Thread by @rishirajgoel

Our paper on antibody & memory B cell responses to SARS-CoV-2 #mRNA vaccines is out @SciImmunology

- 1 vs. 2 doses?
- What about age & side effects?
- Relationships btw/ antibody & memory cells?

We look at all that & more... full #Tweetorial below 💉🧵

immunology.sciencemag.org/content/6/58/e…

As others (including @florian_krammer @Daltmann10 etc) have shown, folks who have recovered from COVID only need 1 dose to get peak antibody responses to full-length spike protein and the RBD. People who are SARS-CoV-2 naive need 2 doses for optimal responses

Similar data for neutralizing ability against wild-type (D614G) strain & the B.1.351 (S African) variant

2nd dose especially important in people w/o prev infx... 50/50 on neutralizing antibody against D614G & very little against B.1.351 after dose 1. Great response after dose 2

We also looked at memory B cells using a strategy inspired by @profshanecrotty @TheBcellArtist

mRNA vax induced robust memory B cell responses to full-length spike & RBD

1 dose = peak response in recovered folks. Continued improvement w/ 2nd dose in the SARS-CoV-2 naive group

In SARS-CoV-2 naive individuals, these memory cells continue to improve over time. Increase in % of IgG+ cells and also a focusing of the response on the RBD

Recovered individuals again get little qualitative benefit to their B cell response from 2nd dose

Another question we get a lot: how does age affect vaccine response?

There is a slight negative trend btw/ age and antibodies

We do see a stronger association btw/ age and memory B cells post-boost, but everyone is still over baseline so something to keep an eye on longer-term

What about side effects? Turns out you do get some benefit to your antibody response if you had systemic symptoms (i.e fever, chills). No pain, no gain...

But side effects do not impact the generation of memory cells. And even w/o side effects, everybody had a great response

Relationships btw these different measures of immunity: do antibodies predict memory (or vice versa)?

Turns out that just measuring post-boost antibodies doesn't tell us much about memory. BUT baseline memory does predict antibody recall upon re-exposure in recovered folks

So what are the take-home points:

1) Probably ok to delay or skip 2nd dose in individuals who previously had COVID

2) 2nd dose important for the quality of immune response in previously uninfected individuals

3) Some association of age & side-effects w/ vaccine response

Check out the full paper for more analysis: immunology.sciencemag.org/content/6/58/e…

Massive thanks to the whole @Penn_IFI @PennMedicine team led by @EJohnWherry @SCOTTeHENSLEY & co, as well as co-first authors @s_apostolidis @markmpainter @divijmathew. Nobody does team science better than @Penn