Steven S. Cheng* and Bianca A. Lepe
Edited by Sumedha Sachar and Friederike M. C. Benning
Article | Aug. 30, 2021
*Email: scheng1@g.harvard.edu
DOI: 10.38105/spr.7ofzvhm6x9
Highlights
- Vaccines have significantly reduced infectious disease burden in society, saving numerous lives and improving people’s health.
- Aiming to increase vaccination rates among the population, some policymakers have considered instituting vaccine mandates.
- Vaccine mandates should be crafted carefully to ensure that exemptions are given when necessary, that they do not exacerbate societal inequities, and that they do not provoke societal backlash.
Article Summary
Vaccination is a public health measure that is routinely performed to reduce the risk of contracting a particular infectious disease. Taking advantage of the body’s immune system, vaccination can confer immunity against disease-causing pathogens. Though vaccination generally is not able to yield absolute immunity, the procedure has nonetheless improved public health and reduced infectious disease mortality globally, saving millions of lives each year [1]. If a high enough proportion of a population obtains immunity to a particular pathogen such that the spread of the associated disease has slowed and members of the population without immunity are also protected, then herd immunity has been achieved. Consequently, there have been a number of debates about using policymaking tools to achieve this high population vaccination rate, including policies of mandatory vaccination. Here, we discuss the scientific background of vaccination, present frameworks for understanding the arguments for and against mandatory vaccination policies, and highlight data and a case study in support of these arguments within the context of the United States. We hope to better inform the policymaking community of the factors that must be weighed when considering a mandatory vaccination policy.
Scientific background of vaccination
How do vaccines work?
Infectious diseases are caused by pathogens such as bacteria, viruses, fungi, and parasites that invade the human body. Typically, vaccines consist of live attenuated or dead pathogens, no longer able to cause disease, along with an adjuvant. The body’s immune system recognizes the former as a foreign substance and begins to mount an immune response directed against the pathogen through the production of proteins that protect cells called neutralizing antibodies. Adjuvants are substances used in vaccines to promote a robust immune response. By training the immune system to recognize and neutralize a particular pathogen, vaccination substantially decreases a person’s risk of becoming severely infected and/or ill upon exposure to that pathogen (Fig. 1) [2]. Recent advances in biotechnology have led to other types of effective and easy-to-produce vaccines, e.g., messenger RNA vaccines and purified antigen vaccines.

Figure 1: Schematic illustrating how live-attenuated/inactivated vaccines lead to immunity. In response to a vaccine, the body’s immune system produces antibodies against specific pathogens which neutralize them the next time a person is exposed to the same pathogen, preventing severe disease.
The efficacy of a vaccine is calculated from the difference between the number of infections in a vaccinated group and a control or placebo group (which is not given the vaccine) in a randomized clinical trial. Vaccine effectiveness is similarly calculated based on how well the vaccine performs in the general population. Different vaccines often have different efficacies depending on what disease they are aimed against, what delivery technology they use, and other patient-specific factors such as age [3]. For example, some vaccines are highly effective; the Centers for Disease Control and Prevention (CDC) reports that the polio vaccine is 99% to 100% effective with three doses and the measles, mumps, and rubella (MMR) vaccine is 97% effective with two doses [4, 5]. For measles, an estimated 23 million lives have been saved since 2000 due to vaccines and the World Health Organization (WHO) annual reporting illustrates the drop of measles cases corresponding to the rise of vaccine coverage (Fig. 2) [6]. Recently developed messenger RNA-based vaccines by Pfizer/BioNTech and Moderna achieved roughly 95% efficacy in protection against COVID-19 and have been able to protect many lives [7, 8]. On the other hand, the influenza vaccine is updated annually to account for changing influenza strains and has varying effectiveness. In years when the vaccine virus is matched with the circulating virus, the vaccine effectiveness is in the range of 40%–60%, while in years when there are vaccine mismatches, the effectiveness can be as low as 13% as seen in the 2014–2015 season [9].

