasihuddin, BSc; Wangyang You, BSc; Zhiqiang Xie, MSc; Yuxiu Zhao, MSc; Zhiwei Jiang, PhD; Guoqing Zhao, PhD; Yanbo Zhang, MSc; Sally Mahmoud, PhD; Islam ElTantawy, BSc; Peng Xiao, MSc; Ashish Koshy, MSc; Walid Abbas Zaher, PhD; Hui Wang, BSc; Kai Duan, PhD; An Pan, PhD; Xiaoming Yang, MD
In December 2020, 2 mRNA-based COVID-19 vaccines (Pfizer-BioNTech and Moderna) were granted Emergency Use Authorization by the US Food and Drug Administration as 2-dose series and recommended for use by the Advisory Committee on Immunization Practices. 1 - 3 In late February 2021, the US Food and Drug Administration granted Emergency Use Authorization for a third COVID-19 vaccine, a single-dose adenovirus vector-based vaccine from Janssen (Johnson & Johnson).
In clinical trials of the mRNA-based 2-dose vaccines, participants reported local and systemic reactions (reactogenicity). 4 , 5 Frequently reported reactions included injection site pain, fatigue, and headache; greater reactogenicity was reported following the second dose. 4 , 5 Continued monitoring of reactogenicity of COVID-19 vaccines outside of clinical trial settings may provide additional information for health care practitioners and the public about transient local and systemic reactions following COVID-19 vaccination.
V-safe Active Surveillance System
To facilitate rapid assessment of COVID-19 vaccines, in 2020, the Centers for Disease Control and Prevention (CDC) established v-safe, a new active surveillance system for collecting near–real-time data from COVID-19 vaccine recipients in the US. V-safe participants voluntarily self-enroll and receive periodic smartphone text messages to initiate web-based health surveys from the day of vaccination (day 0) through 12 months after the final dose of a COVID-19 vaccine. 6 From day 0 through day 7 after each vaccine dose, participants are asked questions about solicited local and systemic reactions (eg, injection site pain, fatigue, headache). These solicited reactions do not include allergic reactions or anaphylaxis; however, v-safe does allow participants to enter free-text information about their postvaccination experience and asks about adverse health events (eg, received medical care). Medically attended events are followed up on through active telephone outreach; future analyses will address these adverse vaccine experiences. This report describes information on solicited local and systemic reactogenicity reported to v-safe on days 0 to 7 after each dose of vaccine from December 14, 2020, through February 28, 2021. Responses were limited to individuals who were vaccinated by February 21, 2021, to allow a 7-day reporting period after the day of vaccination. Preliminary data from v-safe through January 13, 2021, have been previously reported. 7 This activity was reviewed by the CDC and was conducted consistent with applicable federal law and CDC policy (see Additional Information).
Self-reported Local and Systemic Reactions Among V-safe Participants
By February 21, 2021, more than 46 million persons received at least 1 dose of an mRNA-based COVID-19 vaccine. 8 A total of 3 643 918 persons were enrolled in v-safe and completed at least 1 health survey within 7 days following their first vaccine dose; 1 920 872 v-safe participants reported receiving a second vaccine dose and completed at least 1 daily health survey within 7 days following the second dose. Solicited local and systemic reactions during days 0 to 7 after each dose were assessed.
Most v-safe participants reported an injection site reaction (dose 1: 70.0%; dose 2: 75.2%) or a systemic reaction (dose 1: 50.0%; dose 2: 69.4%) during days 0 to 7 after vaccination ( Table ). The most frequently reported solicited local and systemic reactions after the first dose of COVID-19 vaccine were injection site pain (67.8%), fatigue (30.9%), headache (25.9%), and myalgia (19.4%). Reactogenicity was substantially greater after the second dose for both vaccines, particularly for systemic reactions, including fatigue (53.9%), headache (46.7%), myalgia (44.0%), chills (31.3%), fever (29.5%), and joint pain (25.6%).
A greater percentage of participants who received the Moderna vaccine, compared with the Pfizer-BioNTech vaccine, reported reactogenicity; this pattern was more pronounced after the second dose ( Table ). When stratified by age (<65 vs ≥65 years), differences in reactogenicity by vaccine remained consistent with overall findings (data not shown). Local and systemic reactions were less commonly reported by v-safe participants 65 years and older compared with those younger than 65 years, but greater reactogenicity after the second dose was observed for both age groups (eFigure in the Supplement ). For both doses of both vaccines, the percentage of v-safe participants who reported local and systemic reactions was highest on day 1 after vaccination and declined markedly through day 7.
The frequency of reported reactions was generally consistent with results observed in clinical trials. 4 , 5 Data from millions of v-safe participants indicate that injection site pain is common after both the first and second doses of either mRNA-based vaccine. Systemic reactions, including fatigue, headache, myalgia, chills, fever, and joint pain, occurred in participants after the first dose, although they were more frequently reported after the second dose among both Pfizer-BioNTech and Moderna vaccine recipients. Persons 65 years and older reported less reactogenicity than younger persons. Limitations of v-safe include voluntary participation via an opt-in smartphone-based system that includes less than 10% of vaccinated persons.
Although local and systemic reactions are expected and often transient, they may have the most immediate influence on patients’ perceptions of the vaccination experience. Setting expectations with patients may alleviate some of the potential anxiety elicited by postvaccination reactogenicity. Clinicians should counsel vaccine recipients that these solicited local and systemic reactions are most commonly reported during the first day following their second dose; a short period before symptom resolution can be expected. 9
Corresponding Author: Johanna Chapin-Bardales, PhD, MPH, Centers for Disease Control and Prevention, 1600 Clifton Rd, Atlanta, GA 30329 ( [email protected] ).
Published Online: April 5, 2021. doi: 10.1001/jama.2021.5374
Conflict of Interest Disclosures: Drs Chapin-Bardales, Gee, and Myers reported receiving nonfinancial technical support to build and maintain the v-safe infrastructure for data capture and messaging to participants from Oracle during the conduct of the study.
Disclaimer: The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the US Centers for Disease Control and Prevention (CDC). Mention of a product or company name is for identification purposes only and does not constitute endorsement by the CDC.
Additional Contributions: We thank investigators from the CDC COVID-19 Response Team and the CDC v-safe team, members of the Oracle v-safe development team, and v-safe participants who contributed to these data.
