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
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
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
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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