Figure 2: Number of measles cases (millions) versus immunization coverage percentage, globally from years 1980–2019. Note that as immunization coverage increases, disease cases decrease. Adapted from WHO [12].

Figure 3: Illustration of how vaccination can lead to herd immunity and slow the spread of disease. (A) Spread of disease through a susceptible community. Everyone is exposed to disease and infected over time. (B) Spread of disease through a mostly vaccinated community. Immunity through vaccination prevents infections by blocking off paths for infection to spread.
Why are some people hesitant to be vaccinated? One major challenge in achieving high vaccination rates is countering disinformation and misinformation regarding vaccine safety. There have been numerous controversies regarding the safety of vaccines, most notably around a purported relationship between the MMR vaccine and autism, and the potential for vaccine-induced Guillain-Barré syndrome (GBS), a disease in which the body’s immune system mistakenly attacks the nervous system. Consequently, vaccine hesitancy is a major issue in many societies, including the U.S., making it essential to contextualize or debunk the supposed risks of vaccination. The report suggesting a link between the MMR vaccine and autism has been retracted due to ethical misconduct and financial conflicts of interest. The scientific inaccuracies and fraudulent research practices in this study have led to widespread rejection by the scientific community [13]. Also, numerous studies have since debunked this proposed association. Vaccine-induced GBS became a concern during the 1976 swine flu vaccination program in the U.S. as the vaccine appeared to increase the risk of developing GBS. This association has so far largely been limited to the 1976 swine flu vaccine. Moreover, influenza infection has been found to be a greater risk factor for GBS than influenza vaccination, making vaccination preferable over natural exposure [14]. Some religious groups also show hesitance towards certain vaccines for many reasons, which are not further elaborated on in this work [15]. Specifically in the case of COVID-19 vaccines, some vaccine hesitancy also arises from the novelty of the messenger RNA vaccines and the speed with which the vaccines were developed [16]. Numerous studies, however, have demonstrated that the vaccines are safe and effective [7, 8].
Vaccines are not innocuous; they often lead to side effects such as fever, fatigue, muscle pain, joint pain, and headache. However, these side effects are validation that the vaccine is eliciting an immune response, and they are minor relative to the risks of infection with the active pathogen. Conducting randomized clinical trials and presenting safety and efficacy results in a clear, transparent manner is key to building public faith in vaccination programs. It should be noted that this is not sufficient; effective communication and other strategies discussed later must complement transparent vaccine development to encourage vaccine uptake. There are cases in which vaccination may pose certain health risks, such as with immunocompromised patients, whose immune systems have impaired function. In these cases, caution must be taken to fully understand the risks in order to prevent undesirable events, for example, infection by a live attenuated vaccine. While vaccines are not entirely without side effects, the medical and scientific communities should emphasize that minor side effects are common in the general population and the benefits of vaccination greatly outweigh the risks [17].
There are numerous other factors that can impede vaccination campaigns including distribution to isolated communities, availability of medical staff, vaccine storage, and vaccine supply. As has been seen with COVID-19, these factors are especially important in the midst of an active pandemic when vaccine demand often exceeds vaccine supply [18]. Successful vaccination efforts depend on resolving each of these factors in addition to encouraging vaccine uptake.
Ethical & legal frameworks for analyzing mandatory
vaccination
As vaccinating a large enough proportion of the population to achieve herd immunity may encounter a number of potential roadblocks, some policymakers have proposed mandatory vaccination to accelerate the road to herd immunity. Before outlining data and case studies regarding vaccination policy, we discuss the ethical and legal frameworks for understanding the arguments around mandatory vaccination.
Is mandatory vaccination ethical? In a utilitarian analysis, the most beneficial policy option is one that maximizes societal benefits while minimizing societal costs [19]. Under this framework, some argue that vaccine mandates should be used to increase vaccination rates, as the lives saved and the public health benefits outweigh the loss of freedom for people to make independent decisions about vaccination [20]. In a contrary argument, some biomedical ethicists emphasize the importance of patient autonomy – patients should be able to make their own choices about whether or not to receive a particular healthcare intervention [19]. By definition, a vaccine mandate would infringe upon patient autonomy by financially or legally penalizing those who choose not to receive a vaccine, thus violating the clinician-patient relationship [21].
Is mandatory vaccination legal? In the U.S., vaccine mandates have long existed in various forms. At the beginning of the 20th century, the Commonwealth of Massachusetts allowed “the board of health of a city or town if, in its opinion, it is necessary for the public health or safety shall require and enforce the vaccination and revaccination of all the inhabitants thereof and shall provide them with the means of free vaccination” (1). Healthy adults refusing the vaccination would be fined. Henning Jacobson, who was fined under this policy, argued that this was a violation of the Fourteenth Amendment which states that “[n]o state shall make or enforce any law which shall abridge the privileges or immunities of citizens of the United States; nor shall any state deprive any person of life, liberty, or property, without due process of law; nor deny to any person within its jurisdiction the equal protection of the laws” (2). In Jacobson v. Massachusetts, the Supreme Court ruled that the vaccine mandate adopted by the City of Cambridge and authorized by the Commonwealth of Massachusetts was valid under the “police power of a State” to enact regulations that protect public health (3). This ruling was reaffirmed in Zucht v. King, in which the San Antonio school district was being sued for excluding unvaccinated students (4). Since then, school immunization mandates have existed across the U.S. and have been upheld numerous times in courts [22].
Presently, all fifty states have some form of vaccination requirement for enrolling in public schools. While all states offer medical exemptions to this requirement, there are differences in the non-medical exemptions (NMEs) offered. Specifically, 45 states and Washington D.C. grant religious exemptions to this requirement; 15 states also grant philosophical (personal, moral, or other) exemptions to this requirement (Fig. 4) [23]. Under the National Childhood Vaccine Injury Act, federal law requires that medical providers provide vaccine information statements prepared by the CDC to patients or their legal representative for a number of different vaccines (5). Parental consent for vaccination is generally required under state laws, though there are limited exceptions, such as for vaccination against sexually transmitted infections, through minor consent laws [24]. Some state legislatures have proposed bills allowing adolescents to consent to certain vaccines with the goal of achieving higher vaccination rates [24]. Policymakers considering vaccine mandates should keep these legal frameworks in mind when thinking about informed patient consent.