Additional Information: See eg, 45 CFR part 46.102(l)(2) ; 21 CFR part 56 ; 42 USC §241(d) ; 5 USC §552a ; 44 USC §3501 et seq .
eFigure. Local and systemic reactions to COVID-19 mRNA-based vaccines by age, dose, and day since vaccination—CDC v-safe surveillance system, December 14, 2020, to February 28, 2021
See More About
Chapin-Bardales J, Gee J, Myers T. Reactogenicity Following Receipt of mRNA-Based COVID-19 Vaccines. JAMA. 2021;325(21):2201–2202. doi:10.1001/jama.2021.5374
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Open Access
Peer-reviewed
Research Article
Attitudes on voluntary and mandatory vaccination against COVID-19: Evidence from Germany
Roles Conceptualization, Formal analysis, Writing – original draft, Writing – review & editing
Affiliation DIW Berlin / SOEP, Berlin, Germany

* E-mail: [email protected] (CSP); [email protected] (CS)
Affiliation Karlsruhe Institute of Technology, Karlsruhe, Germany
Affiliations DIW Berlin / SOEP, Berlin, Germany, Freie Universität Berlin, Berlin, Germany
- Daniel Graeber,
- Christoph Schmidt-Petri,
- Carsten Schröder

- Published: May 10, 2021
- https://doi.org/10.1371/journal.pone.0248372
- Reader Comments
Several vaccines against COVID-19 have now been developed and are already being rolled out around the world. The decision whether or not to get vaccinated has so far been left to the individual citizens. However, there are good reasons, both in theory as well as in practice, to believe that the willingness to get vaccinated might not be sufficiently high to achieve herd immunity. A policy of mandatory vaccination could ensure high levels of vaccination coverage, but its legitimacy is doubtful. We investigate the willingness to get vaccinated and the reasons for an acceptance (or rejection) of a policy of mandatory vaccination against COVID-19 in June and July 2020 in Germany based on a representative real time survey, a random sub-sample (SOEP-CoV) of the German Socio-Economic Panel (SOEP). Our results show that about 70 percent of adults in Germany would voluntarily get vaccinated against the coronavirus if a vaccine without side effects was available. About half of residents of Germany are in favor, and half against, a policy of mandatory vaccination. The approval rate for mandatory vaccination is significantly higher among those who would get vaccinated voluntarily (around 60 percent) than among those who would not get vaccinated voluntarily (27 percent). The individual willingness to get vaccinated and acceptance of a policy of mandatory vaccination correlates systematically with socio-demographic and psychological characteristics of the respondents. We conclude that as far as people’s declared intentions are concerned, herd immunity could be reached without a policy of mandatory vaccination, but that such a policy might be found acceptable too, were it to become necessary.
Citation: Graeber D, Schmidt-Petri C, Schröder C (2021) Attitudes on voluntary and mandatory vaccination against COVID-19: Evidence from Germany. PLoS ONE 16(5): e0248372. https://doi.org/10.1371/journal.pone.0248372
Editor: Valerio Capraro, Middlesex University, UNITED KINGDOM
Received: October 19, 2020; Accepted: February 25, 2021; Published: May 10, 2021
Copyright: © 2021 Graeber et al. This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: Our analyses rely on the German Socio-Economic Panel (SOEP), an independent scientific data infrastructure established in 1984. We, as users, cannot send the data to the journal and make them publicly available, as this is against SOEP's statutes (and most likely against the statutes of all providers of micro data). However, this should not be a hurdle, as researchers from scientific institutions around the globe can access the data (free of costs) once they have signed a user contract. The scientific use file of the SOEP with anonymous microdata is made available free of charge to universities and research institutes for research and teaching purposes. The direct use of SOEP data is subject to the provisions of German data protection law. Therefore, signing a data distribution contract is the single precondition for working with SOEP data. The data distribution contract can be requested with a form which can be downloaded from: http://www.diw.de/documents/dokumentenarchiv/17/diw_01.c.88926.de/soep_application_contract.pdf .
Funding: The data collection of the SOEP-CoV Study was financially supported by the German Federal Ministry of Education and Research. We acknowledge support by the KIT-Publication Fund of the Karlsruhe Institute of Technology. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
Introduction
Great efforts have been made worldwide to develop a vaccine against COVID-19. When we first drafted this article, in October 2020, 35 different potential vaccines were in clinical trials and 145 were still in the pre-clinical stage. In February 2021, several vaccines have been approved in many countries and are being rolled out, 74 are in clinical trials, and 182 are in the pre-clinical stage [ 1 ].
These developments are very encouraging, as a wide availability of vaccines is seen by many as a prerequisite for a return to a “normal” pre-COVID-19 type of social and economic life. With the growing availability of vaccines comes the hope that coercive measures such as restrictions on international trade, contact restrictions, and travel bans, etc., which cause enormous economic and social costs, may soon be removed and will not need to be reimplemented.
Of course, any vaccine is only an effective contribution to a return to normal life if a sufficiently high number of people are actually vaccinated, yielding herd immunity. If so, vaccination secures a public good: protection from COVID-19 for everyone. From a microeconomic perspective, this raises a well-known problem, free-riding: If the vaccination is freely available but not obligatory, then citizens’ individual decisions determine the extent to which this public good is made available. In order to make that decision, they will weigh their own costs and benefits. These costs include the time sacrificed, physical unpleasantness, possible side effects of a vaccination, etc. The benefits to a particular individual are primarily, but not necessarily exclusively, the reduction in risk to that person’s own health or material well-being. From a welfare perspective, if individuals do not take into account the positive externalities on third parties that their own vaccination triggers, there will be an undersupply of the public good. Following [ 2 , 3 ], individuals’ utility function may also include other-regarding preferences and hence yield a direct benefit from contributions to a public good. In our context, people could therefore benefit from a ‘warm glow of vaccinating’, because by vaccinating themselves they also reduce the risks of others. But even so there is certainly no guarantee that the social optimum will be reached [ 4 ] or that a sufficiently high number of people will freely choose to get vaccinated.
It is frequently argued that vaccination should be made mandatory because of the free-rider problem [ 5 ]: While vaccinated individuals have incurred private costs in terms of discomfort or money and receive the private benefit of a reduced risk of getting the disease, the major collective benefit, the reduced incidence of disease, is public. If enough other people produce the public benefit, and the circulation of the virus decreases accordingly, an individual might rationally decide to free-ride on others’ decisions. A policy of mandatory vaccination would prevent this.
[ 6 ] argue that such a policy would not be necessary: “If vaccinations are perfect, then if one is vaccinated he or she does not care whether others are vaccinated, so there is no longer any public good problem” ([ 6 ], p. 70). Hence there would not be a case in favor of mandatory vaccination, as under such a policy, individuals who would have favored not to be vaccinated are made worse off, while those who anyway would get vaccinated are not better off.
However, by definition, ‘perfect’ vaccination means that everyone vaccinated is perfectly immune [ 6 ]. In the current situation, it can neither be taken for granted that a perfect vaccination is being or will be provided soon, nor that everyone who wants to also will have the possibility to be vaccinated (both financially and in terms of health). If perfect vaccination is not feasible, however, mandatory vaccination is not dominated by a laissez faire solution [ 6 ].
