A Strong Case for Covid Vaccine Hesitancy

Why clinical trials cannot be safely shortened

The human immune system operates over long time scales. This is essential so that it can remember pathogens encountered during childhood for a lifetime, while also continually adapting to new microbes – both good and bad – and accurately distinguishing between human cells and invaders.

We like to think of an immune response as a simple process. Get exposed, develop antibodies, become immune. Such is the basis for both vaccination and natural immunity. In reality, however, the process is much more complex. I came to understand this personally ten years ago when as a new beekeeper I developed an allergy to bee stings.

Bee venom is irritating but not especially toxic to humans; in the absence of an immune dysfunction people can survive several hundred simultaneous stings without lasting harm aside from pain and swelling. Furthermore, no one will have an allergic reaction upon their first exposure to bee venom. However, following a bee sting or a series of stings, some people will begin to develop antibodies that trigger immune overreaction, which come to dominate over the more typical antibodies that tell the body this is nothing to worry about. It turns out that getting stung weekly or monthly favors the development of helpful antibodies (leading to minimal swelling over time), while getting stung once or infrequently can occasionally lead to the development of harmful antibodies, as happened in my case.

My reaction, while covering my body in hives, was thankfully not life-threatening, and an allergist prescribed a series of frequent injections of ever-increasing amounts of bee venom, in order to rebalance the levels of helpful and harmful antibodies. This proved successful, and since that time I have received hundreds of stings with no ill effect. For those interested in the immunological details of bee allergy, this link is very helpful: https://wncbees.org/wp-content/uploads/2014/08/Bee-Stings-Immunology-Allergy-and-Treatment-Marterre.pdf

I bring this up because allergies are an example of a broader phenomenon known as Antibody-Dependent Enhancement (ADE): in which the presence of antibodies against a particular agent leads to worse, rather than improved, outcomes.

Antibody-Dependent Enhancement is a known risk during vaccine development, and it tends to occur with particular viruses. In human vaccine trials it has been encountered with measles, dengue fever, and respiratory syncytial virus (RSV). If you Google “antibody-dependent enhancement vaccines”, this page is the first result, and it provides both a helpful summary of the issue and synopsis of relevant sources.

I recommend opening that page in another tab as you read this, as I will be referencing it below. While the cited information is accurate, the logic as applied to Covid-19 vaccination is dangerously flawed, and the basis for that failure is the importance of time.

The article discusses past instances of ADE occurring during vaccine trials – or soon after more widespread vaccine use – for measles, RSV, and dengue vaccines. Here are some relevant quotes, with emphasis added:

“Regarding safety, children vaccinated between 2 to 5 years of age in Asia were shown to have an increased risk of hospitalization secondary to dengue three years after the first vaccine dose compared with children who received placebo.” (link)

“In this case series, the authors describe seven patients aged 12 to 19 years who developed atypical measles 10 to 13 years after receipt of formalin-inactivated measles vaccine (FIMV).” (link)

“In this follow-up case series, the authors described 10 children who were hospitalized at the ages of 6 to 8 years with an atypical severe presentation of measles, five to six years after receipt of FIMV.” (link)

Antibody-dependent Enhancement can be quite severe. In one trial of a RSV vaccine, the hospitalization rate for this usually-mild childhood illness rose from 5% to 80% in vaccinated patients, with two deaths reported. (link)

With regard to the Covid-19 vaccines, the article offers the following assurance: “Neither COVID-19 disease nor the new COVID-19 vaccines have shown evidence of causing ADE. People infected with SARS-CoV-2, the virus that causes COVID-19, have not been likely to develop ADE upon repeat exposure. This is true of other coronaviruses as well. Likewise, studies of vaccines in the laboratory with animals or in the clinical trials in people have not found evidence of ADE.”

Moving on to the citations, we see the following statements, with emphasis again added (note that “Th2 response” essentially refers to antibody-dependent enhancement here):

“To determine whether mRNA-1273 (Moderna) vaccine induced Th2 responses, researchers immunized macaques with two doses of either 10 mcg or 100 mcg of mRNA vaccine at four-week intervals and challenged the animals eight weeks later with SARS-CoV-2.” (link)

Seven days after the second dose, a robust Th1 response was observed, but only a minute Th2 response, consistent with the unlikely occurrence of vaccine-associated enhanced respiratory disease, which is associated with Th2 responses.” (link)

After vaccination, macaques were challenged with SARS-CoV-2 without observable antibody-dependent enhancement of infection or immunopathological exacerbation.” (link)

What is clear to me, in reading this, is that the authors are confident that ADE is not a problem with the Covid-19 vaccines based on studies lasting at most a couple of months, while actual problematic ADE in past vaccination efforts only became apparent after a much longer observation period of multiple months up to 10+ years. Given the potential severity of ADE, I consider this to be a dangerous failure of scientific and precautionary thinking.

