Jeremy Kamil Profile picture
Jun 20 13 tweets 5 min read Twitter logo Read on Twitter
Too early to say what this means for @Moderna's #CMV (cytomegalovirus) mRNA vaccine candidate, which is already in Phase III trials. However, this preprint suggests CMV's pentameric gH/gL complex is not important for transplacental infection. #StopCMV 🤰 🧵biorxiv.org/content/10.110…
CMV is notoriously difficult to vaccinate against. When he was still @pfizer, Phil Domitzer & colleagues "threw the book" at rhesus CMV --trying all leading vaccine strategies. The virus still infected, shed and transmitted horizontally just fine. 2/ academic.oup.com/jid/article/22…
Moderna has focused its mRNA vaccine on gB (the viruses' membrane fusion protein, functionally analogous to the S2 domain of a coronavirus' Spike)..and on the receptor binding gH/gL complex that's commonly referred to as "the Pentamer" because it's made up of 5 glycoproteins. 3/
There was initially much excitement about the Pentamer as a vaccine target after Antonio Lanzavecchia and colleagues showed that very tiny amounts of anti-Pentamer antibodies potently neutralized the virus from infecting epithelial cells.. 4/ pnas.org/doi/10.1073/pn…
However, that paper & basically all the other reports showing anti-Pentamer antibodies to be so potent relied upon in vitro infection models, in which the antibodies neutralized cell-free virus from infecting epithelial cell lines. What's the in vivo relevance of that? 🤷 /5
In fact, @StantonRich & co-authors found the Pentamer drives antibody-resistant cell-to-cell spread. Maybe that helps explain why it's so easy to neutralize Pentamer on cell-free virions? Maybe its 'real job' isn't to help cell-free virions enter cells? 6/ pnas.org/doi/full/10.10…
In this scenario, the Pentamer is a "sitting duck" 🦆 on cell-free virions simply because evolution has not demanded it to be "neutralization resistant." Despite the huge importance of the Pentamer for in vitro infectivity, this could make sense. 7/ journals.asm.org/doi/10.1128/JV…
Now, CMV has 2 different gH/gL complexes. The one evolution probably demanded be neutralization resistant is gH/gL/gO, aka 'Trimer." gO fits the bill for a viral entry protein that resists antibodies. >50% of its molecular weight is N-linked glycans! doi.org/10.1128/jvi.02…
Another concern about the Pentamer as a vaccine target is that studies with Rhesus CMV (RhCMV) show that the RhCMV counterparts of two human CMV Pentamer components, UL128 and UL130, counteract important (and unusual) MHC-E restricted T cell responses. 9/ science.org/doi/10.1126/sc…
In any case, Moderna's mRNA vaccine trial does not "read out" until April 2026.. so, we'll have to stay tuned before we find out whether their Pentamer + gB based #CMV vaccine proves efficacious or not. 10/ clinicaltrials.gov/ct2/show/NCT05…
Either way, it remains important to develop effective vaccines against CMV congenital infection & ways to prevent CMV disease in immune-compromised people. 11/
...CMV is a fascinating virus for learning about biology & immunology. But it's the #1 infectious cause of birth defects and is also a common cause of serious, life threatening infections in people who have received solid organ or stem cell transplants. #StopCMV
Ooops.. that'd be @moderna_tx .. (I tagged the wrong @ Moderna in the OP) 13/

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More from @macroliter

Mar 31
1/ Every person who rapidly shares viral genome sequence data should be celebrated & I'm proud to have helped @GISAID grow. I believe in the platform & its cause is noble. Most of all, I believe in the global community that is the true fabric of GISAID. But there's a problem.. 🧵
2/ The person who is in effect, CEO of GISAID, Peter Bogner, acts as judge, jury & executioner of all decisions at GISAID, has made big mistakes, including acts of overt dishonestly. His mistakes now threaten the platform's credibility all over the world. science.org/content/articl…
3/ However, it's critically important that we do not conflate Mr. Bogner with GISAID. GISAID's global data sharing community are in large part orphaned now. This is a serious threat to global health security. We still need to know about new viruses promptly ...
Read 15 tweets
Mar 29
1/ My Israeli friend once told me a Bedouin proverb that his father told him: “Lies don’t have legs…” they don’t walk on their own.. you have to remember them and there’s a weight to keeping your story straight. 🦵🏽🦵🏽
2/ GISAID is a fantastic platform built by a visionary. Hugely important for global health. Tragically, the visionary in charge doesn’t care about truth & the lies are getting too heavy to bear. I hope GISAID survives. But it’s in desperate need of reform. science.org/content/articl…
3/ Lies don’t have legs. Truth generates its own receipts.
Read 6 tweets
Mar 29
When an organization doesn’t have sufficient internal oversight to prevent bad decisions, you’ll see good feedback coming from outside. Either way, @GISAID should not be changing the terms of use in a hasty & non-transparent manner.
In this case, it looks like Peter Bogner (he alone is in charge) is going out of his way to accommodate the needs & wishes of a single data submitter: The Chinese CDC. WHY DOES HE INVENT TOTALLY NEW POLICIES FOR THE CHINESE GOVERNMENT?
Mind you, GISAID’s March 21 official statement re: @flodebarre @acritschristoph et al’s Zenodo report is a verifiably false misrepresentation of the facts. Why hasn’t Bogner apologized? What motivates him to risk so much for George Gao & the China CDC? gisaid.org/statements-cla…
Read 6 tweets
Mar 26
1/ GISAID can’t unilaterally release these data. That’d severely hurt the platform. But Peter Bogner —the “data diplomat”— is M.I.A. Why wasn’t he working the phones to broker a solution here? In 2006, he came to the rescue after Indonesia refused to share bird flu samples. 🧵
Indonesia was rightfully upset that weathy ‘Western’ countries in the “Global North” were the only ones benefitting from the influenza vaccines that pharma companies would develop. Together with Nancy Cox of
@CDCgov, Bogner launched GISAID to help resolve the impasse.. 🧵 2/ Indonesia agrees to hand bi...
Bogner was widely credited with helping broker an agreement wherein Indonesia would share flu samples again. @ggronvall & @RickABright know better, but this dispute might also connect with how @WHO’s Pandemic Influenza Preparedness framework began.. who.int/initiatives/pa… 🧵3/
Read 6 tweets
Mar 18
The mainstream media —e.g., @CNN @NBCNews— is basically just repeating a lab leak friendly narrative of ambiguity, when there is in fact very little ambiguity here at all. China is working hard (yet clumsily) to cover up that COVID-19 came from their illegal wildlife trade Image from Midjourney AI .. ht @alchemytoday
.@NBCNightlyNews dishonestly used an out-of-context clip from my interview w @stephgosk to make it seem I’m skeptical of the Raccoon dog 🧬 findings as unreliable to indicate wet market animal trade origin of COVID. This was just a caveat, not the takeaway nbcnews.com/nightly-news/v…
The good reporting as usual happens in print. Here’s a several great pieces 1. By @MaryKekatos abcnews.go.com/Health/new-rep…
Read 8 tweets

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