How long does immune memory last after #mRNA vax?
Immunity vs. variants?
What happens when you “boost” w/ vaccine?
Our work on durability & evolution of memory responses to SARS-CoV-2 vaccines: biorxiv.org/content/10.110…. Antibodies, memory B/T cells, & more. Full thread below 💉👨🔬
Lots of data here so I’ll only focus on the highlights. TLDR: immune memory looks great and improves over time (even against variants). Boosting existing immunity w/ vaccine significantly increases antibody in the short-term but w/o much effect on already durable memory B/T cells
Antibodies - 2 dose mRNA induces high antibodies/neutralization. Even higher for “hybrid” immunity in folks w/ prior infection + vax. Antibodies do come down over time (THIS IS EXPECTED AND TOTALLY NORMAL FOR AN IMMUNE RESPONSE)
Memory B cells - also efficiently generated by 2 doses of mRNA. But unlike antibodies, these actually continue to INCREASE over time. And when you re-activate these memory B cells, they can rapidly respond to produce more antibodies that can bind/inhibit SARS-CoV-2
We also looked at memory B cells against different variants and compared w/ natural infection. Turns out the majority of memory B cells induced by mRNA vax can bind Alpha, Beta, AND Delta… mRNA vax also slightly better against variants than mild COVID-19 (panels E/F)
These variant binding memory B cells evolve from variant non-binders through somatic hypermutation in immune structures called germinal centers (GCs). Amazing work from @TheBcellArtist shows that GCs persist for months after vax. See full text for our sequencing data on this
What about T cell responses? CD4+ T cells strongly induced after 2 mRNA vax doses w/ slight contraction from peak (again, expected for a normal immune response), then very stable from 3-6 months. CD8s also strong after 2 doses w/ a bit more variability at memory timepoints
With all this data we could construct an “immune landscape” of mRNA vaccination. Note how all the 6-month samples cluster away from pre-immune baseline samples! Suggests that mRNA vax generates durable, multi-component immune memory to SARS-CoV-2
Some cool human immunology findings led by @markmpainter - antibody levels at later time points are highly correlated w/ early CD4+ T cell responses, suggesting that these cells are essential for coordinating the long-term immune response
Finally, mRNA vax in folks w/ prior immunity from COVID allowed us to study what “boosted” responses might look like… Boosting here increased antibodies likely through recall from memory B cells. But decay rates over time are similar & no long-term benefit to cellular immunity
To recap - immune memory vs. SARS-CoV-2 (including variants) looks durable for at least 6 months after mRNA vax. Memory cells do the heavy lifting when antibodies start to go down - this may explain the increase in "breakthrough" infections but good efficacy vs. severe disease
Boosting is more complicated. Antibodies definitely go up, but no change in their decay rate + no long-term increase for memory B/T cells. The temporary ⬆️ in protection from antibodies may work on an individual level, but unclear if we can just boost our way out of this pandemic
Our work on B cell memory to Omicron + other variants is now online @CellCellPress
How does a 3rd shot of original mRNA vax work vs. variants? Does it increase the durability/quality of immune responses? What happens after a second boost? Key findings 👇
How does original mRNA vax work for Omicron + other variants? Does a 3rd shot increase the durability and/or quality of immune response? What factors predict boosting, and what happens after a second boost?
We previously studied immune memory for 6 months after mRNA vax. In this study, we followed the same individuals out to ~9 months after primary 2-dose vaccination, as well as ~3 months after a 3rd (booster) dose
Remember the headlines about 📉 antibody levels (TOTALLY NORMAL AND EXPECTED)?
Binding/neutralizing antibody levels stabilize between 6 and 9 months post-vax. A 3rd dose (or breakthrough infection) supercharges the antibody response w/ lasting benefit ~3 months post-boost
How long does immune memory last after #mRNA vax? Is it effective vs. variants? What about “boosted” responses?
Full 🧵⬇️...
Antibodies are important for protection, but our immune system can also remember viruses through memory B and T cells
We measured all components of immune memory for 6 months after #mRNA vax. Vaccination in people w/ prior immunity also let us study "boosted" responses
#1 - Antibodies:
2-dose mRNA induces high levels of antibodies (blue). Even higher in "boosted" responses (red)
Antibodies decline over time (THIS IS NORMAL AND EXPECTED). But neutralization declines more slowly than binding antibody, suggesting higher quality antibody persists
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
Our study on #mRNA vax in #SARSCoV2 naive/recovered individuals is up on medRxiv! Massive team effort btw/ @EJohnWherry lab + others @Penn_IFI to profile both antibodies & antigen-specific memory B cells following 1st/2nd doses. bit.ly/3rlfhwO. Full tweetorial below 💉🧵
1) Consistent w/ what others (e.g. @florian_krammer) have shown: COVID-experienced folks don’t have an increase in antibodies after 2nd dose… clear benefit for people who are COVID-naive
2) We also find the same pattern for antigen-specific memory B cells… COVID-experienced folks have an increase in spike+ and RBD+ memory cells after the first dose, but then plateau w/ no increase in frequency or class switching after the second dose