Figure 4: Map of non-medical exemptions from school immunization requirements by state in 2020. White states do not allow any non-medical exemptions; pink states allow only religious exemptions; and red states allow exemptions due to any personal belief. Adapted from [23].
Case study of widespread vaccination health
outcomes
Important considerations for devising mandatory
vaccination policies
Conclusions
Acknowledgements
The authors would like to thank the Science Policy Review leadership team and editorial staff, and the reviewers for their helpful feedback.
Citation
Cheng, S. S. & Lepe, B. A. The path to herd immunity: is mandatory vaccination the answer? MIT Science Policy Review 2, 82-89 (2021). https://doi.org/10.38105/spr.7ofzvhm6x9.

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Legislation Cited
(1) Enforcement of vaccination of inhabitants of towns, MGL c.111 § 181.
(2) U.S. Const. Amend. XIV, § 1.
(3) Jacobson v. Massachusetts, 197 U.S. 11, 25 S. Ct. 358, 49 L. Ed. 643 (1905).
(4) Zucht v. King, 260 U.S. 174, 43 S. Ct. 24, 67 L. Ed. 194 (1922).
(5) National Childhood Vaccine Injury Act, 42 U.S.C. §§300aa1-34 (1986).
(6) L.D. 798 (129th Legis. 2019).
(7) H.B. 1638, 362 (66th Legis. 2019).
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Steven S. Cheng
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA
Bianca A. Lepe
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA