The claims that animal studies have shown significant pulmonary inflammation, …

Comment on Are mRNA Vaccines for COVID-19 helpful or harmful? by Sean Pitman.

The claims that animal studies have shown significant pulmonary inflammation, and other negative outcomes, following mRNA vaccination when these animals were then exposed to the live COVID-19 virus (not mentioned in the above-referenced interview with Wakefield) don’t seem to be true as far as I’ve been able to discover. Both of the mRNA vaccines (from Pfizer and Moderna) were simultaneously tested on animals while they were conducting Phase 1 trials on humans. The vaccines were tested on mice and macaques in particular. And, none of these tests showed any enhanced inflammation or reaction with subsequence COVID-19 exposure. Just the opposite is true. For example:

“Vaccination of nonhuman primates with mRNA-1273 induced robust SARS-CoV-2 neutralizing activity, rapid protection in the upper and lower airways, and no pathologic changes in the lung.” (Link).

“Mice vaccinated with these mRNAs were protected against lung infection when researchers later exposed the rodents to SARS-CoV-2, the coronavirus that causes COVID-19” (Link).

“The researchers injected ARCoV into the muscle tissue of 16 mice and provided a booster shot two weeks later. The vaccine elicited the production of high levels of neutralizing antibodies, which protect host cells by preventing the virus from interacting with them. These antibodies were cross-reactive, offering broad protection against three different strains of SARS-CoV-2. In addition, the vaccine increased the number of T cells in the spleen. Mice that received two doses of ARCoV and were exposed to SARS-CoV-2 35 days later showed no signs of viral RNA in the lungs or trachea and no lung damage or inflammation. Results from 20 cynomolgus monkeys showed that two ARCoV doses induced a virus-specific T cell response and the production of neutralizing antibodies at levels that far exceed those seen in most recovered COVID-19 patients. Moreover, none of the vaccinated animals experienced adverse effects.” (Link)

Also, human double-blinded trials in more than 70,000 people showed no such enhanced inflammation or reaction with COVID-19 exposure with prior mRNA vaccination.

University of Pennsylvania professor of medicine Dr. Drew Weissman, who has been studying mRNA and mRNA vaccines for decades, said they do not cause dangerous inflammation to animals. Along with the vaccines for Pfizer and Moderna both passing animal trials, they also passed clinical trials on humans where they were tested on more than 70,000 people (Link).

Perhaps, though, your wife is referring to a paper published by Timothy Cardozo and Ronald Veazey (October, 2020) cited concerns over what is known as “antibody-dependent enhancement” of vaccines? – with the potential to increase a negative response to the actual viral infection as compared to those who never had the vaccine? This concern is based on the observation of more severe disease occurring in individuals who received vaccines such as the one for dengue fever. In a 2018 study, scientists at La Jolla Institute for Immunology showed that newborn mouse pups harboring anti-Zika antibodies were more vulnerable to death from dengue exposure than mice that lacked anti-Zika antibodies. Certainly, this is an example of antibody-dependent enhancement (ADE). However, ADE has not been shown to occur in individuals that received COVID-19 vaccines during the double-blinded trials over many months or since the mRNA vaccines have started to be given to medical providers (like me).

Now, the reasons why ADE isn’t a significant concern for the mRNA vaccines against the COVID-19 virus is partly due to the fact that the COVID-19 virus does not infect macrophages in a way that is pro-inflammatory:

SARS-CoV infection of macrophages is abortive and does not alter the pro-inflammatory cytokine gene expression profile after antibody-dependent uptake4. Findings to date argue against macrophages as productive hosts of SARS-CoV-2 infection (Link).

For more specific details regarding the underlying science of immunology, see:

Vaccines that elicit neutralizing antibodies against the S protein reliably protect animals from SARS-CoV challenge without evidence of enhancement of infection or disease. These data suggest that human immunization strategies for SARS-CoV-2 that elicit high neutralizing antibody titres have a high chance of success with minimal risk of ADE. For example, subunit vaccines that can elicit S-specific neutralizing antibodies should present lower ADE risks (especially against S stabilized in the prefusion conformation, to reduce the presentation of non-neutralizing epitopes8). These modern immunogen design approaches should reduce potential immunopathology associated with non-neutralizing antibodies… It is encouraging that a recent assessment of an inactivated SARS-CoV-2 vaccine elicited strong neutralizing antibodies in mice, rats and rhesus macaques, and provided dose-dependent protection without evidence of enhanced pathology in rhesus macaques (Lee, et. al., 2020).

