The new paper showing the spike protein is found in armpit lymph nodes at least 60 days after vaccination also shows that immune imprinting from vaccination leads to “original antigenic sin.”
This is not medical advice. See full disclaimer at the bottom.
The new paper in Cell showing that the spike protein persists in the lymph nodes of the armpits at least 60 days after vaccination also suggests that vaccination impairs the response to variants of concern.
Bizarrely, the “Highlights,” “Summary” and “Graphical Abstract” all suggest the opposite.
The “Highlights” report that “Vaccination confers broader IgG binding of variant RBDs than SARS-CoV-2 infection.”
The “Summary” reports that “Antibody breadth against viral variants is lower after infection compared with all vaccines evaluated but improves over several months.”
The “Graphical Abstract” reports that “COVID-19 Patient Cohorts” display “less broad variant recognition” while “vaccinee cohorts” display “broader variant recognition.”
Actually, this isn’t bizarre. It just betrays that in the era of COVID, authors systematically highlight their work in ways that create a bias toward concluding vaccination induces superior immunity to infection, even when the central findings of their paper suggest the opposite.
What they actually found was the following:
- Infection with the original Wuhan strain does everything they attribute to natural infection in their highlights, summary, and graphical abstract. It creates immunological imprinting specific to the Wuhan strain with an even greater bias than that created by vaccination. Why an even greater bias? I return to this question later.
- Vaccination, however, is always against a spike protein based on the Wuhan strain, and thus also creates this bias.
- Getting vaccinated prior to getting a variant makes the immunity you get to the variant biased toward the Wuhan strain. For example, if you get vaccinated before you get delta, your immunity to a second infection with delta will be much weaker than if you had gotten delta without getting vaccinated because the imprinting from the vaccine caused “original antigenic sin.” That is, it made your immunity biased toward the Wuhan strain even when later boosted by variants.
Original Antigenic Sin
This is summarized perfectly in Figure 5B:
Those who had never been vaccinated at the time they were infected with the delta variant developed immunity with a strong preference toward the delta variant.
Those who had only been vaccinated had immunity with a moderate bias for the Wuhan strain over delta.
Those who were vaccinated and then infected with delta developed immunity that moved somewhat delta-ward, but barely. That immunity looks much more like vaccination alone with its moderate preference for the Wuhan strain than with the strongly delta-biased immunity created by infection with delta alone.
Booster shots did not appreciably change the magnitude of the bias toward the Wuhan strain (Figure S5B), but did bring the declining levels of antibodies found 3-4 months after vaccination back up and even slightly above their 3-week peak (Figure 1A). Thus, booster shots restored the original degree of immunity without doing anything to its bias toward the Wuhan strain.
This persistent bias toward the strain of original exposure was termed “original antigenic sin” in 1960 in the context of influenza responses. It reflects a “first dibs” effect where the original infection or vaccination has the greatest degree of immune imprinting.
What About Boosting With Variants Versus Vaccines?
This paper does not look at those originally infected with one variant and then infected with another. For example, someone never vaccinated but first infected by delta and subsequently infected by omicron. Presumably, that person’s “omicron boost” would raise total antibody levels back to or above their peak much like a booster shot and, though they would largely retain the delta bias of the first infection, they would push it omicron-ward. As a result, post-omicron immunity would reflect a blend of delta and omicron biases, with the delta bias being the stronger of the two.
This paper also does not examine what happens when someone gets a booster shot after being infected with a variant. Presumably the booster shot would raise total antibody levels back to or above their peak, but would restore the bias to the Wuhan strain.
This suggests a fundamental difference in perpetual boosting versus perpetual natural exposure:
- In the context of natural immunity, continued “boosting” through exposure to dynamically evolving variants causes dynamically evolving immunity that is always anchored to the bias of the first infection but is gradually nudged toward protection against all of the variants.
- In the context of perpetual booster shots, the original bias toward the Wuhan strain is reinforced with each booster, impairing immunity to the evolving variant landscape. Even if one is infected with a variant, the next booster shot erases any nudge toward immunity to that variant and pushes it back to the original Wuhan bias.
The authors suggest that the high levels of antibodies generated by perpetual boosting “may be able to compensate for relatively decreased binding to new variant antigens, potentially decreasing the public health impact of antibody response imprinting if vaccine boosting is widely adopted.”
