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There are a number of reasons why those who survive SARS-CoV-2 infection can expect to have longer-lasting immunity than those who have received vaccines, especially for the spike-protein-only vaccines. First, and most importantly, the spike protein has fewer immunogenic epitopes than the entire SARS-CoV-2 virus. These epitopes provide a diversity of nAbs and a diversity of memory B- and T-cells. Therefore, if immunity from infection conferred by the spike protein epitopes fails, those with prior infection will have redundant, back-up immunity. As I reported in April 2020, there were 54 immunogenic epitopes in the original SARS-CoV-2 proteome. That number has been expanded.
As evolutionary pressure against the spike protein pushes it away from being neutralized by vaccine induced antibodies, the virus cannot escape due to the other antibodies. The multiple components that contribute to fitness now make the adaptive landscape highly complex; from the virus’ evolutionary point of view, mutations that confer protection against nAbs that bind the spike protein do not also confer protection against nAbs that bind, for example, the M protein.
Similarly, mutations that confer protection to the virus from nAbs that bind the M protein do not also confer protection to the virus against nAbs that bind the SARS-CoV-2 endoRNAase.
Similarly, mutations that confer protection to the virus from nAbs that bind the endoRNAase do not also confer protein against nAbs that bind the SARS-CoV-2, helicase, leader protein, or matrix protein. This redundancy is really a numbers game: the probability that evolution will be able to co-localize all of the immune escape mutations into a single virion is exceedingly low, and decreases multiplicatively as the number of antigen sources are increased.
This Means Boosters with the Same Viral Protein Will be Ineffective and Massively Wasteful
The entire world seems focused on neutralizing antibodies. In a study of “waning immunity” following SARS-CoV-2 infection, the authors focused primarily on antibodies and suggested that re-infection or vaccination might be expected to produce prolonged immunity by keeping antibody levels up. They found that while nABs declined, that memory T- and B-cells increased and thus their estimate of the durability of immunity are likely conservative. However, the productions of neutralizing antibodies by itself is not a measure of immunity against an evolving virus: high nAbs are expected to be produced even in patients in whom first-round immunity has waned. See; "Prospects for durable immune control of SARS-CoV-2 and prevention of reinfection".
To boost the immune system to produce more antibodies that do not work is madness.
Those who are vaccinated will simply experience of boost in nAbs against the original SARS-CoV-2 type, not the more recent types like the Delta variant.
How Multiple Epitopes Should Prevent Viruses from Achieve Immune Escape
Imagine you’re a virus (actually a population of viruses), and you’re happily evolving toward an adaptive fitness peak. The close you get to the peak, the faster you evolve - runaway selection against viruses that are different from you die off due to the nasty neutralizing antibodies from a spike-protein-only antigen vaccine.
You can see the adaptive peak. Soon, you’ll be surrounding by viruses just like you, all capable of infecting every person you run into, vaccinated or not.
You’re just about there… but then you hit a roadblock. Your types start dying off. Other types are increasing, but they, too don’t seem to be able to get to the top of the fitness peak. What’s going on?
On your march to the peak, other neutralizing antibodies attack you, keeping you from taking the hill.
You and those like you cannot surpass the immunity escape threshold.
The population in which you and your kind are circulating have already had SARS-CoV-2 infections, and they have multiple B- and T-cell epitopes that keep you from surpassing the immune escape threshold.
This is reality, not fantasy.
In a study of immune response to other epitopes across the SARS-CoV-2 proteome, researchers found strong humoral responses to many epitopes SARS-CoV-2 proteins, notable strong in M, S and N proteins as well ORF3 protein (See: “The landscape of antibody binding in SARS-CoV-2 infection”. The paper is a good read, solid data, and has citations from 2004 and 2006 on synergistic immunogenicity from epitopes found among various proteins in SARS.
From an evolutionary standpoint, durable immunity to SARS-CoV-2 is expected to be more resilient and far, far more effective - and last decade - when dozens of types of memory B- and T-cells have been generated, preventing the emergence of types that can surpass the immune escape threshold. Multifactorial approaches to control viremia are also available - and will help reduce viremia in every patient, instead of forcing them to sit at home and incubate new variants (See: Who Are the World's Leading Authorities in COVID-19 Treatments?)
Thank you, Dr. Wright.
James Lyons-Weiler, PhD