Some of the earlier attempts at a SARS vaccine showed ADE effects in mouse models, and further work showed that this seemed to be linked not so much to the antibody response as to the T cell response. Specifically, a “Th2” heavy response (as opposed to more Th1 or a balance between the two), was linked to lung pathology. Those are subdivisions of the CD4+ T cells, based on which cytokines they produce, and these results alerted everyone to keep an eye out for that. Mouse immunogenicity studies with the current vaccine candidates did not show these effects… This has been why we’ve seen so many vaccines taking care to put the Spike protein into its “prefusion” conformation. The worry has been that if antibodies are generated to it after it’s had a chance to bind to human cells, that gives you a better chance for nonneutralizing ones (and thus potentially a better chance for ADE). And you’ll have noticed the emphasis on neutralizing antibody titers along the way as well – that would have been there anyway, but a high proportion of outright neutralizing antibodies is also a safeguard against antibody-driven enhancement of disease. (Dr. Derek Lowe, December 18, 2020)

So, I fail to see any solid support for Wakefield’s claim here either. There is just no scientific evidence to support any of Wakefield’s main concerns or arguments against the mRNA vaccines – from either human or animal testing. To the contrary, these mRNA vaccines have proven themselves to be safer and more effective in humans than would have been originally predicted – in the face of extensive testing in tens of thousands of human subjects (soon to be millions – including me since I’ve already received the first Pfizer vaccine injection, with my second injection scheduled for this coming Friday).

Sure, I’m just a pathologist (with some fairly extensive training in genetics and the immune system via my subspecialty in hematopathology – which includes the study of the white blood cells that make up the immune system), but I know some vaccine experts and many on the front lines who are directly dealing with this pandemic face-to-face. The vast majority of those who are most familiar with COVID-19 and the mRNA vaccines, and their relative risks, strongly favor getting the vaccine – and have taken it themselves and would give it to their friends and family if they could at this point.

Sean Pitman Also Commented

Are mRNA Vaccines for COVID-19 helpful or harmful?

1. I assume some defective mRNA strands and lipid layers can be generated during the myriad of involved complex chemical processes. Do we understand percentage of defective nanoparticles / mRNA strands? Does process include QA that somehow reduces or eliminates potentially harmful defects. What is risk of defective mRNA strands that could encode for harmful proteins? Any other associated risks here that I am not addressing?

Given that the mRNA sequences in the Pfizer and Moderna vaccines are synthetically produced, I would say that there are very few defective mRNA sequences. And, when it comes to producing proteins based on these few defective sequences, the additional risk from such defective sequences for the human body would be, effectively, zero. In fact, a few slight variations in the protein sequence for the spike protein would only result in slight variations in the immune system response. And, producing such slight variations are already part of how our human immune system is programmed to work – automatically producing slight variations in the antibodies produced against a particular type of foreign antigen, for example.

2. How much independent review occurred with these vaccines? Is the Global Advisory Committee on Vaccine Safety the only body that reviewed. Do scientiests get hands-on and eyes-on access to the actual chemical processes to verify what is happening (in vitro and in vivo), or are they just provided with white papers and reports for review?

A great many scientists were involved in the production and review of the mRNA vaccines. These vaccines, how they work, and their effects on human biochemistry are very well known by a great many scientists who work in this field of immunochemistry. There are no fundamental secrets here.

3. Some papers and FAQs claim the generated viral “spike protein” is presented on the cell surface. Some of your dialogue here seems to indicate that this is not the case. Which is it? How is it presented? Is it presented in a variety of ways?

Here are a few diagrams that illustrate what’s happening within different cells of the body where the mRNA sequences are decoded and presented:

Mechanism of action of mRNA vaccines. 1. The mRNA is in vitro transcribed (IVT) from a DNA template in a cell-free system. 2. IVT mRNA is subsequently transfected into dendritic cells (DCs) via (3) endocytosis. 4. Entrapped mRNA undergoes endosomal escape and is released into the cytosol. 5. Using the translational machinery of host cells (ribosomes), the mRNA is translated into antigenic proteins. The translated antigenic protein undergoes post-translational modification and can act in the cell where it is generated. 6. Alternatively, the protein is secreted from the host cell. 7. Antigen protein is degraded by the proteasome in the cytoplasm. The generated antigenic peptide epitopes are transported into the endoplasmic reticulum and loaded onto major histocompatibility complex (MHC) class I molecules (MHC I). 8. The loaded MHC I-peptide epitope complexes are presented on the surface of cells, eventually leading to the induction of antigen-specific CD8 + T cell responses after T-cell receptor recognition and appropriate co-stimulation. 9. Exogenous proteins are taken up DCs. 10. They are degraded in endosomes and presented via the MHC II pathway. Moreover, to obtain cognate T-cell help in antigen-presenting cells, the protein should be routed through the MHC II pathway. 11. The generated antigenic peptide epitopes are subsequently loaded onto MHC II molecules. 12. The loaded MHC II-peptide epitope complexes are presented on the surface of cells, leading to the induction of the antigen-specific CD4 + T cell responses. Exogenous antigens can also be processed and loaded onto MHC class I molecules via a mechanism known as cross-presentation. (Link)

