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* () 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.

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.

• • •

Missing some Tweet in this thread? You can try to force a refresh

Keep Current with Jasnah Kholin - 8964 - ACAB - 💉💉

Jasnah Kholin - 8964 - ACAB - 💉💉 Profile picture

Stay in touch and get notified when new unrolls are available from this author!

Read all threads

This Thread may be Removed Anytime!


Twitter may remove this content at anytime! Save it as PDF for later use!

Try unrolling a thread yourself!

how to unroll video
  1. Follow @ThreadReaderApp to mention us!

  2. From a Twitter thread mention us with a keyword "unroll"
@threadreaderapp unroll

Practice here first or read more on our help page!

More from @wanderer_jasnah

13 Sep
going to assume this is about Jeremy Farrar's recent comment to the effect of having to expect another 30k dead/year in the UK from #COVID19... in which case, this won't be the case for much longer b/c this virus will run out of immunologically naïve hosts soon.
like hot take i actually agree with Ellie *if* this were a scenario we were talking about as likely (i genuinely think we tolerate too many flu deaths, for instance), but it's just not.

can we all seriously relax a bit instead of yelling at each other over hypotheticals?
also like, society is complicated & many pandemic restrictions *do* have externalities, often ones that can be hard to see. for instance, indoor dining restrictions in HK led to a massive increase in street sleeping. travel restrictions have caused hell for refugee applicants.
Read 4 tweets
16 Aug
the paper in question, by Tom Gallagher, is finally out:…

i've read a lot of #SARSCoV2 papers this year. i've even read a lot of *good* #SARSCoV2 papers this year. this is hands-down the best one i've read this year (yes even w/4.5 months left this year).
it was the subject of his @NIDO20201 talk, which due to technical difficulties had to be uploaded later, & so i never did a livetweet. so having read the paper extensively, i'll do a summary of it & some implications.
first, a bit of background: viral fusion proteins exhibit various metastable points along a tradeoff between fusion protein stability & fusogenicity.

a highly fusogenic protein will be excellent at cell entry but be highly unstable in even slightly harsh conditions.
Read 27 tweets
26 Jul
i think a lot of people are misunderstanding the mechanism behind "shift to endemicity" in a CoV.

it's not at all due to the *virus*. yes, endemic HCoVs have certain mutations (such as a preference for closed RBDs on Spike where the CTD is the RBD) but those are from...
...selection pressure *once in the endemic state*.

what causes the shift is the virus going from antigenically novel to us having prior immunity. @dylanhmorris wrote a great article on this that is *highly* worth a read:…
but to expand a bit: once we have immunity to a virus, generally* the virus stops being able to cause *disease*. in some cases, immunity is more-or-less sterilizing, i.e. you *generally* don't get symptomatic disease.

*yes i know about Dengue. ADE has not been observed here.
Read 11 tweets
17 Jul
i was prepared for some potential bad takes when i opened… but last 2 paragraphs just blew me the fuck away.

let's start with, uh, how little empathy do you have to have to write the words "more death, although seriously concerning, is a minor problem..."?
anyway i seriously am blown away that this person is a virologist. i thought that we moved past the whole "partial immunity" nonsense an eternity ago.

you can select for escape mutants towards a monoclonal or an antiviral. b/c those can't fucking ADAPT to the virus.
guess what our adaptive immune system can do, OTOH? this is assuming it manages to escape a complex polyclonal response over multiple arms of the adaptive immune system.
Read 8 tweets
14 Jun
okay, here's the Framatome report from EDF:

"EDF a été informée de l’augmentation de la concentration de certains gaz rares dans le circuit primaire du réacteur n°1 de la centrale nucléaire de Taishan."
-> "EDF has been informed of the increase in the concentration of certain rare gases in the primary circuit of reactor no.1 of the Taishan nuclear power plant"
"La présence de certains gaz rares dans le circuit primaire est un phénomène connu, étudié et prévu par les procédures d’exploitation des réacteurs." -> "The presence of certain rare gases in the primary circuit is a known phenomenon in the operating procedures of the reactors."
Read 4 tweets
14 Jun
disclaimer: i know i'm not the target of this question (1) i'm as anti-CCP as it gets, 2) i am on record as saying i will happily DRINK a glass of the undiluted Fukushima wastewater & i stand by that), but let's take a look at the Framatome/Areva report.
i haven't been able to find the actual report they gave the US DoE, so right now i'm going by… &… under the assumption that news agencies didn't fuck up interpreting the science.
(if anyone can find a copy of the official statement from Framatome i'd really like to read it. English or French is fine).
Read 20 tweets

Did Thread Reader help you today?

Support us! We are indie developers!

This site is made by just two indie developers on a laptop doing marketing, support and development! Read more about the story.

Become a Premium Member ($3/month or $30/year) and get exclusive features!

Become Premium

Too expensive? Make a small donation by buying us coffee ($5) or help with server cost ($10)

Donate via Paypal Become our Patreon

Thank you for your support!

Follow Us on Twitter!