Extensions of this theoretical public good analysis emphasize the relevance of behavioral aspects not typically considered in classical models. The empirical literature also highlights a number of factors that matter for vaccine uptake. For instance [ 7 ], show that social norms matter for an individual’s willingness to get a vaccination and that such norms can suppress vaccine uptake even in the presence of frequent disease outbreaks. Further [ 8 ], show that the design of public vaccination policies should also take intergroup interactions into account. Other-regarding preferences can explain voluntary vaccination uptake, as argued by [ 9 ]. For example [ 10 ], show that the presence of individuals who cannot get vaccinated, like babies and the elderly, increases the willingness to get vaccinated. The static model in [ 6 ] also does not reflect interactive processes [ 9 , 11 ]. show that vaccination is the individually best response until a certain vaccination rate is reached in the population and becomes a social dilemma only from this vaccination rate until herd immunity is maximized. Communicating the social benefits of vaccination can have positive effects, particularly when this protects vulnerable groups, but it can also invite free-riding [ 12 ]. Those people who cannot get vaccinated themselves for medical reasons are particularly vulnerable: they cannot protect themselves even if they wanted to and, hence, depend on their fellow citizens to protect them by preventing the spread of the virus through their vaccination. Children, too, need to be considered separately. Since they cannot give informed consent to a voluntary vaccination themselves, they might have to be protected from their parents (who might be unwilling to get them vaccinated) in case of particularly serious diseases (see [ 13 , 14 ]).
There is, in summary, hope that the public goods problem may be overcome, as social and behavioral science offers a wide array of potential policy options to influence people’s perceptions and reactions to the pandemic (for an extensive up-to-date overview, see [ 15 ]). It is not clear, however, how the research on well-established vaccines carries over to the current pandemic, and recent developments seem to indicate that the willingness to get vaccinated against the novel coronavirus is currently rather low. We therefore chose to investigate two fundamental questions at the opposite extremes of the spectrum of policy options: would a sufficient number of people voluntarily undergo vaccination to achieve herd immunity? Or would a mandatory vaccination against COVID-19 be acceptable to achieve herd immunity?
A legal duty to be vaccinated against COVID-19 could be an alternative to other coercive measures if one assumes that a high-risk, unregulated, laissez faire approach is not a realistic policy option: it seems irresponsible to lift all restrictions because the virus would soon spread through the entire population. Coercive measures of some kind therefore seem inevitable. Mandatory vaccination could be preferable to other coercive measures, provided the interference with bodily integrity would be considered less socially costly in the long run than the effects of prolonged lockdowns. Emotions run high where vaccination policies are concerned, but because mandatory vaccination might become a realistic scenario, it is worth investigating what the general population thinks about such a policy.
It is important to emphasize that a legal duty to vaccinate against COVID-19 would not imply a legal (or even moral) duty to vaccinate against other diseases. The novel coronavirus is a special case in many respects: In contrast to influenza, for example, the population does not have a background immunity from past infections. In addition, many infected people do not show symptoms (a recent meta-study estimates this to be one in six infected [ 16 ]) and, hence, cannot protect others from being infected through voluntary self-quarantining. Thus, people with COVID-19 represent a much higher risk of infection for others than, for example, people who come down with influenza, assuming that these would normally stay at home. Therefore, a vaccination against COVID-19 is much more important from the social perspective than e.g. a vaccination against influenza: not for self-protection, but to protect other people from unintentional infection. Although classic liberal positions (cf. [ 17 ]) would reject a paternalist legal obligation to protect oneself through vaccination, they plausibly would favor a policy of mandatory vaccination in the case of COVID-19 to protect others from being harmed. In modern philosophical discussions, even some libertarians are in favor of mandatory vaccination against serious diseases for similar reasons (see [ 18 ] and for an overview [ 19 ]).
Though there are philosophical reasons supporting a policy of mandatory vaccination, we want to emphasize that we are not advocating it as a concrete policy option for Germany at this moment. Our aim is to understand whether the general public would consider such a policy acceptable, or which sections of the population, and why. To this end, we study the willingness to get vaccinated and the acceptance of a policy of mandatory vaccination against COVID-19 in June and July 2020 in Germany. We use unique real time survey data from a sub-sample (SOEP-CoV) of the German Socio-Economic Panel (SOEP, see [ 20 ]). A set of questions about vaccination was part of the later stages of SOEP-CoV, an ongoing research project initiated in April 2020. This so-called ‘vaccination module’ included questions on the willingness to get vaccinated voluntarily and the acceptance of a policy of mandatory vaccination against COVID-19. In addition, individuals could indicate reasons for their preference regarding the second question. Using the rich data of the SOEP, pre-pandemic income, education, household context, personality, political preferences etc., which can be directly linked with SOEP-CoV, we are able to provide a detailed picture on who intends to get vaccinated and who does not.
The most important result of our study is that about 70 percent of adults in Germany would get vaccinated voluntarily against COVID-19 if a vaccine without significant side effects was available. Further, about half of adults in Germany are in favor, and half against, a policy of mandatory vaccination against COVID-19. The approval rate for mandatory vaccination is significantly higher among those who would get vaccinated voluntarily (around 60 percent) than among those who would not get vaccinated voluntarily (27 percent). However, 22 percent of the individuals would disapprove of both a voluntary and a mandatory vaccination and 8 percent can be characterized as ‘passengers’ (they are not willing to get vaccinated but do support a policy of mandatory vaccination, but they might not all be ‘free-riders’ in the standard sense). In this group, surprisingly, 86 percent state that, without a mandatory vaccination, too few individuals would get vaccinated and about 87 percent indicate that most people underestimate how dangerous COVID-19 is. In general, the willingness to get vaccinated is significantly lower for female, younger, and less educated respondents as well as those with lower income. A policy of mandatory vaccination is rejected with higher probability by women and favored by older people and those living in the eastern federal states.
Data, measures, and methods
Data: soep and soep-cov.
The German Socio-economic Panel (SOEP) is among the largest and longest-running representative panel surveys worldwide and is recognized for maintaining the highest standards of data quality and research ethics [ 20 ]. In 2020, the survey covers about 30,000 adults in 20,000 households. Since the same individuals and households participate in the study every year, life courses of the respondents can be tracked and intertemporal analyses can be carried out at the individual and at the household level. The data contain information on the respondents’ household situation, education, labor market outcomes, and health, among others (see [ 20 , 21 ]).
To better understand the effects of the corona pandemic, a special survey called SOEP-CoV was conducted within the framework of the SOEP, which consisted of a random sample of about 6,700 SOEP respondents, (see [ 21 , 22 ]). SOEP-CoV was surveyed in nine staggered tranches from early April to the end of July 2020 and collected data on the following topics: a) Prevalence, health behavior, and health inequality; b) Labor market and gainful employment; c) Social life, networks, and mobility; d) Mental health and well-being; and e) Social cohesion. Over time, some new question modules were introduced within these five thematic complexes. These included the ‘vaccination module’ (see questionnaires available under www.soep-cov.de/Methodik/ ).
