Pfizer also has data on experienced vs. naive, but for them the LP.8.1 vaccine generally outperforms the KP.2 vaccine independent of naive vs. experienced. Interestingly, in naive mice, 2 doses of LP.8.1 also give better neutralization of KP.2 than 2 doses of KP.2. www.fda.gov/media/186597...
Blah. Meant to say, I really hope for LP.8.1 Was hoping for more options (like NB or XFG), but I get why this year, the risk:benefit ratio of being cutting edge didn’t seem worth it to the manufacturers It’s weird to go from “man I hope they select NB/XFG and not LP” to “pls update from KP.2”
NB and XFG aren't really on the table. Really the options that are feasible are KP.2, JN.1, and LP.8.1. In this particular case, they are so close together antigenically that the differences are not that important, but given the totality of evidence I would go with LP.8.1
Obviously, I wish I could pick from a dropdown menu and DIY it lol Data from pan studies showed how it’s probably best to vax with distant versions — to get naive B cells and ideally breadth as a result Idk. I’m way too deep in this stuff. I wish I could get my nasal vaccine and move on
I agree. However, I usually find myself going back to the “well, if there’s such little difference, then how did these variants manage to dominate to the degree they did” Obv more than S matters, but tbh it just makes me think those extra few mutations might really matter going forward
mutations outside S matter, but a big part of it is still timing. As antibodies contract, people again become susceptible to infection and that could catapult whatever variant happens to be around to dominate even if it has minimal evolutionary advantage over the others
You know what, you’re definitely right. I think it’s harder to tell myself that and believe it vs hearing it directly from a trusted authority on the subject (you) Maybe I should put deference on the studies that compare the variants? Idk. Industry sponsoring usually adds to my lack of finality
The 3 company’s presentations remind me of last years — where I was left feeling like Pfizer’s data was the best (collected, presented, and summary efficacy) And freaking praying they’d choose KP.2. Was so annoyed initially. V glad they ended up doing the right thing and allowing KP.2
Then we have Novavax's data. For their mice which got a JN.1 vaccine primary series, it's hard to see much difference between JN.1, KP.3.1.1, and LP.8.1. The undetectable neutralization of KP.2 despite high titers against JN.1 seems implausible for primary series. www.fda.gov/media/186596...
Is ND, No data or not detected?
I'm not positive because they don't say but I'm pretty sure it's not detected. Can't think of a reason they wouldn't have data for KP.2 here.
They just said it's "Not Determined" "Mice have a limited amount of sera... so we only evaluate the most recent and relevant variants"
Thank you- that makes more sense. I paused to wait out the public comment period
These differences in the vaccine-experienced mice are probably due to differences in their primary series before the updated vaccine booster. With Pfizer and Moderna, I would lean towards LP.8.1 because of the superiority among naive mice. Novavax's data are... weird.
For a non scientist but science interested person— can you translate this into everyday speak?
The manufacturers tested vaccines based on the spike proteins of a bunch of circulating variants to see which ones gave the best responses in mice. The mice either had no prior COVID-19 vaccines or were given a series of COVID-19 vaccines to try to model the effect of pre-existing immunity.
Based on their data, all of the variants tested did improve immune responses to the variants currently circulating by a meaningful amount. There is some variation in comparing the responses to specific variants within the same group of mice, but this could be because of differences in how...
the mice were initially vaccinated against COVID-19 (e.g., Moderna did the bivalent, then XBB1.5, and then the updated vaccine; Pfizer did 2 ancestral, the bivalent, and then the updated vaccine). All the options look good. The LP.8.1 variant is the one that is currently dominant and...
in most of the data looks very similar to KP.2 and JN.1 vaccines, though there is a slight advantage. That means that we potentially do not need to update the vaccines we already have, unless the FDA decides to recommend that we use an LP.8.1 vaccine. The manufacturers have indicated...
that they all should be ready to go with an LP.8.1 vaccine for the summer if that is what ends up being chosen.
Thank you! What was weird about the Novavax data?
The KP.2 variant and the JN.1 variant are very similar, and in their data they showed no evidence of an antibody response against KP.2 despite a solid one against JN.1. These differ from one another very minimally so the result didn't make sense. They labeled it "ND" on their slides...
Update (h/t @scoobyshakespeare.bsky.social)- The NDs here are "not determined," not "not detected," because the mice have limited serum so you can only do so many neutralization assays.
Wow. Maybe they should’ve found a different abbreviation than ND for these lool I obviously skimmed the 3 presentations so I didn’t closely examine, but I immediately thought “not detected” — which made all the data seem strange. Appreciate you covering this!
They updated their presentation to clarify what ND means but the updated version was not published on the VRBPAC meeting site