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Why might the U.S.A. fail to reach herd immunity despite having effective vaccines?

We need sober, realistic responses to recent COVID-19 vaccine news.

Kyle Tretina, Ph.D.

With the announcement of early data indicating that vaccines from Moderna [1], as well as from Pfizer and BioNTech [2] are more effective than most experts predicted, is there reason to be cautiously optimistic? Both vaccines were selected for US Operation Warp Speed [3] and are expected to become the first vaccines licensed for human use, are well supported by previous scientific studies and comprehensive clinical trials [4] , and fall within a vaccine development landscape [5] that is well touted to be a promising source of an effective vaccine, so why could they fail?

Many may expect that the vaccine will provide long-lasting, sterilizing immunity to infection.

Failure is the result of unmet expectations, and there is reason to believe that experts have very high expectations for these COVID-19 vaccines [6–7]. In an era when we have common vaccines that provide decades of protection [8](e.g. Tetanus, Diphtheria, Rubella, Measles, etc.), the bar is set very high. Since the 18th century, vaccines have been used to eradicate the diseases of smallpox and rinderpest, nearly eradicated polio, and the end of measles is in sight. Many scientists think that vaccines are the best thing to happen to human global public health after clean water and sanitation [9]. However, even as our knowledge of immunity to some infections is far more insightful than at any point in the history of mankind, the gap between what we know about COVID-19 and what we think we know is unclear.

Some common vaccines protect against viral infection very effectively. There is a vaccine against Hepatitis A (Hep A), a viral liver disease, that can provide >90% protection against symptomatic disease as well as asymptomatic infections [10]. The vaccine against human papillomavirus (HPV) provides essentially 100% protection against infection [11]. This is called “sterilizing immunity”, which could decrease with age after a few decades, but can be maintained to some extent via the adaptive immune system [12].

However, the HPV vaccine is exceptional. Many vaccines are primarily intended to prevent disease and do not necessarily protect against infection or transmission nearly as efficiently. According to the CDC, influenza vaccine effectiveness (verified disease confirmed after a visit to the doctor or hospital) in the last fifteen flu seasons has ranged from 10% in the 2004–2005 season to 60% in the 2010–2011 season [13]. Flu vaccines are recommended on an annual basis because the duration and strength of immunity plummets on a yearly timescale [14]. In the case of an acellular pertussis vaccine, vaccinated individuals had a significantly shorter duration of chronic cough than controls [15,16]. Vaccination has also been shown to lessen disease for varicella and rotavirus infections [17,18].

There are many hopes [19], dreams and economic [20] futures riding on the discovery of an effective COVID-19 vaccine, and all of the data indicates that available vaccines live up to that hype, indicating that they are safe and induce highly efficient protection against SARS-CoV-2 infection for months. However, it’s not clear exactly how long that protection endures and whether booster shots will be needed. The data seem clear so far, but is sound scientific data enough for Americans?

The social acceptance rate of any COVID-19 vaccine may not be enough.

Worldwide, the uptake of vaccines has improved dramatically over the past few decades. Vaccines are perhaps the cheapest and most effective way to prevent infections, and most surveyed people think that vaccination is important [21] and that they would very likely take a COVID-19 vaccine should one become available to them [22], but that consensus might not be large enough in the United States [23–26].

While these vaccines have far surpassed the 50% efficacy standard set by the FDA for regulatory approval, is an >90% effective vaccine enough for sufficient public adoption? Surveys suggest that somewhere around 50–72% [27,28] of people in the U.S. would get a COVID-19 vaccine, should it become available, with physician advice playing the largest role in their decision [29]. In fact, most adults have expected a treatment or cure before the end of the year, and a vaccine in 2020 [28], or some time in 2021 [27]. This is approximately the same range of coverage that has been estimated to be required for herd immunity (55–82%) [30–31], meaning that small changes in public opinion (e.g. due to politicization [32]) about any potential vaccine could have important implications for how effective that vaccine is in practice.

It Ain’t What You Do It’s the Way That You Do It

There is often a gap between the insights of people who generate analysis and those who use them [33], and the insights of public health experts and the general public might be no different. Just like the vaccine itself, there are too many variables right now to predict whether the timing and delivery of the news about a potential vaccine is effectively inoculating the minds of Americans against the doubt and distrust [34] that is so prominent against the government and pharmaceutical companies [35]. Humans don’t make decisions well if they are given multiple choices [36], which is important when it might take multiple vaccines to get us back to near-normality. There are many technical hurdles that vaccine producers have yet to overcome with the scaling of new technologies (i.e. RNA-based designs [37]), and even newer vaccines could have further optimized designs (e.g. viral target, delivery route, timing, dose, etc.) [38] to provide the long-lasting protection needed for herd immunity and the eradication of COVID-19.

The current social climate and scientific data make the outcome of any vaccination campaign in the U.S. very difficult to predict.

With the pandemic months being often called “uncertain times” [35,39], Americans are discovering, to some extent, a peek into the life of a scientist. Variations in the timing of states reopening, kids returning to schools, enforcement of PPE requirements, and the vaccine rollouts are all experiments with uncertain outcomes. It’s important for us to now examine our biases and determine, before a vaccine become immediately available to us, who we trust and what kind of evidence would convince us to take the vaccine.

References

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Kyle Tretina, Ph.D.

Product Manager, Founding Team Member - Interdisciplinary thinking, genomics, infection, immunity, and science communication.