Thread by @MaxKennerly

This is hardly a model of clarity—SARS-CoV-2 antibodies are potent and vanishing? Vaccines have boosted prospects and reduced hopes?—so let's look at the studies themselves.

Short story: generally good news for a vaccine, generally bad news for herd immunity. /1

Do we usually retain immunity to coronaviruses? Researchers who have collected blood samples since 1985 took a look at 10 subjects and concluded immunity lasts likely just 6 to 12 months. Perhaps this is why there's no herd immunity for common colds. /2 medrxiv.org/content/10.110…

That said, when it came to the original SARS-CoV (2002–2004), the antibodies persisted much longer—84% still had neutralizing antibodies 36 months later. But, like the authors ominously warned in 2007, we don't know what that means. /3 nejm.org/doi/full/10.10…

So is SARS-CoV-2 like seasonal coronaviruses or SARS-CoV? A bit of both. Asymptomatic patients lose antibodies rapidly (40% are IgG negative after 8 weeks). Symptomatic patients also lose them, but not as quickly. /4 nature.com/articles/s4159…

Patients with severe symptoms have a larger antibody response than those with moderate symptoms, but they still generally lose the antibodies, like with seasonal coronaviruses. /5 medrxiv.org/content/10.110…

To be clear, this data is messy, with huge variability among patients. And nobody will say "if you don't have this many IgG or this much neutralizing titer, you're not immune!" But this data is not going the way we'd want to assure us that infection creates lasting immunity. /6

In other words, Rand Paul, who said on March 22 he had tested positive and who was apparently asymptomatic, might have already fallen to an undetectable level of neutralizing antibodies by the time he was berating Dr. Fauci 101 days later. Not good for herd immunity. /7

But there is good news. As background, here's how SARS-CoV-2 uses your cells to replicate. The antibodies made most quickly by your immune system attack the virus's nucleocapsid protein, but the most potent ones attack the spike protein or its receptor binding domain. /8

Those S & RBD antibody levels also generally decline, but some are both potent and made by everybody. If that's right, a vaccine can focus on building up more of those particular antibodies, rather provoking a generalized response and hoping it works. /9 nature.com/articles/s4158…

Anywho, immunology is a wee bit more complicated than 10 tweets by a fool like me. And I haven't mentioned T cells, partly because that's still a big unknown. I'd just rather not see a pile of conflicting headlines about antibodies saying we're both saved and/or doomed.
/end

This Moderna study is promising, but it's still just a proof-of-concept (phase 1) for mRNA vaccines, not robust data. Tiny sample sizes. The PsVNA neutralization drop-off around 6-7 weeks or so is disconcerting, and I'm not keen on the partial PRNT data. nejm.org/doi/full/10.10…