Now, The mRNA-1273-encoded prefusion stabilizes the S protein (Moderna Vaccine) consists of the SARS-CoV-2 glycoprotein with a transmembrane anchor and an intact S1–S2 cleavage site. The presence of the transmembrane anchor would seem to enable some of the spike proteins to remain attached to the surface of the cell that produced them, such as a muscle cell, but would still be recognized as “foreign” by the immune system. (Link)

See also: Link


Are mRNA Vaccines for COVID-19 helpful or harmful?
The following commentary by organic chemist Derek Lowe is also helpful in understanding this question (December 4, 2020):

Bob Wachter of UCSF had a very good thread on Twitter about vaccine rollouts the other day, and one of the good points he made was this one. We’re talking about treating very, very large populations, which means that you’re going to see the usual run of mortality and morbidity that you see across large samples. Specifically, if you take 10 million people and just wave your hand back and forth over their upper arms, in the next two months you would expect to see about 4,000 heart attacks. About 4,000 strokes. Over 9,000 new diagnoses of cancer. And about 14,000 of that ten million will die, out of usual all-causes mortality. No one would notice. That’s how many people die and get sick anyway.

But if you took those ten million people and gave them a new vaccine instead, there’s a real danger that those heart attacks, cancer diagnoses, and deaths will be attributed to the vaccine. I mean, if you reach a large enough population, you are literally going to have cases where someone gets the vaccine and drops dead the next day (just as they would have if they *didn’t* get the vaccine). It could prove difficult to convince that person’s friends and relatives of that lack of connection, though. Post hoc ergo propter hoc is one of the most powerful fallacies of human logic, and we’re not going to get rid of it any time soon. Especially when it comes to vaccines. The best we can do, I think, is to try to get the word out in advance. Let people know that such things are going to happen, because people get sick and die constantly in this world. The key will be whether they are getting sick or dying at a noticeably higher rate once they have been vaccinated.

No such safety signals have appeared for the first vaccines to roll out (Moderna and Pfizer/BioNTech). In fact, we should be seeing the exact opposite effects on mortality and morbidity as more and more people get vaccinated. The excess-death figures so far in the coronavirus pandemic have been appalling (well over 300,000 in the US), and I certainly think mass vaccination is the most powerful method we have to knock that back down to normal.

That’s going to be harder to do, though, if we get screaming headlines about people falling over due to heart attacks after getting their vaccine shots. Be braced.


Are mRNA Vaccines for COVID-19 helpful or harmful?
I know that various European countries, including the Netherlands, Denmark, and Spain, have reported outbreaks of COVID-19 in mink pelt farms – leading to the culling of more than a million animals. From laboratory experiments, it’s also clear that ferrets (a relative of the mink) are also readily infected with the “novel coronavirus”. Aside from this, however, I’m not aware of any “issues” with animal experiments regarding COVID-19 in particular. However, in 2008 there was an interesting experiment involving ferrets that were given the flu vaccine against the H1N1 virus – who then became sicker once exposed to the live virus as compared to those ferrets that weren’t vaccinated. The reason for the effect was unclear, and Skowronski, the lead author, urged other research groups to take up the question.

“Skowronski likened the mechanism to what happens with dengue viruses. People who have been infected with one subtype of dengue don’t develop immunity to the other three. In fact, they are more at risk of developing a life-threatening form of dengue if they are infected with one of the other strains.”

Skowronski called the second theory the infection block hypothesis. Having a bout of the flu gives the infected person antibodies that may be able, for a time, to fend off other strains; flu shots only protect against the strains they contain. So under this theory, people who didn’t have flu in 2008 because they got a flu shot may have been less well armed against the pandemic virus.”

While interesting, such an effect has not been identified in the animal or human trials for the mRNA vaccines against COVID-19. Also, subsequently updated flu vaccines to the H1N1 strain haven’t had this problem either (Link).


Recent Comments by Sean Pitman

Dr. Walter Veith and the anti-vaccine arguments of Dr. Geert Vanden Bossche
If you understood how these vaccines actually work, you would understand that they are part of helping to preserve life and health – part of ending all the death and suffering that the SARS-CoV-2 virus is causing on this planet.

