A science news article in Phys.Org was floating around social media this week, with a headline that is a bit misleading. The article was titled, “Immune responses support COVID-19 vaccination regardless of when people were infected” (https://medicalxpress.com/news/2022-04-immune-responses-covid-vaccination-people.html). The news report refers to work contained in an article published in Nature Immunology by researchers at St. Jude’s Children’s Hospital and the claim is that individuals who have already had COVID-19 still see expanded T-cell memory and immune activation after vaccination and therefore, “immunity by infection is not better than vaccination.” OK, that’s fine, but it doesn’t really “support vaccination” any more than it supports remaining unvaccinated. It provides some information that might aid someone in making a choice. Before delving into the study itself, I want to draw your attention to the ongoing semantics dance. As vaccine mandates were being rolled out, one of the most commonly used arguments against them was the fact that those who had already had an infection did not need the vaccination because they already had immunity. As the vaccine enthusiasts pushed back against this argument, the fact that natural immunity is often superior to vaccine-induced immunity was raised, and this opened the door for the powers-that-be to focus on whether natural immunity was, in fact, proven to be superior to vaccine-induced immunity. Let’s put aside for a moment the fact that “better immunity” has no set definition and some studies focus on antibodies, others on T-cell memory and others on epidemiological evidence for re-infections vs breakthrough infections. Even if you could prove vaccine immunity to be “as good” as natural immunity, that doesn’t justify demanding those who have had prior infections be vaccinated. The public health complex has, once again, flipped the scientific method on its head and demanded that the new paradigm be embraced until it can be disproven. Now let’s look to see if the article even provided strong evidence that vaccine-induced immunity is as good as natural immunity.
The article, entitled, “SARSCoV2 antigen exposure history shapes phenotypes and specificity of memory CD8+ T cells” (https://www.nature.com/articles/s41590-022-01184-4) looked at cytotoxic T-cell responses in blood collected from people who had been exposed to SARSCoV2 antigens by a primary infection only, primary infection then vaccination, vaccination only, or a “breakthrough” infection after vaccination. They used a high throughput technique that allowed them to look at over 4000 epitope-specific T-cell responses, which is the coolest part of this study. To make it clear what they did in this study, and what it means, I’ll give a quick background on the basic immune response. Skip the next paragraph if you know your immunology.
When the body is exposed to a pathogen like a virus, there are cells called antigen presenting cells (APCs) that are constantly surveying their environment and they engulf the virus, break down its proteins and present little pieces of them (antigens) on the surface of their cells attached to a protein called MHC-Class II. These are recognized by lymphocytes called T-helper cells, and this results in an immune response specific to that antigen. One of these responses is triggering a different type of lymphocyte (B-cells) to produce antibodies. B-cells bind to a specific region of the antigen (called the epitope) and produce antibodies that recognize that little sliver of protein. Because the virus has many different proteins, many different antigens will be presented to the immune system and the antibody response will be diverse. Other responses that result from the T-cell activation involve cellular signals that play a role in the overall inflammation. A second thing that happens with a viral infection is that, after the virus invades cells, it copies its genome and uses your protein machinery to make its proteins that eventually get packaged back into new viruses. While that protein expression is going on, some of those proteins are sent to a degradation pathway inside the cell and broken down into little pieces that are then presented on the surface of the cell on a protein called MHC Class I. All of our cells have MHC Class I, whereas only specialized cells make MHC Class II under normal conditions. The MHC Class I proteins that are presenting viral antigens alert the immune system that the cell has been infected and a different type of T-cell called a cytotoxic T-cell will attack the infected cell so it cannot continue to serve as a source for the virus to replicate. Attenuated or inactivated viral vaccines, like most of the childhood ones you had, trigger both MHC class I and MHC Class II responses; the same is true when you get infected. An mRNA or DNA vaccine, that directs expression of a specific protein (like spike in the case of COVID vaccines) in a cell would be expected to only trigger an MHC Class I response. However, according to the literature, these mRNA and DNA vaccines were designed to result in both MHC class I and II responses, although it is somewhat difficult to find a thorough molecular mechanism of this. It appears to involve removal of a portion of the spike protein from the surface of cells after the mRNA is translated such that it can be taken up by APC’s and presented to T-helper cells. That long explanation is provided so that you can understand the significance of looking at so many different epitopes, why it is revealing that they only looked at cytotoxic T-cells not T-helper cells, and how these endpoints reflect “immunity”.
