Boosters: Important Considerations

Timing is Important

There is a common issue that keeps coming up in the various COVID support groups, and among those speaking out against vaccines. People are reporting an autoimmune response after taking the boosters. The studies point to timing and another potential reason this is occurring. First, we have to understand how COVID and to a lesser degree, vaccines impact the immune system.

What happened to antibodies?

Antibodies, which are proteins that attach to the virus and stop it from entering cells and causing infection, are no longer sufficiently preventing infection. This study on the XBB variant said, "We demonstrate that these convergent mutations can cause striking evasion of convalescent plasma, including those from BA.5 breakthrough infection, and existing antibody drugs, including Evusheld and Bebtelovimab.” XBB and XBB.1.5 took out the last available monoclonal antibody treatments. There is still one that is currently unavailable that shows neutralizing capability, but let’s be realistic, if approved, once that is put into use with a high prevalence of transmission, the evolutionary advantage goes to the virus finding a workaround.

XBB and XBB.1.5 can evade antibodies from the BA.5 booster and a prior infections.

• "Although BA.5-bivalent-booster elicits better neutralization than parental vaccine, it does not produce robust neutralization against the newly emerged Omicron BA.2.75.2, BQ.1.1, and XBB.1.”(1)

• ”BQ.1.1, BM.1.1.1, and especially XBB, are the most antibody-evasive strain tested, far exceeding BA.5 and approaching SARS-CoV-1 level.”(1)

• ”Strikingly, the BJ.1/BM.1.1.1 recombinant strains XBB and XBB.1 (XBB+G252V) are among the most humoral immune evasive strains tested, comparable to those of CH.1.1, BQ.1.1.10, and BA.4.6.3.”(2)

• "A fourth dose, a bivalent mRNA vaccine targeting Omicron BA.4/BA.5 and an ancestral SARS-CoV-2 strain did not induce superior neutralizing antibody responses in humans, at the time period tested, compared to the original monovalent vaccine formulation."(3)

• “Previous infection enhances the magnitude and breadth of BA.5-bivalent-booster-elicited neutralization. However, this may be mainly driven by the enrichment of NTD-targeting antibodies after BA.5 breakthrough infection, which was also reported in BA.2 convalescents . Therefore, the effectiveness of BA.5-based boosters against the convergent mutants carrying critical NTD mutations should be closely monitored."(4)

The last point notes that we should keep a close eye out for new mutations. Most countries have scaled back their genomic sequencing efforts. We should scale up efforts.

Despite the low percentage of sequencing the U.S. is doing, the U.S. still provides a large amount of data on the circulating variants compared to other countries.

If the antibodies are evaded, then what are we relying on?

The pressure falls on the thymus and the lymphatic system to produce T cells that can kill the virus after it infects our cells. “T lymphocyte cells (T cells), a type of white blood cell, do not to stop a virus from entering cells as antibodies do, but to prevent the dissemination or propagation of the disease. T cells essentially kill infected cells, decreasing the severity of the disease. Importantly, researchers are confirming that T-cell responses kick in regardless of how SARS-CoV-2 mutates.”(3)

The benefit of taking the booster at this point is to build on the existing T-cell response from a prior infection and/or vaccine induced.

How Do T-cells Work

Immunity now depends on T cells, and there are two main types of T cells that protect us: naïve T cells and memory T cells. Naïve T cells are the new additions to the immune system. They have never fought or been exposed to pathogens, and they are processed into various types of T and B cells to help protect against new infectious agents. On the other hand, memory T cells are like the highly trained warriors, often scarred and toughened by fighting off harmful invaders. As soon as puberty starts, naïve T cell production in the thymus ends and they get used up as life progresses. This makes older people more likely to get sick, especially from new pathogens like COVID, because our bodies have to build a new army out of the naïve T-cells. Repeat infections that kill large numbers of memory T-cells are aging people on a cellular level.

Do young and healthy people benefit from taking a 3rd or 4th booster?

1. In this smaller study on younger adults, who were capable of mounting a good immune response, they collected blood from 31 people who got the mRNA vaccines bnt162b/Comirnaty (Pfizer) or mRNA-1273/Spikevax (Moderna) three times and five people who got a fourth shot. Before getting the vaccine, anti-SARS-CoV-2 nucleocapside IgG serology showed that none of the people who got it had ever been infected with SARS-CoV-2. Also, blood was taken from 13 people who got SARS-CoV-2 infections after their third mRNA vaccination. Positive PCR testing from an oropharyngeal swab showed that they were new infections. All 13 people in this study who got new infections had mild symptoms and did not have trouble breathing.

“Spike-specific CD8+ T cell frequencies had already reached their set point approx. 60 days after the 2nd dose and were rapidly boosted with peak expansion one week after the 3rd dose in all tested donors”(4)

After the 3rd dose, all reached the same level as after the 2nd dose within one week. Within 30–60 days, the number of activated, proliferating, and differentiating spike-specific CD8+ T cells in the blood quickly went back to where they were before the 3rd dose, following the same pattern as after the 2nd dose.