Not all science is bad. Most of the discoveries of science are actually good – especially when it can be tested and observed in real-time. True scientific knowledge and medical advancements are a gift of God to ease the pain of humanity in this fallen world…


Dr. Walter Veith and the anti-vaccine arguments of Dr. Geert Vanden Bossche
I don’t know when Novavax will be approved? Here’s the latest on their clinical trials: Link


Dr. Walter Veith and the anti-vaccine arguments of Dr. Geert Vanden Bossche
I don’t know what is happening in Orange County, but I do know that the vaccines have not been approved for anyone under 16-years-of-age. And certainly, any medical procedure done on a child or a minor should first be approved by the parents…

That being said, I would certainly have my own two boys (9 and 11) vaccinated as soon as the mRNA vaccine is available for children.

Again, the evidence is very very clear that the risks associated with the mRNA vaccines are far far outweighed by the risks associated with getting the actual live COVID-19 infection where up to 1/3 of children sustain long-term/permanent injuries – not to mention the risk of passing it on to others who may also be die or be permanently injured.


Dr. Walter Veith and the anti-vaccine arguments of Dr. Geert Vanden Bossche
If that makes you more comfortable, that’s fine. However, when it comes to the mRNA vaccines, in particular, there really are no more remaining questions of any real seriousness to be answered. The technology has been around and studied for over 30 years now and the vaccine trials were a great success, demonstrating amazing efficacy as well as safety. The same has been true of the general rollout around the world. Those countries with the highest percentage of vaccinations are doing the best regarding a reduction in death rates and injuries from the COVID-19 virus. The longer you wait, the greater your personal risk and the risk to others around you.


Dr. Walter Veith and the anti-vaccine arguments of Dr. Geert Vanden Bossche

Can you talk about the blood clot side affect — the rash side affect — and the other side affects listed in the VAERS document? Are these deaths and suffering are just “ho-hum” dispensable humans to the cause of good for all?

I talk about VAERS here (Link). The Herpes Zoster rash happens in a low percentage of immunocompromised people who have previously been infected with the Herpes virus (Link). While certainly uncomfortable, it’s not life-threatening and it isn’t a risk for most people. The blood clot risk is a very rare risk (about 1 in a million for young women) for the DNA vaccines, possibly related to the adenoviral vector used for the vaccines. I talk about this here (Link). There is also a very rare risk for severe immune thrombocytopenia (Link). Note that for all of these risks for the vaccines, the very same risks are much much much higher when it comes to being infected by the live COVID-19 virus. So, if you want to reduce your risk as much as possible, the best way to do that is to get vaccinated.

What is happening to cause so many side affects? How is one to know if there is a chance of dangerous side affects of the vaccine for a person?

The thing about risk is that it is impossible to know, ahead of time, exactly how a particular person will react. That’s just the nature of the concept of “risk”…

Are vaccinated women who get the vaccine during pregnancy, or get pregnant and give birth having any side affects among their babies?

No. I talk about this rumor here (Link).

Also, have your children been vaccinated? What is your opinion of elementary or high schools requiring the vaccine for school children? Which childhood conditions need to be studied before administering the vaccine to children with these conditions?

The mRNA vaccines are not approved for children under the age of 16. They are currently in the trial phase of testing for younger children. My own boys are 9 and 11 years of age, so no, they haven’t been vaccinated yet. However, once approved, I would be getting them vaccinated since even children are at risk for long-term injury and sickness from COVID-19 (30% of children get Long-Hauler’s following even asymptomatic infections with COVID-19). As far as childhood “conditions”, I know of no common childhood conditions which would preclude vaccination…

What “empirical evidence” is there that mRNA vaccines do not cause any side affects “a year or two or three down the line”? Is there a study I can read – link?

As I’ve already mentioned, the evidence for this is the very long history that we’ve had with vaccines and understanding how they work with the human immune system. When complications arise, they do so within the first few months for large populations (Link). It is extremely unlikely that something brand new and unexpected will come to light years down the line (Link). Also, by that time, millions will have been killed and permanently injured by the very real and very well-known risks of the COVID-19 virus itself.

Yes, your glowing recommendation is convincing with several issues not addressed in the glow.

I have addressed most of your questions already in other posts on this topic…

Do you recommend a yearly booster vaccine like now is being developed? I think big Pharma announced a flu/covid combo vaccine coming out for next fall. What is your opinion please?

For now, it seems likely to me that the mRNA vaccines will produce immunity lasting more than a year, likely several years. However, as with most viruses, the COVID-19 virus mutates. If a new mutant strain comes along that “breaks through” the immunity provided by the original vaccine(s), then yes, a booster would be necessary. However, if enough people would get vaccinated quickly, it would make the odds of such breakthrough mutations less likely.

Thanks for your help in understanding the full spectrum of topics about these mRNA vaccines.

Thank you for your thoughtful questions.