so i've been asked if it's likely that Ab waning is as likely after a third dose as it is after 2 & while it's suggestive that the answer actually is *no* (
https://twitter.com/andrew_croxford/status/1433088884620120072) i also really think we're really over-focusing on the importance of this issue.
for starters, we're also dealing w/an antigenically drifted virus. it's not a huge case of nAb epitope escape, but L452R (& T478K too, to some extent) *do* affect binding somewhat. "waning" & the rise of Delta coincide, making it hard to tease apart how much each effect...
...contributes to a vax breakthru case. furthermore, B.1.617.2/Delta is very fast & replicates to a high titer very quickly, making relying solely on a memory response tricky if your goal is preventing infection or specially transient swab positivity.
(that being said it still holds up quite nicely for severe disease, & i am fairly confident in saying that it always will).
the importance of all of these effects is *really* hard to separate. it's possible a more antigenically-drifted virus that's otherwise 3-down in RBD orientation might be *less* good at causing breakthrus b/c it enters cells more slowly, for instance.
finally, there's the question of just how important mucosal immunity is. obviously for preventing lung pathology, it's dispensable (plenty of both IgG & time to respond when you're considering LRT). would it help in nose? most likely.
now, would it decrease forward transmission likelyhood in vax breakthru cases? that's a much more complicated question to answer. intuitively i'd say yes, but am not at all confident to the effect size.
lastly, this all is massively amplified by there just being so much Delta to go around.
basically, my point is that the prevalence of vax breakthrus with B.1.617.2/Delta likely has an extremely complicated set of causes, which have been very inadequately teased apart (yes, i understand this is *very difficult*) & ...
that it's possible that in the future hypothetical nAb waning may not even matter at all. or it may only matter in the face of concurrent antigenic drift. or it may matter somewhat but added mucosal immunity from an infection or future vaccines may cancel that effect out.
idk.
idk.
this is all *really complicated* & i don't think some people are adequately acknowledging this (in their defense, all of the immunologists seem to be much more reserved than anyone else in this regard, unsurprisingly).
severe disease efficacy, however, should always hold.
severe disease efficacy, however, should always hold.
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