Antibody depending enhancement was a threat that looked possible (or even likely) a year ago, based on experience with historical CoV vaccine attempts. Then it started to look like a non-issue during trials and early rollout. Now it’s back on the table. First described in… 1/7
…a paper published in February, i.e. prior the emergence of Delta and only looking at Wuhan-Wuhan re-exposure. Enhancement was seen in just a small subset of macaques: cell.com/cell/fulltext/…
Then a study that used a Wuhan-Delta sequence of spike exposure found something… 2/7
…really different👇🏻 journalofinfection.com/article/S0163-…
So what does that mean, what can we expect now that the 3rd doses of Wuhan spike based vaccines are being rolled out? The Original Antigenic Sin concept tells us that repeated exposure preferentially boosts old antibodies. (More… 3/7
…about the concept of OAS in this review. The whole paper is great, but read at least the Introduction part.) perspectivesinmedicine.cshlp.org/content/11/5/a…
OK, back to the case of ADE & why I’m a bit more worried than was in February. The NTD enhancing Ab study was a single report, but already… 4/7
…cause for concern. However, confirmation is already here from Japanese scientist: “we found that the Delta variant completely escaped from anti-N-terminal domain (NTD) neutralizing antibodies, while increasing responsiveness to anti-NTD infectivity-enhancing antibodies.” 5/7
The researchers also played around with a few common RBD mutations to simulate what could happen if a future descendant acquired these: “some BNT162b2-immune sera lost neutralizing activity and enhanced the infectivity.” biorxiv.org/content/10.110… 6/7
This is bad news, because a relatively small leap is needed for the virus to not only largely evade current vaccines, but also to make the vax trigger more severe disease. In fact, some of the sequenced ‘variants’ already show the accumulation of several of those 4 mutations. 7/7
(Sorry for the typo + auto-carrot on my iPad, ADE is of course short for Antibody Dependent Enhancement. I won’t delete it now.)
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In below thread immunosuppression was identified as the likely mechanism for the observed ⬆️ risk of COVID during the 1st 14 days post first jab.
A study looking at immunological changes in yellow fever vaccination reported very similar trajectories. tandfonline.com/doi/full/10.10… 1/4
“We found that the numbers of leukocytes sharply declined 7 days after vaccination, increasing back to baseline levels after 14 days. In contrast to primary vaccination, we did not observe a decrease of cell counts after recall vaccination (10 years after primary).” 2/4
The Phase I/II trials of the Pfizer-BioNTech vaccine also showed this transient immunosuppression. Rather profound effect. nature.com/articles/s4158…
Thanks to @dockaurG for the link. 3/4
1/ I have a thread about natural immunity to SARS-CoV-2, but I was asked to do a comparison with vaccine induced immunization. Interestingly, deep analysis of the two is largely missing. A recent study will do the job, science.sciencemag.org/content/early/…
2/ but we need to focus on results, not conclusions, because even though the study was designed to compare the two types of immunization, plus added the effect of a booster jab on top of infection, the interpretation is a bit twisted to mostly compare the 2 jab scenarios.
3/ Quote:
"Three individuals who previously showed a response, despite lack of laboratory evidence for infection (therefore presumably a cross-reactive response to an endemic human coronavirus) showed an unchanged or decreased [T cell] response to spike after vaccination."
There’s a curious correlation between countries/regions of high prior SARS2 exposure and a resurgence upon the start of mass V immunization programs. I’ve been thinking a lot about this lately, and the only explanation that could fit observations is… 1/ bmj.com/content/372/bm…
reactivation of dormant viruses in the population. (Seasonal) respiratory viral dormancy has been debated a lot for decades, but there’s still no consensus on where exactly these virions could lay dormant in the body, nor on the trigger(s) & mechanism(s) responsible for… 2/
reactivation. In light of recent research, my (educated?) guess is that the small intestine, and associated immune structures, is more likely place for this to occur than the respiratory tract. Admittedly, this is speculative, but neither implausible nor could I come up with… 3/
Neurological complications of COVID-19 are the result of spike mimicry induced autoimmunity?
“these mAbs target both anti-viral and anti-neural antigens—including one mAb that reacted to both spike protein and neural tissue.” cell.com/cell-reports-m…
“Testing for antibodies to platelet factor 4 (PF4) was positive in 22 patients” out of 23.
Autoimmunity is the most likely reason for the thrombotic events, at least in connection with the Oxford/AZ adenovirus vector vaccine. nejm.org/doi/full/10.10…
“20 novel human peptides mimicked by SARS-CoV-2 have not been observed in any previous coronavirus strains (HCoV, SARS-CoV, and MERS).” nature.com/articles/s4142…
“We report that SARS-CoV-2 has evolved a unique S1/S2 cleavage site, absent in any previous coronavirus sequenced, resulting in the striking mimicry of an identical FURIN-cleavable peptide on the human epithelial sodium channel α-subunit (ENaC-α).” elifesciences.org/articles/58603