The real problem with the Johnson and Johnson and AstraZeneca vaccines.

I label this post as my opinion, and I’m sure many scientists and physicians in other fields would argue with it.

However, now that the Johnson and Johnson adenovirus based COVID-19 vaccine has been approved again for use in the U.S., I think it’s important to provide perspective to individuals who are considering taking this vaccine. My comments also pertain to any of the adenovirus based COVID-19 vaccines, including the AstraZeneca and the Russian vaccines.  

As reported in Wikipedia, Adenoviruses (members of the family Adenoviridae) are complex viruses. The name of the virus derives from their initial isolation from human adenoids in 1953.[2] They contain at least 38 proteins.

Adenovirus Structure

There are more than 50 distinct human adenoviruses (serotypes) that cause a wide range of human illnesses, from mild respiratory infections in young children (the common cold) to life-threatening multi-organ disease in people with a weakened immune system.[1]

These viruses have a 20-sided capsule (covering) strongly protecting their genetic material (nucleocapsid). The genetic material itself is double stranded DNA genome, which is very stable and similar in structure to human genes. In addition, because these viruses have no outside lipid covering, they are not easily degraded by heat or detergent. Adenoviruses are the largest known non-enveloped viruses.

The stability of adenoviruses is a large part of the attraction to using them as the basis for vaccines, since storage and refrigeration are less onerous. Also, methods of genetically modifying and manufacturing adenovirus are well developed.

In contrast, SARS-CoV-2, the virus causing COVID-19, is a slightly smaller virus with a lipid envelope and unstable, single-stranded RNA as its genetic material. While it has 29 proteins, only one, the spike protein, is necessary to induce protective immunity. In fact, the RNA vaccines (Pfizer-NBioTech, Moderna) produce only a fragment of the spike protein and result in highly effective immune protection.    

Why do I think it is a problem to use whole adenovirus to immunize against COVID-19? 

It is not because it will cause adenovirus illnesses. When used in vaccines, the adenoviruses are modified in a way that prevents them from reproducing in humans. Thus, while these viruses can still infect humans, in vaccines they do not cause infection related disease. 

My major concern is the need to inject 38 different adenovirus proteins and adenovirus double stranded DNA into an individual to induce immunity to a single fragment of an unrelated SARS-CoV-2 protein (that has been added to the adenovirus). The person being injected with this vaccine will make immune responses to all 38 adenovirus proteins along with the important fragment of the SARS-CoV-2 spike protein.

The 38 adenovirus proteins you get as an “extra” in adenovirus based COVID-19 vaccines!

Because adenovirus infections are so common, almost every person has already been infected with adenovirus by the age of 18. Therefore when an individual receives an adenovirus based vaccine it is a booster response to the 38 adenovirus proteins. This results in intense immunity to the adenovirus proteins, often even stronger than the immunity generated to the coronavirus spike protein included in the virus!   

The Coronavirus spike protein. Only immunity to the very top portion (green) of the protein is needed to block infection.

Making an immune response to all of these different viral proteins could lead to an immune response to your own proteins (that look like the viral proteins). This could cause your immune system to attack itself resulting in autoimmune disease. This was only a theoretical concern until the blood clotting issues arose and appeared to be related to autoantibodies to platelet factor 4. This proved that this concern was real.

Why is this rare autoimmune disease only seen in young women? For reasons that are not entirely understood, young women are more prone to autoimmune disease, and this likely is related to hormones. Not surprising, this predilection decreases after menopause sparing older women. Also, the rarity of the autoimmune disease is likely because it only happens in individuals that have certain genes in their immune systems that cause them to develop these cross-reactive antibodies.

In any case, injecting a whole, unrelated virus with 38 proteins to induce immunity to a single fragment of SARS-CoV-2 spike protein does not seem an optimal vaccine approach, especially compared to the RNA vaccines which induce immunity only to the spike protein.

Regardless of this, we do need to have everyone vaccinated against COVID-19.

If you have no option but the Johnson and Johnson vaccine because you live in an area where you cannot obtain one of the RNA vaccines, then by all means get vaccinated with that vaccine. The risks are rare. However, if you have the option, and especially if you’re a woman of childbearing age, try to get one of the RNA vaccines.  

Published by jbakerjrblog

Immunologist, former Army MD, former head of allergy and clinical immunology at University of Michigan, vaccine developer and opinionated guy.

2 thoughts on “The real problem with the Johnson and Johnson and AstraZeneca vaccines.

  1. I’ve enjoyed reading your blog over the past year, and especially appreciate its balance. Others to whom I forward your posts often say the same. I’m curious to know your opinion about what is driving the recent (last 10 days or so) sharp reduction in positive cases in Michigan. I can speculate that it’s due to the pace of vaccinations combined with late-arriving social responsibility (after we partially reopened a couple of months ago), but the roller-coaster decrease seems to suggest something more?

    John Shea

    Liked by 1 person

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