Measures: Preferences toward vaccination against COVID-19
The ‘vaccination module’ went into the field with tranches 7 to 9, in June and July 2020, and covered a total of 851 persons aged 19 years and older. At that moment, major research efforts were being undertaken, but it was not clear whether any vaccine would actually be found. The module hence starts with a question on the hypothetical willingness to get vaccinated against COVID-19:
- “Let us assume that a vaccine against the novel coronavirus that is shown to have no significant side effects is found. Would you get vaccinated?” The response categories are ’Yes’, ’No’, and ‘no answer’. The module contains a further question about mandatory vaccination with the same response categories:
- “Would you be in favor of a policy of mandatory vaccination against the coronavirus?” In addition, the interviewees were asked about their reasons for or against a policy of mandatory vaccination. For this purpose, a filter was used to adapt the arguments according to the respondents’ answers to question (B). The arguments given were as follows:
Argument 1: Others’ willingness to get vaccinated without mandatory vaccination
- Against mandatory vaccination: “Enough people would get vaccinated even without a policy of mandatory vaccination.”
- In favor of mandatory vaccination: “Only with a policy of mandatory vaccination would enough people get vaccinated.”
Argument 2: Misperception of risks
- Against mandatory vaccination: “Most people overestimate the dangerousness of the virus.”
- In favor of mandatory vaccination: “Most people underestimate the dangerousness of the virus.”
Argument 3: Legitimacy of a policy of mandatory vaccinations in general
- Against mandatory vaccination: “A policy of mandatory vaccination is never permissible, even in the case of very dangerous diseases.”
- In favor of mandatory vaccination: “A policy of mandatory vaccinations would make sense also for less dangerous diseases.”
Argument 4: Other reasons (without listing these reasons explicitly)
The first three arguments are of particular relevance for political decision-making. Although there is quite a lot of research on the reasons people have not to get vaccinated themselves, there is much less research on what people think about policies of mandatory vaccinations, and up to present–at least to our knowledge–none on the application to the special case of the novel coronavirus. As the reasons for the individual decision need not carry over to the policy assessment, and given the previously discussed particularities of the coronavirus, we focused on factors that are both of theoretical importance and under discussion in the general public. It would be interesting, for instance, if many people did not have the intention to get vaccinated themselves, yet believed that enough other people would get vaccinated so that mandatory vaccination would not be required. Similarly, it would be surprising if people wanted to get vaccinated yet believed that others overestimated the dangerousness of the virus. Finally, we wanted to see whether people considered mandatory vaccinations potentially legitimate at all.
Sample selection, weighting, and item non-response
Since SOEP-CoV is a random sample from the SOEP population, the SOEP-CoV data 2020 can be linked with the regular SOEP data of previous years. Thus, attitudes toward vaccination against COVID-19 that were collected during the pandemic can be linked to the characteristics of the respondents before the outbreak of the pandemic (e.g., income or educational level). Since these characteristics were collected before the pandemic, they can be considered unaffected by the pandemic event and, hence, exogenous ( S1 File provides definitions of all dependent and independent variables used in the empirical analyses).
The response rate in the vaccination module was high. Altogether, only 4.58 percent of the 851 respondents did not answer the question about voluntary vaccination and 3.41 percent did not answer the question about mandatory vaccination. Of those who supported (objected to) mandatory vaccination, 0.26 (1.82) percent did not provide at least one motive in the follow-up question. Hence, bias from item non-response should be small and we did not correct for it. As the focal variables are coded dichotomously (yes = 1; no = 0), there was no need to remove outliers in them from the database.
To derive population-wide estimates, the SOEP-CoV data is equipped with frequency weights. The weighting of SOEP-CoV follows the standard weighting used in SOEP [ 23 , 24 ]. Based on the SOEP household weights, weights for all persons in the participating households were generated via a marginal adjustment step and corrected for selection effects. Furthermore, the data were corrected for the fact that some SOEP subsamples were excluded from the SOEP-CoV study from the outset. To address potential selection effects and adjust frequency weights accordingly, we followed the two-step procedure recommended in [ 25 ]:
- Step 1: Estimation of a logistic regression model where the dependent variable is a dummy variable indicating whether respondents belong to the working sample of tranches 7 to 9 (dummy is equal to one) or not (dummy is zero). All variables included in the following analyses serve as explanatory variables.
- Step 2: If at least one analysis variable shows a significant (i.e., p -value below 0.05) and at the same time meaningful effect (i.e., coefficient above 0.01) with respect to the assignment to the analysis population, a correction of the SOEP-CoV weights is performed by multiplying the frequency weights by the inverse estimated probability. In other words, multiplying the SOEP-CoV weights belonging to the analysis set by the inverse predicted probability yields the sought adjusted weight that can be used to calculate population statistics. In the present case, an adjustment using the following variables is indicated: Extraversion and whether respondents live in a household in which at least one household member was tested for COVID-19. Overall, selection on observables is very minor. Unless otherwise stated, our results are weighted with the adjusted probability weights.
Statistical framework
Since the vaccination questions are answered once by each respondent, our empirical strategy is between-person. Uni- and bivariate results for our focal variable, attitudes toward vaccination, are presented as weighted means or percentages. Assessments of differences in attitudes or characteristics between-groups rely on two-tailed t-tests, with statistical significance evaluated at p <0.01, p <0.05, and p <0.10 using the survey weights explained above. Our empirical strategy involves multiple between-group tests. This raises the question of whether a correction is necessary for multiple hypotheses testing. We do not implement such a correction because we seek to compare a certain attitude or characteristic between groups and not to draw, at the end of the test series, a concluding summary of all tests results.
Willingness to get vaccinated and attitudes toward a policy of mandatory vaccination
For the questions on voluntary vaccination (A) and mandatory vaccination (B), four groups in the population may be distinguished:
- Anti-vaccination: interviewees who would not get vaccinated voluntarily against the coronavirus and who also oppose a policy of mandatory vaccination.
- Anti-duty: interviewees who would get vaccinated voluntarily but oppose a policy of mandatory vaccination.
- Passengers: interviewees who would not get vaccinated voluntarily but are in favor of mandatory vaccination. We refer to this group as ‘passengers’ because they apparently want to see the public good of herd immunity provided by mandatory vaccination, yet would not voluntarily contribute to this good. Some of these passengers might be free-riders in the standard sense, trying to benefit from the decisions of others while not voluntarily contributing themselves, while others might not be able to get vaccinated for medical reasons. If mandatory vaccination were introduced, the first group, but not the second, would also get vaccinated, of course. Neither group would actually free-ride, but the first might initially have wanted to.