The study followed 55 individuals using St. Jude’s “tracking of viral factors associated with covid 19 (SJTRC)” system. 16 of the 55 never tested positive and 30 were diagnosed as SARSCoV2 positive with mild disease and had recovered before the vaccination; 9 developed infections after both vaccinations. All groups received two doses of the Pfizer vaccine and samples were collected prior to vaccine administration, after each dose, and after resolution of breakthrough infections. The group they call “vaccinated only” consisted of the 16 individuals that never developed an infection from whom they only collected samples after the second dose (there was no unvaccinated group in this study). They took blood samples prior to the first vaccination from 16 of the 30 people who had recovered from an infection and called that group “infection only”. They took samples between the two vaccine doses from the other 14 people who had previous infections and call that group “infection-vax1”. They took samples from all 30 people who had a previous infection after the second vaccine and call that group “Infection-vax2”. (So, there are 2 samples collected from the 30 people with prior infections which is how they have more data points than people. There is nothing wrong with this-it’s just confusing.) The samples from the 9 individuals who developed breakthrough infections are called “vax-infection”. The goal was to see if there was a difference in the response between people when they had different types of exposure to SARSCov2 antigens.
They first measured antibodies to the receptor binding domain (RBD) of Spike-the region against which the vaccines are designed to stimulate antibody production, and show a small but statistically significant increase in antibodies to this epitope in the vaccinated vs infection-only group. (Note that this endpoint is what is often cited by people claiming the vaccines work “better” than natural immunity. They work better at directing specific antibodies to the epitope contained in the vaccine-which is not the same as “working better” at protecting from infection.) They then look specifically at cytotoxic T-cells. To do this they isolate blood cells from each sample and then mix them with small beads coated with an array of different possible SARSCoV2 epitopes which allows them to physically isolate the “Covid-primed” T-cells (because they will bind to the epitopes on the beads), without the need to know what specific antibodies are produced. It’s a cool technique and makes it easier to analyze T-cell populations. With that assay, they saw no difference between any of the groups-whether the samples were collected before or after vaccination. This means that what the news article was trying to pitch as a “vaccination recommended” message was really just evidence that right after you get vaccinated, you have a similar T-cell response as you do with a natural infection. You could say it argues that, with respect to these endpoints, natural immunity is not better than vaccine-immunity. But that should not be used to argue for mandates or even subtle pressure.
Using a very elegant method for sequencing the specific epitopes and identifying which blood samples corresponded to a specific epitope, they made a very interesting observation that 5 of the most abundant antibodies were to epitopes that were also found in other coronaviruses, supporting the long-tossed about theory that some people may have weak cross-immunity to SARSCov2 from other coronavirus infections (and vice versa). This same analysis showed that vaccination after infection, and infection after vaccination, resulted in a diverse T-cell response. The vaccine in the absence of infection, resulted in an increase in spike-specific T-cell memory compared to those who only had an infection. That is not surprising; if they didn’t, one wouldn’t expect the vaccines to have ever made it to the clinic. As far as pushing the vaccine narrative, this study just shows that vaccines don’t prevent the body from having a diversified immune response to an infection, and that if you get vaccinated after infection, your spike-specific antibody production is enhanced. There are no data in the study that suggest vaccines are superior to natural immunity. They do not even look at T-helper cell responses, which one would expect to be better in the infected group than the vaccine only group. The authors also do not address whether the two (vaccines and natural immunity) are equally effective at preventing infections, as the study is limited to addressing one specific aspect of the immune response.
An interesting side point was that it did not appear that any of the 30 individuals that had previous infections developed a second infection, while 9 of the 25 participants that had not had a previous infection developed break-through infections. In other words only 16/25 (64%) participants entering the study without prior infection were protected from infection during the course of the study, despite being vaccinated. The article does not really address this component of their data. This is not to suggest anything dishonest, as the objective of their study was to examine cytotoxic T-cells. The take-home point is that the study shows a more diversified cytotoxic T-cell response than one might have expected from the vaccine which is a positive for anyone that really needs protection against COVID and would have a tough time with an infection. However, this study is irrelevant for anyone that simply wants to force other people to take the vaccine and suggests that for people with natural immunity, there is no significant value in getting the vaccine.
There seems to be no lack of these articles studies where the data doesn’t quite match the headline. Appreciate you taking the time to dig into the data and point out the truth.
Thank you for making this easier to understand for people like myself who need Immunology 101 language. What I’d really like to know is the timing on these post-vaccine sample collections. I’m guessing the collected 2-4 weeks post vaccination and surely it was stated in the study (just wasn’t the focus of your article). I wish they had collected and tested at three different intervals post-vaccine (1 week post, 2 or 3 weeks post, and 6 months post) to compare.