Adding to the concern here is the fact that vaccine animal trials for the closest-known relative of SARS-CoV-2, the original SARS(-CoV-1) virus, often encountered ADE. As noted in an analysis paper published in early 2021:
“Antibodies to the SARS-CoV-1 spike protein can mediate viral entry via Fc receptor-expressing cells in a dose-dependent manner (54). Jaume et al. (34) point out the potential pitfalls associated with immunizations against SARS-CoV-1 Spike protein due to Fc mediate infection of immune cells. This leads to the prediction that new attempts to create either SARS-CoV-1 vaccines, MERS-CoV vaccines (81), or SARS-CoV-2 vaccines have potentially higher risks for inducing ADE in humans facilitated by antibody infection of phagocytic immune cells. This potential ADE risk is independent of the vaccine technology (82) or targeting strategy selected due to predicted phagocytic immune cell infections upon antibody uptake.” (link)

It is true that, when animal trials of SARS-CoV-1 vaccines encountered ADE, this usually occurred the first time the vaccinated animals were infected with the virus. It is also true that this sort of immediate-term ADE has now been ruled out for the emergency-approved Covid-19 vaccines. However, we know that ADE *can* be a problem with SARS-family coronaviruses, and also that ADE can take months to years to appear and can be triggered by encountering new variants of the virus, or by waning immunity (i.e. higher antibody levels can be protective while lower levels can lead to enhanced disease).


There is a reason why vaccine trials typically last 5-10+ years, and there is no way to shorten this time period without significantly reducing confidence in long-term safety and effectiveness. This is doubly true when working with novel viruses, with viruses known to exhibit ADE, and with novel vaccine technologies. A rushed vaccine for a new pandemic strain of influenza, modeled after current flu vaccines, would carry a much lower level of risk and uncertainty than the current crop of Covid-19 vaccines.

This is all to say that I offer no personal apology to those who loudly insist that everyone must be vaccinated and those who refuse are selfish, ignorant, misanthropic, or misinformed. I see a very real risk that these vaccines could ultimately enhance the severity of Covid-19 through ADE such that we are no longer dealing with a virus that kills one out of 300 people infected but maybe one out of 100, or one out of ten. I understand the risk-benefit analysis for elders and vulnerable groups, but I cannot understand the push to vaccinate younger adults and *especially* children, given that these groups nearly all make a full recovery.

Furthermore, the vaccines are “leaky” – with vaccinated people still becoming infected and transmitting the virus, which negates the possibility of driving the virus to extinction through vaccination – and vaccine-mediated immunity also appears to wane rapidly, with people in Israel who were vaccinated back in January and February now catching Covid-19 at much higher rates than those vaccinated more recently.

I intend to stand strong against the social pressure to take these vaccines, which has long since deviated from the realm of science and is taking on concerning psychosocial dimensions. For others who are feeling this pressure and perhaps drawing concerning parallels to historical pogroms or childhood bullying, I highly recommend this perspective by Charles Eisenstein.

I am not anti-vaccine, and I hold no judgments against those who choose to be vaccinated. I may, in time, choose to receive one of the vaccines myself, if a sufficiently long time passes without evidence of ADE or immunity loss, or possibly if a viral mutation arises that is not just more infectious but also carries a much-elevated risk of disability and death. In this moment, though, I wish to convey that there remains more uncertainty (and potentially life-altering uncertainty at that) than most are willing to admit, and I find it deeply unethical that these vaccines are being promoted through coercion (“no jab, no job”) and shallow incentives like ice cream cones and lottery tickets rather than through carefully crafted, reasoned arguments. I think there is a good reason why PhDs are the most hesistant group in terms of Covid-19 vaccine acceptance, and the least likely to change our minds over the short term.

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2 Responses to A Strong Case for Covid Vaccine Hesitancy

  1. Matt Holbert says:

    Mark-

    Re: the PhD hesitancy…

    Did you catch the last line in the article on the survey? “I remain concerned about reaching the most hesitant subgroup of Americans,” said Mejia. “The only way to end this pandemic for real is to get enough people vaccinated that we can reduce the speed of new variants spreading.” It would be fun to see GVB and Robert Malone respond.

    On what authority does a ” Ph.D., M.P.H., special faculty at the CMU Dietrich College of Humanities and Social Sciences” have to opine on the vaccinations? I guess it’s because she’s “special.”

    • Mark says:

      Any claim that vaccination reduces the speed of variant spreading is rapidly being disproved by reality. For now it does still seem to provide some protection against severe illness, but I’m far from convinced that will continue to be the case in the months ahead.

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