Recently a number of people have reached out to me to ask how they can be vaccine advocates and how to deal with anti-vaxxers on social media. Here is my summary for the former:

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Here are some resources to help you:

Deplatform Disease’s Rules for Engaging Anti-Vaxxers on Social Media*

  • Your very first task is to recognize whether you are dealing with an anti-vaxxer. Right now, many people who aren’t very familiar with medicine or pharmaceuticals are being asked to suddenly take a pharmaceutical that may seem hastily developed. That is an understandable source of anxiety. It should not be stigmatized. These people need support and guidance to understand why it is safe and it is worth taking the time to explain it to them whenever possible and they are NOT anti-vaxxers. …

The question of how many doses are needed actually turns out not to be such a simple one. Both the Pfizer/BioNTech and Moderna are shown to be efficacious after two doses. So right now, regardless of what anyone says, everyone needs two doses of the vaccine, until such time as a single dose proves to provide highly efficacious (good at preventing disease) and durable (long-lasting) immunity. I fully support that study being performed, and I think Professors Tufekci and Mina make a good case for it here (though admittedly I am unsure that the NYT Opinions was the best place for the proposal, as some have pointed out). …

The Short Version: Anaphylaxis is a rapid-onset, rare manifestation of allergy which is life-threatening and involves two or more organ systems, usually including the skin and respiratory system (but not necessarily). The exact prevalence of anaphylaxis is not known but does appear to be rising (because the prevalence of allergy has been rising, for which many hypotheses have been proposed). Anaphylaxis has been documented in response to basically anything you can think of- exercise, cold air or water, heat, sunlight/ UV radiation, venom (it’s actually thought that this is how anaphylaxis evolved- animals which have anaphylactic reactions to venoms survive envenomation better), radiocontrast media (which is not the same as iodine allergy- no one is allergic to iodine), ethanol (the alcohol we drink), medications, and of course food. Even though all anaphylaxis is a medical emergency, the case-fatality ratio from anaphylaxis (despite frequent incorrect treatment) has been measured to be less than 0.001%. Anaphylaxis is foremost treated with epinephrine (though it is not unusual for people to require more than one dose from an Epipen)- despite common misconception it is NOT treated with antihistamines (though these can be given for comfort). The incidence of anaphylaxis from vaccines (excluding COVID-19 vaccines) has been measured before to be 1.31 per million vaccine doses (and in the 33 cases from that study which looked at over 25 million vaccine doses, none were fatal)- and thus is exceedingly rare. With COVID-19 vaccines, 8 cases of severe allergic reactions have been documented with just over 1 million doses doses- which makes for an incidence of approximately one per 125,000 doses of vaccine, which is still quite rare. It is not currently known what component of the vaccines is responsible, but current suspicions point to a component of the lipid nanoparticle that the mRNA is placed inside called PEG-2000. PEGs are very common additives in cosmetics, drugs, and foods, and thus allergy to them is generally very rare. Anyone receiving a vaccine is asked to stay for observation for 15 minutes in the event of a reaction, and in those who have a history of severe allergic reactions the Advisory Committee on Immunization Practices recommends observation for 30 minutes. …

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The short version: A preprint has emerged claiming that there is evidence that SARS-CoV-2 is reverse transcribed and integrated into the human genome. None of the evidence it provides justifies such a conclusion, and it demonstrates a failure to understand fundamental aspects of coronavirus biology and frankly the limitations of the methods used to make that conclusion. Furthermore there even appears to be an attempt by the preprint authors to make their data more difficult to scrutinize because it is available only upon request and not included in the paper. …

I had previously erroneously stated that the Moderna and Pfizer vaccines contained mRNA encoding only the spike receptor-binding domain; this was an error on my part. With so many vaccine candidates, including those that did use only the receptor-binding domain, I must have gotten confused. Both of these vaccines encode a pre-fusion stabilized (with a double proline substitution) full-length spike protein. I have gone through and corrected all erroneous references on the blog and regret this error. I will strive to be more diligent so as to not make such careless mistakes in the future.