- Pro-vaccination: interviewees who would get vaccinated voluntarily and are also in favor of mandatory vaccination.
Overall, 70 percent of adults in Germany would voluntarily get vaccinated against the coronavirus, provided a vaccine without significant side effects was available ( Table 1 : groups 2 and 4). This value corresponds exactly to the results of [ 26 ]. From May till September 2020, the COVID-19 snapshot monitoring (COSMO) at the University of Erfurt showed relatively constant values of between 60 and 66 percent; it was only in April that it showed an exceptionally high value of 79 percent, and it has now decreased further (cf. [ 27 ], p. 76; an overview of previous studies on the willingness to get vaccinated in Germany is provided in S2 File .). Overall, these studies paint a consistent picture, with a slight decline in the willingness in the second half of 2020.
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https://doi.org/10.1371/journal.pone.0248372.t001
Approximately half of the interviewees are against, and half are in favor of, a policy of mandatory vaccination (against: 51%, groups 1 and 2, in favor: 49%, groups 3 and 4). These values, too, coincide almost exactly with those of the COSMO monitoring since May 2020 (cf. [ 27 ], p. 78), which in April showed an approval rate for mandatory vaccination of 73 percent, but later discontinued this question (till July 2020, and it has been decreasing since; see S2 File ). The agreement with a policy of mandatory vaccination is clearly higher, namely almost 60 percent (41/(41+29) = 0.59) among those who would get vaccinated voluntarily than with those who would not let themselves be vaccinated voluntarily, i.e. approximately 27 percent (8/(8+22) = 0.27).
Attitudes toward a policy of mandatory vaccination
The four groups differ noticeably in how they assess the arguments presented to them. This is shown in Table 2 , which gives the group-specific approval rate for each argument in combination with the p-values of t-tests in S3.1 Table in S3 File .
https://doi.org/10.1371/journal.pone.0248372.t002
Argument 1.
The groups differ markedly in how likely they think it is that others will get vaccinated. Among the two groups that are against a policy of mandatory vaccination, 56 percent of the ‘anti-vaccination’ group (who would not get vaccinated voluntarily) think that their fellow citizens would get vaccinated sufficiently frequently such that mandatory vaccinations would not be necessary. Almost 80 percent of the ‘anti-duty’ group (the members of which would get vaccinated voluntarily) think the same. Among the two groups that are in favor of mandatory vaccination, 85 percent of the ‘passengers’ (who would not voluntarily get vaccinated) think that the others would not voluntarily get vaccinated either, as do slightly more than 90 percent of the ‘pro-vaccination’ group (who would also get vaccinated voluntarily).
Argument 2.
These results run in parallel with the assessment of the dangerousness of the virus. Even though the analysis is not causal, we can see that about 50 percent of the ‘anti-vaccination’ group and 30 percent of the ‘anti-duty’ group think that most people overestimate the dangerousness of SARS-CoV-2. Exactly the opposite, that most people underestimate the dangerousness, is believed by nearly 90 percent of the ‘passenger’ group and by slightly more than 80 percent of the ‘pro-vaccination’ group. Summarizing the numbers differently, one could say that groups 2 and 4, who would voluntarily get vaccinated, probably have similar opinions about whether their fellow citizens correctly assess the danger posed by the virus. About 80 percent of the members of the ‘pro-vaccination’ group think that most people underestimate the danger. Of the members of the ‘anti-duty’ group, we only know with certainty that 30 percent of them believe that most people overestimate the danger–we do not know, however, how the remaining 70 percent are divided between ’underestimate’ and ’correctly estimate’. The difference between the corresponding values for groups 1 and 3 is significantly higher.
Looking at arguments 1 and 2, we may conclude that there is a high level of disagreement among the population about the dangerousness of the virus. This disagreement probably explains why people have such different attitudes toward getting vaccinated and toward the necessity (or not) of a policy of mandatory vaccination.
The position of the group of the ‘passengers’ is hard to understand. On the one hand, they favor a policy of mandatory vaccination, presumably because, as they do believe, the dangerousness of the virus is often underestimated. On the other hand, they probably assume that they themselves do not underestimate that dangerousness, but nevertheless would not get vaccinated voluntarily. One reason for this could be their medical condition: they might be willing but unable to get vaccinated for medical reasons. If so, they would not be trying to free-ride. It is unclear, however, how much weight the appeal to such a hypothetical medical contraindication should have, given that at the time of the interviews, no vaccine was even available. Some, but not all, of the ‘passengers’ are probably free-riders in the standard sense.
Argument 3.
Approximately 40 percent of both the ‘anti-vaccination’ group and the ‘anti-duty’ group agree with the statement that a mandatory vaccination is never permissible, not even with very dangerous diseases. Since these two groups reject mandatory vaccination against COVID-19, this means that for the remaining 60 percent of the group, mandatory vaccination may well be permissible–but apparently only for diseases that they would have to consider as even more dangerous than COVID-19. Conversely, well over 60 percent of the ‘passenger’ group and just over 70 percent of the ‘pro-vaccination’ group agree with the statement that a policy of mandatory vaccination would also make sense for less dangerous diseases. In combination with the results for argument 2, these two groups could therefore believe that their fellow citizens also underestimate the danger of such other diseases. It is interesting to note that, overall, people in Germany estimate the probability that the novel coronavirus will cause a life-threatening disease within the next twelve months to be high (cf. [ 20 ]). This probability is around 25 percent across our four groups. In group 1 it is 20 percent, in group 2 around 27 percent, in group 3 it is 30 percent and in group 4 it is 25 percent (see Table 3 ).
https://doi.org/10.1371/journal.pone.0248372.t003
Other reasons (which were not further broken down in the questionnaire for capacity reasons) are important primarily among those respondents who would not themselves get vaccinated and also oppose mandatory vaccination. Although questions (A) and (B) explicitly assume that a vaccine would not have any significant side effects, this could be due to a deeper skepticism about vaccination, which we hope to be able to explore in future research (on ’vaccine denialism’ see [ 28 ]).
Characteristics of the ‘anti-vaccination’, ‘anti-duty’, ‘passenger’, and ‘pro-vaccination’ groups
Description of the individual characteristics of the groups..
We would like to know in more detail who is in favor of a policy of mandatory vaccination against COVID-19 and who is opposing it, as well as what the socio-economic characteristics of those who would get vaccinated and of those who would not are. Table 3 shows how the four groups defined above differ across various socio-demographic characteristics (measured before the pandemic), personality (measured before the pandemic), health (before and during the pandemic), and political orientation (measured before the pandemic). Statistical t-tests for the significance of differences in characteristics between groups are shown in S3.2 Table in S3 File assuming equal variances across groups. S3.3 Table in S3 File provides supporting evidence: tests for equality of variance across groups provides support for this assumption in about 90% of the cases, and as S3.4 Table in S3 File . shows, relaxing the equality of variances assumption does not change our conclusions.