However, the long-term antibody response of natural infection is just as strong as vaccination and includes a wider breadth of targets (Figure 2B).
Why Does Natural Infection With the Wuhan Strain Create a Stronger Wuhan Bias Than the Vaccine?
That the “original antigenic sin” of being infected with the Wuhan strain is even greater than the “sin” of being vaccinated against it is a puzzle.
The authors do not solve it definitively, but they have a suggestion: since the spike protein is found in the lymph nodes of the armpits of vaccinees for at least 60 days after infection but is rarely found in those recovered from COVID at all, there is less pressure for the vaccine to develop highly specific antibodies to it.
To grasp this, we need to understand “affinity maturation.” The immune response to any vaccination or infection always starts out with low-specificity antibodies. During affinity maturation, antibody-producing cells reproduce with an extremely high mutation rate. The immune system uses fragments of whatever it is trying to fight off to test the specificity of the antibodies from the resulting cells. Highly specific antibodies are rewarded with chemicals that cause the cells to reproduce faster. Less specific antibodies are punished by killing off the cells making them.
If the immune system is trying to use spike proteins to test the specificity of antibodies but there is very little spike protein to go around — as after natural infection — then it will be harder to find specific antibodies and only the most specific — only the A list — will win. By contrast, if there is abundant spike — as after vaccination — then it will be easier to find specific antibodies and a larger portion — even the B list — will make the cut.
It is this principle that led to the claims in the highlights, summary, and graphical abstract that vaccinated people have “broader variant recognition” than those who have been previously infected. What they left out is that this statement only applies to those infected with the original Wuhan strain. This statement has little relevance given that the Wuhan strain no longer circulates, and those infected by variants have much better recognition of the variant than vaccinated individuals do.
This principle does, however, raise a question: does this “broader variant recognition” compared to those infected with the Wuhan strain, since it is thought to derive from the long-term persistence of spike protein within the body of vaccinated individuals, come at the expense of spike protein toxicity?
Tomorrow I will examine in greater detail the possibility that the spike protein from the vaccines is directly toxic.
No Analysis of Mucosal IgA
These authors did collect saliva samples, which are often used as representative of mucosal samples in general, and thus could be used as a proxy for the mucous membranes of the gut, lungs, nose, and eyes. However, they did not measure salivary IgA.
As I covered in Explaining the “Hospitalization Paradox,” natural immunity is overwhelmingly based on local mucosal IgA as its first line of defense. There is no local mucosal IgA response to intramuscularly injected vaccines. Excluding mucosal IgA from any study comparing natural immunity to vaccine-induced immunity is ignoring the primary strength of natural immunity and creating a systematic bias toward the vaccines.
The maturing of the antibody response of the nasal mucosa occurs locally in the the nasal-associated lymphoid tissue. Since natural exposure begins through the mucosa of the eyes, nose, or mouth, and usually does not lead to systemic exposure, it is possible that the mucosal IgA would be more versatile in responding to new variants than would systemic antibodies circulating in the blood.
If the authors are correct that an abundance of spike protein leads to broader specificity of the antibodies, then mucosal IgA should be very broad indeed. Spike protein is found almost exclusively in the mucous membranes of the respiratory tract, mouth, nose, and eyes in natural infection, and is most abundant in the nose and lungs. The mucosal IgA of naturally infected individuals should have much broader recognition of variants than the systemic antibodies circulating in the blood of those same naturally infected individuals, as well as those circulating in the blood of vaccinated individuals.
I therefore suspect this study radically underestimates the superior ability of natural immunity to dynamically evolve with variants.
This is not an argument to go out and get infected. However, we should be open to the possibility that if one has already developed strong immunity against severe illness, continued low-dose exposure to even milder variants makes much more sense than trying to achieve zero-COVID. By contrast, perpetually boosting the Wuhan strain seems incredibly foolish.
I am not a medical doctor and this is not medical advice. My goal is to empower you with information. I will not take a position on whether you should or should not get vaccinated. Please make this decision yourself, consulting sources you trust, including a caring health care professional. Please do not construe anything in this article as a recommendation to become purposefully infected.
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