The short version: Moderna’s phase 3 clinical trial data are available. They show that the vaccine has excellent efficacy at preventing COVID-19, and in particular, preventing severe COVID-19. Serious adverse events were rare in the trial, and in general, are probably not related to the vaccine (but safety monitoring should and will continue). The vaccine itself is very similar to the one made by Pfizer/BioNTech, but is much easier to store because it’s stable at higher temperatures. In general though, this vaccine provokes a strong immune response which can be uncomfortable (patients often experienced pain at the injection site, headache, fatigue, and joint pains; some nausea was also reported and some people did develop temporary swelling of their lymph nodes aka “glands” in their armpits), especially after the second dose, so if possible, I would aim to get it, especially the second dose, right before a period you can rest e.g. …

The Short Version: It is normal to feel crummy shortly after getting a vaccine. Vaccines provoke immune responses, which are uncomfortable and can trigger a number of behavioral changes in us e.g. we want to sleep more, we tend to become socially withdrawn, and we tend to become tired and eat less. There’s a lot that can be done to manage the discomfort after a vaccination, but you should avoid taking anti-inflammatory medications (e.g. acetaminophen and NSAIDs) before and during vaccination (but they are fine to take after).

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Reactogenicity: The Concept

The short version: Pfizer’s vaccine is currently under review for emergency use authorization in the US (and was recently given the green light from VRBPAC, meaning the FDA will likely approve its EUA shortly), and has been given limited regulatory approval in the UK and Canada. A review of the pre-licensure data paints the portrait of a very effective vaccine that is likely to cause short-lived but undeniably unpleasant side effects, particularly after the second dose. No significant safety concerns were noted. There were also reports that two healthcare workers in the UK who had epinephrine autoinjectors received the vaccine and suffered anaphylactoid reactions. They are recovering well. The UK subsequently declared that anyone with a history of severe allergy avoid this vaccine, which is precautionary and does not make very much sense scientifically. The likely culprit in my view is PEG, a component of the lipid nanoparticle. It is expected that as the vaccine rolls out and more people receive it some adverse reactions will occur. However, this does not mean that YOU will have a reaction or are likely to have one, and in isolation, this does not mean the vaccine is unsafe. …

I’ve gotten this question from a few people, and I initially put out a detailed post explaining what the current guidances are from ACIP, IDSA, and the Immune Deficiency Foundation but I decided that regardless of how many disclaimers I put, it was too close to medical advice and it was probably too technical for most people wondering about it to benefit from it.

In general, when an individual has altered immunocompetence (which is to say, their immune system cannot effectively respond to antigens either because of HIV infection, genetic causes, certain drugs, surgical removal of the spleen, etc.) there are some important differences in how they need to be vaccinated. Principally, the big concern is live attenuated vaccines. Live attenuated vaccines contain a real, replicating pathogen that has been adapted to grow poorly in humans. Examples include MMR, and the BCG vaccine for tuberculosis (not routinely given in the US). In an immunologically competent person, these are no problem. But because people with altered immunocompetence can have trouble clearing pathogens, in some cases live attenuated vaccines can be dangerous and reproduce the disease they are intended to prevent. For some of these individuals live bacterial vaccines may be okay but live viral ones may not or vice versa. …

The short version: Antibody-dependent enhancement (ADE) is a rare phenomenon basically limited to dengue and a few other infections where the presence of antibodies makes a disease worse. The antibodies can come from anywhere: prior infection, passive immunization (e.g. convalescent plasma), or vaccines. This was a concern for the development of COVID-19 vaccines. The current evidence we have at this point in almost a year of a pandemic is that this concern is not reasonable. Convalescent plasma has been used extensively throughout this pandemic and if ADE were significant, we would have evidence by now.

Part I: The Fundamentals

A few times on my blog, I’ve discussed antibody-dependent enhancement (ADE) but I’m seeing it come up more and more as we approach EUA and eventually approval for COVID-19 vaccines, so I thought it would be helpful for people to have a separate post discussing it in some depth. …


Edward Nirenberg

I write about vaccines here. You can find me on Twitter @enirenberg and at (where I publish the same content without a paywall)

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