Socio-demographic characteristics . Almost 60 percent of the ‘anti-vaccination’ group are female, they are on average 48 years old, 12 percent of them have a university degree and their monthly net household income in 2019 averaged just under EUR 2,800. Around 27 percent have children under 16 and around 17 percent live in the eastern German states. ‘Passengers’ do not differ in their characteristics statistically significantly from this group. The members of the ‘anti-duty’ group, by contrast, are much more likely to be male and more often have a university degree. In comparison to the ‘anti-vaccination’ group, the members of the ‘pro-vaccination’ group are also more often male and older, and are also more likely to have a university degree. In particular, older interviewees are more likely to be in groups that favor mandatory vaccination and persons with a university education in groups comprising those who would get vaccinated voluntarily.
Personality traits . SOEP collects the personality traits of the respondents using a battery of questions that measure the five dimensions of the so-called ’Big Five’ [ 29 ]. The Big Five are the five most important groups of character traits in personality research: ’openness’, ’conscientiousness’, ’extraversion (sociability)’, ’tolerance’, and ’neuroticism’. Furthermore, risk attitude is surveyed. We see that members of the ‘anti-vaccination’ group tend to be more sociable but less open than the other groups. Their willingness to take risks is similar to that of the members of the ‘anti-duty’ and of the ‘pro-vaccination’ groups, but is significantly higher than that of ‘passengers’. Members of the ‘anti-duty’ group are particularly unsociable compared to the other groups, but open to new experiences. The ‘passengers’ are, like the members of the ‘pro-vaccination’ group, less neurotic. They are particularly tolerable and the least willing to take risks of the four groups.
Health . As far as the health of those surveyed is concerned, statistically significant differences are only evident in the number of illnesses: Members of the ‘anti-vaccination’ group have significantly fewer risk diseases than ‘passengers’ and members of the ‘pro-vaccination’ group. ‘Anti-duty’ members, on the other hand, have significantly fewer diseases than the ‘passengers’. Thus, overall, it may be said that those who refuse a policy of mandatory vaccination have fewer risk diseases at the time of the survey. There are no differences between the groups in terms of whether a member of the respondent’s household has already undergone a test for an infection with corona. It should be noted, however, that the number of cases of those tested for an infection is comparatively small.
Political orientation . As far as the political orientation of the respondents is concerned, no systematic significant differences between the four groups are identified. Only the members of the ‘anti-vaccination’ group seem to be positioned somewhat more to the right in the party spectrum than the members of the ‘anti-duty’ group.
Multivariate description of the characteristics of the four groups.
The differences and similarities with regard to group composition described above always refer to a single characteristic, i.e. they are univariate. Additionally, the relationships between individual characteristics of the respondents–after taking other characteristics into account–and their attitude toward mandatory or voluntary vaccination are explained below using a multivariate model (logistic estimation; see Eq ( 1 )). The dependent variable is either an indicator that describes the respondent’s own willingness to get vaccinated voluntarily (value 1 = yes; 0 = no; Table 4 ) or an indicator (value 1 = yes; 0 = no) that describes whether the respondents favors a policy of mandatory vaccination ( Table 5 ). As our interest is the explanation of data structures, we do not use survey weights in the multivariate analysis.
https://doi.org/10.1371/journal.pone.0248372.t004
https://doi.org/10.1371/journal.pone.0248372.t005
With regard to the willingness to voluntarily get vaccinated ( Table 4 ), some significant differences in socio-demographic characteristics are observed. If all other characteristics are kept constant, the willingness to vaccinate is about 10 percentage points lower in women than in men. It is positively associated with age (0.4 percentage points per year of life), education (13 percentage points if respondents have a university degree compared to the other education categories), and household income (2.5 percentage points per 1,000 euros). The personality traits of the Big Five do not correlate with the respondents’ willingness to vaccinate; only openness is slightly positively associated with the willingness to vaccinate. In the health block, there is also only one significant variable that correlates with the willingness to get vaccinated: The higher the respondents estimate the probability that the virus could trigger a life-threatening disease in them, the more willing they are to be vaccinated.
A policy of mandatory vaccination ( Table 5 ) is also rejected with higher probability by women, but favored by older people and those living in the eastern federal states, ceteris paribus . Approval is negatively associated with neuroticism, i.e. emotional instability, and positively associated with the subjective probability of contracting life-threatening COVID-19.
The tables presenting the logit estimations include an initial model diagnostic: the Pseudo- R 2 . In S4 File , we present two additional model diagnostics: First, the linktest for both logit models does not find any evidence for model misspecifications. Second, a receiver operator characteristic (ROC) analysis provides evidence that the predictive power of our two models is acceptable. In addition, to assess multicollinearity, we have computed variance inflation factors (VIF) in S5 File . As a rule of thumb, a variable whose VIF values exceeds 10 may merit further investigation. In both regressions, the VIF of none of the explanatory variable exceeds 7.7 and the average VIF over all variables is below 2.1. It should also be noted that the two separate logit models do not model correlation and heteroscedasticity between the two outcomes (vaccinate voluntarily or obligatorily). Hence, in S6 File , as a robustness check, we have estimated a multivariate probit model using Stata’s mvprobit command that relies on simulated maximum likelihood [ 30 ]. S6.1-S6.6 Tables in S6 File compare the coefficients of the multivariate probit with the two separate models. Overall, there are some changes in the magnitude of the coefficients, but no changes in the signs of the regression coefficients or significance levels.
It is possible that respondents who did not give an answer about their vaccination preferences–for example, because they are still undecided–would decide to vaccinate or support mandatory vaccination after an adequate vaccination campaign. In a robustness check, we followed this argument by assigning respondents who refused to answer the question about voluntary or mandatory vaccination to the ‘yes’ category and repeated the logit estimation. This does not change our results (see S7.1 and S7.2 Tables in S7 File , S8 File provides our Stata code, which prepares the data and conducts all the statistical analyses, as well as the outputs of the multivariate estimations).
