Thread by @rishirajgoel

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

Full text available here if you want to read all the details: biorxiv.org/content/10.110…

Happy to discuss/share any of the data

Thanks to all the authors and collaborators. Co-first authors @markmpainter @s_apostolidis @divijmathew have done a lot of the work here w/ constant feedback/support from all of @WherryLab @Penn_IFI. And of course @EJohnWherry for his mentorship over the past 8 months