Why I Will Not Get a COVID-19 Vaccine
I believe the current versions of SARS-CoV-2 vaccines are poor, and it was always inevitable that they would become poor because of slow global vaccination rates and a use of a single, highly mutable gene, S, which makes escape easier.
https://www.sciencemag.org/news/2021/08/grim-warning-israel-vaccination-blunts-does-not-defeat-deltaFurther, they will probably only get worse given the rate of evolution in SARS-CoV-2 today. That rate is likely to only accelerate unless we get R below 1 for all strains, which is nearly impossible if we're starting from R0's around 8. There looms the spectre of antibody-dependent enhancement(ADE), which is a property of other betacoronaviruses.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943455/I think other vaccines hold better promise and will not need to be administered nearly as frequently because they target other parts of the immune system or virus, and their safety profile and durability are better understood. We're already staring down likely endless 6-8 month booster shots for COVID-19 vaccines, a period which should shorten. I am afraid of original antigenic sin(OAS).
Full FDA approval is an arbitrary stamp in the face of legitimate scientific concern. I'm not afraid of infrequent side effects, although the inherent pathogenicity displayed by N(which isn't included in today's vaccines, but we may try to target it as S drifts) and S1 are warning signs that even exposure through vaccination may be risky. We do not understand the proteome nor pharmacokinetics well enough to know yet.
Let's start with a recent review of potentially repurposeable drugs and vaccines:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8101866/In particular, there have been very encouraging findings in papers on MMR II, poliovirus, and pertussis vaccines. The titers of antibodies against the mumps strongly inversely correlates with SARS-CoV-2 disease severity, though through unknown mechanisms; the antibodies themselves have been identified as non-cross-reactive, so T-cells, with their large epitope pool, are a good guess. Pertussis' mechanism of action has also yet to be elucidated, but it is likely to be similar, as the antibodies are also non-cross-reactive. Poliovirus vaccines work by targeting SARS-CoV-2 RdRp, which is much more conserved than S. IPV is in clinical trials now.
https://www.medrxiv.org/content/10.1101/2021.06.19.21257191v1.fullhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7596387/
https://journals.asm.org/doi/10.1128/mBio.02628-20
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0241471
BCG holds great promise, but it appears to work through altering the innate immune system over time and changing cytokine profiles, so it takes several years of inoculations to become superior to IPV. Both would be ideal, but BCG can't provide much immediate help.
https://www.jci.org/articles/view/133935I believe these are better than the mRNA vaccines. They last way longer, have similar efficacy profiles against variants of concern -- the only type of variant you're likely to encounter these days -- have more and better targets(at a minimum, RdRp/nsp12, a key enzyme in viral replication, rather than S, which mutates at 6.5x the rate of the rest of the SARS-CoV-2 genome and is under heavy selective pressure right now from all the vaccinations; RdRp is so highly conserved that poliovirus RdRp is sufficiently homologous to SARS-CoV-2 RdRp that the antibodies are cross-reactive). They have better safety profiles. I do not face the same risk of homologous non-neutralizing antibodies causing ADE nor OAS.
Moderna isn't even yet recruiting participants for their new mRNA-1273.351, which targets the Beta S protein, and Pfizer similarly hasn't released their version of BNT162b2 targeting Delta. We're going with booster shots of the original instead even though it's very easy to redesign the mRNA vaccines and the vaccines' current efficacy against infection and transmission by Delta is bad.
Ask yourself, what's up with that? I have two hypotheses: OAS, which I favor, and antigenic drift.
Antigenic drift:SAGE recently found that Delta serum does not confer meaningful protection against Beta/B.1.621 virus. This indicates that, as SAGE earlier predicted, sufficient antigenic drift has occurred since the beginning of the pandemic such that only a bivalent vaccine can provide good protection today, and that we're already actually fighting 2 separate pandemics, not 1. The only reason the current vaccines are modestly effective against both is that they're built around the original S protein, which lies in the middle of the radial phylogenetic tree of SARS-CoV-2. It has already been demonstrated that two points on the tree are too far apart, and one of them happens to be Delta, and one of them happens to be Beta. Eventually, that tree should grow too large for any single point to reach all the others, and then any pair to encompass all points, and so forth.
We will not be able to address this for long through increasing the immunogenicity of the vaccines because the virus has already selected at least two qualitatively different methods of immune escape. Delta increased the distance between two beta sheets in the RBD by 1.5 angstroms, making the energy required for antibodies to inactivate the virus greater. Beta, B.1.621, and others directly modified their epitopes and relied on electrostatic, hydrophobic, or other properties to make antibodies unable to neutralize or bind. We do not know how many other qualitatively different paths there are out there, but it's safe to assume, "a lot." I could throw in a glycan shield as one obvious viral countermethod.
https://www.biorxiv.org/content/10.1101/2020.12.28.424451v1This is only a fatal issue if the tree grows faster than our ability to administer polyvalent vaccines successfully, which ultimately hinges on viral evolution rates, vaccine administration logistics, and OAS. After all, we could be administering bivalent vaccines shortly: mRNA-1273.211, a 50:50 mix of mRNA-1273.351 and mRNA-1273, is currently under evaluation by Moderna.
Such a vaccine will shroud our view of OAS, which could be why Moderna is moving ahead with the bivalent version rather than mRNA-1273.351 alone. The other would be knowing that mRNA-1273.351 would be unlikely to be very protective against Delta, and should be favored as an explanation, as it would also explain Pfizer's delays with its Delta vaccine: it wouldn't protect against Beta-serotypical strains well.
https://clinicaltrials.gov/ct2/show/NCT04927065OAS:
There is no definitive proof of OAS in SARS-CoV-2, but it's almost impossible to imagine it's not strong. The mRNA vaccines produce a huge pool of memory B cells and Tfh cells that will make it hard for anything new to get out of germinal centers. Thus, how significant OAS will be will ultimately depend on how long the B and T cells last(indications are decades), and how fast the virus alters its immunodominant epitopes. I suspect it will be a big issue, and if it is, it will be catastrophic to people who have received today's COVID-19 vaccines. At a minimum, I will be avoiding any S-targeting vaccine until antigenic drift has slowed.
https://pubmed.ncbi.nlm.nih.gov/33692194/Finally, I always wear an N95 mask in indoor settings and in most outdoor settings. There is no substitute for non-pharmaceutical interventions.
None of this is new. I refused to receive the vaccine when it was first offered to me early because my wife works in health care. I'm just too scared of expressing different opinions in today's censored, obsequient world. I will continue to refuse the vaccine even as my civil rights are rapidly stripped on the bases of poor science and profiteering. I'm just forced to talk about it now because the government, corporations, and rogue scientists of the Daszak genus are being so deceitful and forceful. One only has to look at the recent opioid settlement for the appeal to authority to fail.
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