Finally, Table 6 provides a statistical comparison of the marginal effects from the model on willingness to get vaccinated ( Table 4 ) and attitudes toward mandatory vaccinations ( Table 5 ). We find no significant differences in marginal effects between the two models except for two variables: tertiary education and eastern federal states. The marginal effect for tertiary education is significantly larger for the willingness to get vaccinated model while the opposite is true for eastern federal states.
https://doi.org/10.1371/journal.pone.0248372.t006
Politicians must make decisions which are based on incomplete information yet have far-reaching consequences for public health, personal freedom, and economic prosperity. It seems that many citizens are prepared to behave responsibly in the sense that they are prepared to endure a ‘little sting’ for the good of all: a vast majority of the German population (70 percent) state that they would get vaccinated as soon as a vaccine against COVID-19 was available. This means that under favorable conditions, a legal duty to get vaccinated to achieve herd immunity might not be necessary. It should, however, be noted that the question was asked in a stylized context: Potential side effects or ineffectiveness of the then hypothetical vaccine were assumed away. Though there is no reason to believe the vaccines currently being administered are more problematic in this respect than any other vaccines in use, neither can strictly be guaranteed in reality. In addition, the time required for a vaccination, the process of the vaccination itself (i.e. the injection), bureaucratic administration (e.g. making an appointment with the family doctor) or any necessary co-payment should de facto reduce the willingness to get vaccinated. Furthermore, at the time of writing, not only is it still unclear how quickly a vaccine can even be produced in the quantity required and administered to enough people, it is also unclear how long its effect will last. It is not even clear what percentage of the population would have to be vaccinated to achieve herd immunity, as this also depends on individual behavior and legal (or ethical) norms which are likely to continue to change (e.g. an explicit or implicit obligation to wear a mask of a specific variety in public transport or a testing obligation for people returning from trips abroad) [ 31 , 32 ]. Hence, a sufficiently high willingness to get vaccinated in the ‘best case’ scenario investigated here is an idealization and in any case only one relevant factor among many.
We observed there to be gender differences in the willingness to get vaccinated: women are less willing to get vaccinated, and also less willing to support a policy of mandatory vaccination. This is surprising, given that men are generally less likely to engage in preventive behavior [ 33 ] and women have been shown to be more willing to engage in preventive behavior in the pandemic, for instance by wearing face masks when recommended [ 34 ], and they also seem to be more compliant with other measures in general [ 35 ]. However, men are also more severely affected by the coronavirus [ 36 ] and women generally more skeptical about vaccinations, especially against COVID-19 [ 37 ]. We don’t know whether our interviewees frame their decision to get vaccinated or not as a situation of a social dilemma, but if so, previous results on gender differences in cooperation suggest men and women might have to be addressed differently to influence their decisions [ 38 , 39 ]. We also observed that income and education increase the willingness to get vaccinated voluntarily. It has also been shown recently that the willingness to pay for a vaccine against Covid-19 is positively impacted by, among other variables, income [ 40 ].
A mandatory vaccination would almost certainly achieve herd immunity against COVID-19, since all those for whom there is no medical contraindication would also get vaccinated. About half of the respondents approve and disapprove, respectively, of such a mandatory vaccination policy. In this context, the strong disagreement among the participants of the study regarding the dangerousness of the virus is particularly striking. Many of those who reject a policy of mandatory vaccination assume the dangerousness of the virus is being overestimated by others, while those who approve of a policy of mandatory vaccination seem to believe the exact opposite. This is highly problematic: at most one of the two groups can be right. Plausibly, the interviewees themselves differ in how dangerous they think the virus is. This yields a concrete and important policy recommendation (see also [ 40 , 41 ]): we need more reliable data on the dangerousness of SARS-CoV-2 and to communicate this data more clearly to the general public. Though the ‘knowledge-deficit’ explanation of low vaccine uptake might not work for well-established vaccines [ 42 ], we have found evidence that this might be different for COVID-19.
We are not recommending a policy of mandatory vaccination in this paper, but merely investigating the attitudes of people towards it. A policy of mandatory vaccination would be an extreme solution to solve the potential problem of low vaccine uptake, and a lot may be said in favor of less extreme policies (as outlined in [ 15 ], for instance). Vaccination could also be made mandatory only for certain groups of people (e.g. nurses, physicians, physiotherapists, people working in confined spaces, people travelling on public transport etc.), or only after time has conclusively shown that not enough people actually get vaccinated. It might also turn out that people are unwilling to take the second dose of a two-dose vaccine, or not accept refresher doses, which would further complicate the situation and might require subtle intertemporal strategy choice. Before making any vaccination mandatory, people could also be paid or incentivized in other ways to accept it [ 43 ]. If, as we hope, people take the external effects of their action into account, and a sufficiently high number of people get vaccinated as a result, mandatory vaccination won’t be necessary.
This article investigates the willingness to get vaccinated and the acceptance of a policy of mandatory vaccination against COVID-19 in June and July 2020 in Germany. Our first main result is that a large majority of about 70 percent of adults in Germany would voluntarily get vaccinated against the novel coronavirus if a vaccine without side effects was available. Our second result is that about half of this population is in favor of, and half against, a policy of mandatory vaccination. Our third main result is that the individual willingness to get vaccinated and acceptance of a policy of mandatory vaccination correlates systematically with several socio-demographics (gender, age, education, income) but, overall, not with psychological characteristics of the respondents.
When interpreting the results from our survey, it should be noted that preferences were elicited in an ideal-typical situation: a vaccine which is effective and free of side effects is immediately available for the entire population at zero cost. Future research will have to show how actual vaccination behavior differs in real-life situations that deviate from this ideal-typical situation.
Supporting information
S1 file. variable definitions..
https://doi.org/10.1371/journal.pone.0248372.s001
S2 File. Comparison with further studies in Germany.
https://doi.org/10.1371/journal.pone.0248372.s002
S3 File. Complementary estimation results.
https://doi.org/10.1371/journal.pone.0248372.s003
S4 File. Additional diagnostics for the logit models.
https://doi.org/10.1371/journal.pone.0248372.s004
S5 File. Multicollinearity across explanatory variables.
https://doi.org/10.1371/journal.pone.0248372.s005
S6 File. Functional form assumptions and simultaneity.
https://doi.org/10.1371/journal.pone.0248372.s006
S7 File. Imputation.
https://doi.org/10.1371/journal.pone.0248372.s007
S8 File. Stata code.
https://doi.org/10.1371/journal.pone.0248372.s008
Acknowledgments
We thank Thomas Rieger for his outstanding research assistance.
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What is a vaccine.
A vaccine is a suspension of weakened, killed, or fragmented microorganisms or toxins or other biological preparation, such as those consisting of antibodies , lymphocytes , or mRNA , that is administered primarily to prevent disease.
A vaccine is made by first generating the antigen that will induce a desired immune response. The antigen can take various forms, such as an inactivated virus or bacterium, an isolated subunit of the infectious agent, or a recombinant protein made from the agent. The antigen is then isolated and purified, and substances are added to it to enhance activity and ensure stable shelf life. The final vaccine is manufactured in large quantities and packaged for widespread distribution. Learn more about mRNA vaccine creation.
What is a vaccine delivery system?
A vaccine delivery system is the means by which the immune-stimulating agent constituting the vaccine is packaged and administered into the human body to ensure that the vaccine reaches the desired tissue. Examples of vaccine delivery systems include liposomes , emulsions , and microparticles.
How do vaccines work?
