Will Omicron Save Us from Vaccine Induced ADE?
Evidence published in April 2021 shows that the chance for vaccine immunity was lost with the Beta variant. Plus some bad and good news about Delta and Omicron from realm of viral evolutionaryomics.
UPDATE: My speculation that Pfizer did not include the ADE motif was incorrect, based on the analysis of the wrong open reading frame. After reading this, see my article on this update.
There is a fascinating thread in academic publishing on the origin and emergence of SARS-CoV-2 variants. I have an in-depth article coming out here on Popular Rationalism soon reviewing the work of a French team that I have to say is very impressive. But to the point of today’s article:
Evidently, the Delta variant is part of the trunk of the tree of variants that includes, among others, a variant in a specific epitope in the spike protein associated with disease enhancement. That variant, D614G, is found in the epitope amino acids 597 to 603, LYQDVNC, in SARS-CoV-1. and is found in 611-617 in the spike protein of SARS-CoV-2.
People in Asia exposed to SARS-CoV-1 can still mount neutralizing antibodies against LYQDVNC.
As part of my research for my next article, I came across this stunning comment in a study published in April 2021 in the journal Cell by scientists at Massachusetts General Hospital, Brigham and Women's Hospital, MIT, Harvard, and elsewhere:
“Finally, we found that B.1.351 variants exhibited remarkable resistance to neutralization, largely due to three mutations in RBD but with measurable contribution from non-RBD mutations. The magnitude of the effect is such that B.1.351 strains escaped neutralizing vaccine responses as effectively as distantly related coronaviruses.”
B.1.351 is the beta strain. That’s the one after Alpha, which is the one after the Wuhan strain. Beta was first identified in late 2020; mass vaccination started (in the US) in Dec 2020. The makings of vaccine escape were already in place before mass vaccination began. This is why you don’t start mass vaccination at the height of an outbreak, epidemic or pandemic: you’ll select for variants that escape the vaccine. That’s vaccine selection, and should be part of Vaccinology 101.
I have traced the variation tracked in the scientific literature and all of the post-Wuhan named variants have variation that confers vaccine escape. ALL of them.
Part of the genetic variation that confers upon the SARS-CoV-2 virus the ability to escape the vaccine was present in sequences in Wuhan, in January, 2020.
In April, 2021 we knew there were variants that had escaped the vaccines sufficiently to make the available vaccines no better against SARS-CoV-2 than “distantly related coronaviruses”.
The bad news is that the changes in LYQDVNC (starting with Beta) appear to be related to disease enhancement - specifically, antibody dependent disease enhancement, from Beta to Delta, this motif is appears to biochemically allow easier opening of the spike protein, and changes the biochemistry of the attraction of the spike to the ACE2 receptor (all findings due to leviathan efforts of a French team led by Jacques Fantini).
The good news is that the academic field of molecular evolutionary virology is all over this - they are not likely to forget their own studies. My next article goes into great detail on the findings by Fantini and colleagues- they notice they difference in LYQDVNC tracing back to Beta. If what that team is saying is correct, and there is no reason to believe it is not, then some people who vaccinated early are at increased risk of high viremia during their inevitable infection if it’s Delta.
The good news is that the LYQDVNC ADE-associated epitope is highly altered in Omicron (from another preprint from Fantini’s team):
“Surprisingly, the recently emerging omicron variant does not seem to follow this general rule as its ADE epitope is heavily affected by a combination of single point mutations (A67V, L212I), two deletions ((∆H69, ∆N211), and a 3- amino acid insertion (between R214 and D-215)”
My next article focuses on the fact that some of the elements of disease enhancement have been with us since January, 2020 as well - in fact, the fact that LYQDVNC was in SARS-CoV-1 caused vaccine researchers at the time to call for exclusion of this epitope from SARS-CoV-1 vaccines.
LYQDVNC is present in the Moderna spike protein, 100% match
LYQDVNC is absent from the Pfizer mRNA encoded spike protein (Stanford sequence).
One wonders if Pfizer purposely modified their mRNA to avoid unsafe epitopes.
If anyone has any links with evidence on whether Pfizer heeded warnings on ADE and pathogenic priming, please drop them in the comments below.
In the meantime, it’s important for people who think they are immune to realize that they may well be at risk. We need to find out if those who have been infected to then vaccinate alter their immune focus toward LYQDVNC.
And anti-antibody therapies against antibodies against LYQDVNC may prove essential to preventing ADE.
Also, in the meantime, I think it’s time we start hoping that Omicron replaces Delta and that Delta does not persist much longer. Delta is going to continue to take out people who are vaccinated and unvaccinated on its way out. It’s a bad variant capable of killing the vaccinated and the unvaccinated, including the vaccinated and those with antibodies to LYQDVNC.
Nevertheless, my friend and colleague, a man to whom we all should send a ton of love, Dr. Pierre Kory is sad, but hopeful:
As an evolutionary biologist, I can say that our greatest fear right now is the establishment of a dynamic equilibrium between LYQDVNC and non-LYQDVNC SARS-CoV-2. Given the rapid evolution of mRNA viruses, it seems highly unlikely, but that would lead in a DNA virus to fluctuating high-death and low-death seasons. This is idle speculation at this point.
But if we are to have vaccines, they should not induce antibodies to LYQDVNC. Such antibodies are likely to cause ADE. They should not encode the spike, either - the myocarditis data shows us why. COVID-19 vaccines - all vaccines - should also not induce antibodies against unsafe epitopes that will lead to autoimmunity.
What’s your opinion? Do you agree or disagree? Drop your thoughts in the comments. And hold on for the next article… it is very detailed, it is all about Fantini et al’s fascinating work, and is sure to get you thinking.
Omicron might yet prove the `vaccine` that (nearly) none of us can avoid, but one which helps provoke a healthy immune response and does so with far less risk than the Pfizer or Moderna mRNA vaccines. Time will shortly tell.
Q - will prophylaxis like quercetin to get zinc into cells, D, C and others help? and I value your work and would appreciate it if in your next major, detailed article you include language explaining to people without advanced degrees in biology. I am inclined to take your course.