An infection after the 3rd dose and after the 4th dose without an infection, the early T cell memory was fully functional and had the same reactivation capabilities, including growth, cytokine production, and degranulation. “The frequencies of the BCL-2hi memory pool within the spike-specific CD8+ T cells were stable before and after the 4th antigen contact irrespective of breakthrough infection or 4th vaccine dose. Hence, vaccine-elicited spike-specific CD8+ T cell immunity exhibited a substantial recall capacity in vivo even towards VOCs such as Omicron.”(4)

“Our study highlights that mRNA vaccines are potent inducers of a robust, functionally competent, and durable spike-specific CD8+ T cell immunity already after completing basic immunization." (4) In other words, as far as T-cells are concerned, the boost was short lived without an active infection, and thanks to the memory T-cells, the response would occur, although slightly slower, if someone was previously infected, and/or took 2 primary doses of an mRNA vaccine and didn’t take the booster. Without knowing when that next infection may come, it is not feasable to time the booster dose for the 2 month window in which it produces the optimal immune response. Sounds good but we have to answer another question.

There is stable memory T cell response irrespective of booster immunization, but how long do memory T cells stay in circulation?

Here are some studies that answer this question at different time points.

• “These findings demonstrate robust cellular immune memory to SARS-CoV-2 and its variants for at least 6 months after mRNA vaccination.(5)”

• Immunological memory to SARS-CoV-2 assessed for up to 8 months after infection

  “Memory CD8+ T cells and memory CD4+ T cells declined with an initial half-life of 3 to 5 months. This is the largest antigen-specific study to date of the four major types of immune memory for any viral infection."(6)

• T-cell responses were detected up to 10 months after initial COVID-19 infection with 90% sensitivity. (7)

If we accept that antibodies are evaded and the circulating memory T-cells provide a sufficient immune response to avoid severe disease, while not stopping infection or long-term organ damage, then waiting the 6 to 10 months until the T-cells begin to wane after an infection or vaccination to boost them back up makes more sense.

1. How do you know if you were infected or not? Asymptomatic or mild symptoms occur in up to 80% of children and anywhere from 30% to 50% of younger adults. Many are not testing themselves and if they do, they are often getting a false negative results. The odds are very high that a healthy and active younger person will be infected at some point in 6 to 10 months without any mitigation protections. Under 35 would likely benefit if they could know if they were infected, however, due to the negligent, and incoherent CDC and Whitehouse response, if under 35 years old, it may not be worth the risk. That does NOT mean the odds of long-term organ infection became any less. The opposite is true.

   If 15 to 55 years old, seriously reflect on this.

   In 2021, COVID was the #4 cause of death of 15 to 35 year old's. The #2 cause of death of 35 to 45 year old's, and the #1 cause of death of 45 to 55 year old's. Likely to increase in 2022.(8)

2. To find out if you were COVID positive in the prior 6 to 10 months, there are both antibody tests and T-cell tests available. Antibody tests can only detect for two to three months. T-cell test can detect up to10 months, but they aren’t cheap. None the less, that would be the surest way to know when to take a booster.

3. You decide that you weren’t infected, and want to take a booster. Based on the science and data presented thus far and below this point, the hypothesized, preferable time to increase memory T cell responses while using fewer naïve T cells is to wait at least six months but not more than ten months after the last shot or infection.

Will the memory T-cell response be as strong or last as long in an older adult, someone who has a persistent (chronic) infection or is already immunocompromised?

Naïve T-cells are processed through the thymus. The thymus is very sensitive to things, like stress, acute infection, and age related thymic involution. It is also very sensitive to long-term damage, from chronic, persistent infections, like COVID, which are occurring with ever greater frequency. If the virus gets into the thymus directly or indirectly by infecting cells in the periphery, the immune system could be damaged. This could make it harder for the body to fight off future infections.

“Shrinkage of the naïve T cell compartment in size and diversity with age will therefore have a negative impact on the generation of memory cells." (6)

“The human TCR repertoire remains very diverse in older healthy individuals, although it loses in richness and, perhaps more importantly, displays shifts in clonal size distributions with increasing clonality and increasing autoreactivity" (6)

The older someone is, from 35 years old, or if they are immunocompromised or have already had thymus damage from prior infections that bypass antibodies, the slower the thymus may operate, resulting in fewer memory T-cells and a slower response to new infections. The odds of autoimmune reactions occurring in all of these scenarios increase. The memory T Cell response may not be as strong or last as long.

Damned if you do, damned if you don’t.

People who have had repeated infections, are older, or are immunocompromised may already be processing T-cells slower, have fewer naïve T-cells left, and can have an increased risk of autoimmune reactions. COVID variants can make all of this much, much worse. To a significantly lesser extent, the mRNA vaccines can also cause autoimmune reactions because they use up more naïve T-cells and/or get the old warriors, the memory T-cells, agitated causing an autoimmune response. The argument could be made that if someone in any of these conditions is taking every precaution, and not in situations with a lot of people, then a booster increases the risks, when they are unlikely to be infected. That approach is risky, because people get infected despite their best efforts but reserving a booster for big family or social events, like over the holidays, might make more sense. It would decrease the wear and tear on the immune system, potentially extending their lives. The taxpayer funded, free vaccines, likely won’t be available after September 2023, when the last batch ordered expires. They should still be available to purchase or through insurance.

If you are in a situation that puts you around a lot of people often, then waiting a minimum of seven months and not more than 11 months after the last shot or infection is likely the best scenario.

This is a truly tragic situation facing millions of people. Forced to face COVID without a vaccine or take a vaccine that comes with its own risks. The only other option, at this point, is to seriously reconsider putting yourself in those situations.

Note: The U.S. govt has not ordered more and the last batch, delivered in December 2022, will expire in September 2023.(11)

A hypothesis on the root cause of vaccines adverse reactions,

including vascular dysfunction.