A vaccine imitates infection so as to encourage the body to produce antibodies against infectious agents. When a vaccinated person later encounters the same infectious agent, their immune system recognizes it and can fight it off. Learn more.
Read a brief summary of this topic
vaccine , suspension of weakened, killed, or fragmented microorganisms or toxins or other biological preparation, such as those consisting of antibodies , lymphocytes , or messenger RNA (mRNA), that is administered primarily to prevent disease .

A vaccine can confer active immunity against a specific harmful agent by stimulating the immune system to attack the agent. Once stimulated by a vaccine, the antibody-producing cells, called B cells (or B lymphocytes ), remain sensitized and ready to respond to the agent should it ever gain entry to the body. A vaccine may also confer passive immunity by providing antibodies or lymphocytes already made by an animal or human donor. Vaccines are usually administered by injection (parenteral administration), but some are given orally or even nasally (in the case of flu vaccine). Vaccines applied to mucosal surfaces, such as those lining the gut or nasal passages, seem to stimulate a greater antibody response and may be the most effective route of administration. (For further information, see immunization .)

The first vaccine was introduced by British physician Edward Jenner , who in 1796 used the cowpox virus (vaccinia) to confer protection against smallpox , a related virus, in humans. Prior to that use, however, the principle of vaccination was applied by Asian physicians who gave children dried crusts from the lesions of people suffering from smallpox to protect against the disease. While some developed immunity, others developed the disease. Jenner’s contribution was to use a substance similar to, but safer than, smallpox to confer immunity. He thus exploited the relatively rare situation in which immunity to one virus confers protection against another viral disease . In 1881 French microbiologist Louis Pasteur demonstrated immunization against anthrax by injecting sheep with a preparation containing attenuated forms of the bacillus that causes the disease. Four years later he developed a protective suspension against rabies .

After Pasteur’s time, a widespread and intensive search for new vaccines was conducted, and vaccines against both bacteria and viruses were produced, as well as vaccines against venoms and other toxins. Through vaccination, smallpox was eradicated worldwide by 1980, and polio cases declined by 99 percent. Other examples of diseases for which vaccines have been developed include mumps , measles , typhoid fever , cholera , plague , tuberculosis , tularemia , pneumococcal infection, tetanus , influenza , yellow fever , hepatitis A, hepatitis B , some types of encephalitis , and typhus —although some of those vaccines are less than 100 percent effective or are used only in populations at high risk. Vaccines against viruses provide especially important immune protection, since, unlike bacterial infections, viral infections do not respond to antibiotics .

The challenge in vaccine development consists in devising a vaccine strong enough to ward off infection without making the individual seriously ill. To that end, researchers have devised different types of vaccines. Weakened, or attenuated , vaccines consist of microorganisms that have lost the ability to cause serious illness but retain the ability to stimulate immunity. They may produce a mild or subclinical form of the disease. Attenuated vaccines include those for measles, mumps, polio (the Sabin vaccine ), rubella , and tuberculosis. Inactivated vaccines are those that contain organisms that have been killed or inactivated with heat or chemicals. Inactivated vaccines elicit an immune response, but the response often is less complete than with attenuated vaccines. Because inactivated vaccines are not as effective at fighting infection as those made from attenuated microorganisms, greater quantities of inactivated vaccines are administered. Vaccines against rabies , polio (the Salk vaccine ), some forms of influenza , and cholera are made from inactivated microorganisms. Another type of vaccine is a subunit vaccine, which is made from proteins found on the surface of infectious agents. Vaccines for influenza and hepatitis B are of that type. When toxins, the metabolic by-products of infectious organisms, are inactivated to form toxoids , they can be used to stimulate immunity against tetanus , diphtheria , and whooping cough (pertussis).

In the late 20th century, advances in laboratory techniques allowed approaches to vaccine development to be refined. Medical researchers could identify the genes of a pathogen (disease-causing microorganism) that encode the protein or proteins that stimulate the immune response to that organism. That allowed the immunity-stimulating proteins (called antigens ) to be mass-produced and used in vaccines. It also made it possible to alter pathogens genetically and produce weakened strains of viruses . In that way, harmful proteins from pathogens can be deleted or modified, thus providing a safer and more-effective method by which to manufacture attenuated vaccines.
Recombinant DNA technology has also proven useful in developing vaccines to viruses that cannot be grown successfully or that are inherently dangerous. Genetic material that codes for a desired antigen is inserted into the attenuated form of a large virus, such as the vaccinia virus, which carries the foreign genes “piggyback.” The altered virus is injected into an individual to stimulate antibody production to the foreign proteins and thus confer immunity. The approach potentially enables the vaccinia virus to function as a live vaccine against several diseases, once it has received genes derived from the relevant disease-causing microorganisms. A similar procedure can be followed using a modified bacterium, such as Salmonella typhimurium , as the carrier of a foreign gene.

Vaccines against human papillomavirus (HPV) are made from viruslike particles (VLPs), which are prepared via recombinant technology . The vaccines do not contain live HPV biological or genetic material and therefore are incapable of causing infection. Two types of HPV vaccines have been developed, including a bivalent HPV vaccine, made using VLPs of HPV types 16 and 18, and a tetravalent vaccine, made with VLPs of HPV types 6, 11, 16, and 18.
Another approach, called naked DNA therapy, involves injecting DNA that encodes a foreign protein into muscle cells. The cells produce the foreign antigen, which stimulates an immune response.
Vaccines based on RNA have been of particular interest as a means of preventing diseases such as influenza , cytomegalovirus infection, and rabies . Messenger RNA (mRNA) vaccines are advantageous because the way in which they are made allows them to be developed more quickly than vaccines made via other methods. In addition, their production can be standardized, enabling rapid scale-up for the manufacture of large quantities of vaccine. Novel mRNA vaccines are safe and effective; they do not contain live virus, nor does the RNA interact with human DNA.
Vaccine-preventable diseases in the United States , presented by year of vaccine development or licensure.

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Background Vaccination is one of the cost effective strategies reducing childhood morbidity and mortality. Further improvement of immunization coverage would halt about 1.5 million additional deaths globally. Understanding the level of immunization among children is vital to design appropriate interventions. Therefore, this study aimed to assess full immunization coverage and its determinants ...
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The COVID-19 pandemic has created a new reality where individuals are faced with a previously unknown disease and its effects, providing a unique opportunity to investigate vaccine attitudes during a period of heightened disease salience. The present research reports findings from a longitudinal study conducted during the COVID-19 health crisis ...
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vaccine, suspension of weakened, killed, or fragmented microorganisms or toxins or other biological preparation, such as those consisting of antibodies, lymphocytes, or messenger RNA (mRNA), that is administered primarily to prevent disease. A vaccine can confer active immunity against a specific harmful agent by stimulating the immune system to attack the agent. Once stimulated by a vaccine ...