Thread by @michaelzlin

New CDC studies have good news for the boosted, I mean up-to-date, bad news for double-jabbed only

The good news: Protection from Omicron ER visits is 82% for the up-to-date

The bad news: Protection down to measly 38% for non-boosted 6mo after dose 2

cdc.gov/mmwr/volumes/7…

First a quick detour: We're now calling people who are adhering to the most recent recommendation up-to-date on their shots. I think this is a good thing. Unlike "fully vaxxed" it is language that can be continually used even as guidance changes.
usnews.com/news/health-ne…

Now back to the studies. The first one, linked in the top post, looked at ER/urgent-care visits, and at hospitalizations. Hospitalization protection against Omicron is also poor after two doses and waning. It's also restored to excellent levels by a third dose.

It's a bit confusing, but the "recentness" of the vaccine seems to matter more for hospitalization (recent dose 2 almost as good as recent dose 3) whereas the "number" of the dose matters more for ER/urgent-care visits.

We've seen that the dose number matters a lot for the creation of Omicron-reactive nAbs, which are required to prevent early symptoms, so it's not surprising that a fresh 2nd dose is not as good as a fresh 3rd dose on ER/urgent-care visits.

https://twitter.com/michaelzlin/status/1470798236919025665

It's a bit more mysterious why a fresh 2nd dose prevents 81% of hospitalizations, but a waned 2nd dose only prevents 57%. It means whatever is doing the protection initially is waned later. It could be existing Omicron-reactive nAbs (even if minor), T cells, or memory B cells.

Another CDC study from Friday looked at Omicron cases by vax status. The effect of the 3rd dose vs 2 doses is hard to say, considering all the triple-dosed had a recent shot while some of the double-dosed did not.
cdc.gov/mmwr/volumes/7…

Nevertheless it looks like the 3rd dose is protecting against being infected by 75% vs unvaxxed. This is in line with initial reports from Pfizer. It also makes sense that the VE gets better for more severe levels of disease, i.e. hosp > ER visits > infection.

So overall confirms big benefits of the third shot in terms of avoiding the ER or urgent care, i.e. serious disease, and of fresh vaccines for avoiding hospitalization, i.e. severe disease.

Now I'll wade into somewhat more controversial waters and discuss the other interesting study this week, which found Wuhan strain infection protected against being a Delta case better than vaccination (also Wuhan strain) did.
cdc.gov/mmwr/volumes/7…

That's clearly not an ideal result. We'd of course want our vaccines to be as protective as the viral infection, if possible. So what does it mean?

The endpoint being assessed, protection against Delta, requires mucosal antibodies produced against original SARSCoV2 to be broad and high enough during Delta exposure to prevent the infection. That the vaccines did worse suggests their antibodies are less broad or wane faster.

We know from the @BalazsLab study mentioned above, and linked below, that viral infection isn't better than vaccines in broadening an antibody repertoire, so I don't think it's that. So rather it seems that mucosal immunity after 2 vax shots decays faster.
sciencedirect.com/science/articl…

I mention mucosal antibodies prevent infection. Typically IgA is considered to be mucosal but recent data show IgG is there too. 9 months after infection, nasal mucous still contains high levels of IgA and IgG. We need to know if vax do the same.

nature.com/articles/s4146…

However if you look at antibody plasma levels, one study does suggest antibodies after 2-shot vaccination wane a bit faster than those after viral infection. Whether antibody persistence is any better after a third vaccine shot is now the big question.
pubmed.ncbi.nlm.nih.gov/34462761/

If dose 3 doesn't help — we'll know in a few more months — then we either need to develop better vax, or we'll have to boost every 6mo instead of 12mo (impractical), or we'll have to resign to a high level of endemicity until everyone has been infected (worrisome for the elderly)

So where can a better vaccine come from?

Here's an idea: The J&J vax may be a good intranasal vaccine!

I've been the first to say J&J is not as good as RNA vax *intramuscular*. BUT it's in adenovirus — which naturally infects the nose.

J&J: You can thank me later, if it works.

BTW the unvaxxed groups in the papers above are expected to have some people with prior infection too (maybe 30% by December). If compared to unvaxxed uninfected alone, vaccine protection would be higher in all vaccine groups.

Turns out Israel has had enough people months out from their third dose to know that antibody levels again drop after a few months. cidrap.umn.edu/news-perspecti…

They are now recommending the 4th dose for everyone 5mo out from their 3rd dose. This doesn't apply to most people in the US yet.

It's really not a viable path to be boosting everyone every 5mo. We need better vaccines.

timesofisrael.com/health-ministr…