NIAID/NIH researchers developed a replicating RNA vaccine expressing the Omicron (B.1.1.529) spike. They conducted animal studies for the following objectives:
1-How does pre-existing immunity affect the antibody response to an omicron-targeted booster vaccine (in mice) 1/
1-How does pre-existing immunity affect the antibody response to an omicron-targeted booster vaccine (in mice) 1/
In mice, their main objective was to evaluate the effect of pre-existing immunity on the antibody response to the B.1.1.529-targeted vaccine (using an influenza repRNA vaccine to control for background immunity to the repRNA backbone) 👇 2/ 
2-In hamsters, the main objective was to evaluate the protective efficacy of a single-dose B.1.1.529 repRNA vaccine relative to the ancestral A.1 repRNA vaccine following infection with B.1.1.529 virus as shown in the study design 👇 3/
In the pre-immune mouse study, they observed a pronounced negative impact of pre-existing A.1 immunity on B.1.1.529-targeted antibody responses that was independent of anti-repRNA background immunity. 4/
Only the A.1-naive mice mounted B.1.1.529-specific IgG & NAb responses after a single boost and mice that were only primed against A.1 (single dose) appeared to respond to two booster doses of the B.1.1.529 vaccine with increases in B.1.1.529 RBD IgG responses 5/
What could be the reasons behind these results?
Two reasons:
1) Some interfering role of pre-existing anti-A.1 spike antibody levels (perhaps interfering with B cell/repRNA-produced antigen interactions) or…..
6/
Two reasons:
1) Some interfering role of pre-existing anti-A.1 spike antibody levels (perhaps interfering with B cell/repRNA-produced antigen interactions) or…..
6/
2) A.1-specific memory B-cells preferentially expanding in response to B.1.1.529 antigen through cross-reactive interactions (aka antigen imprinting)
Since they did not see a boosting of the A.1 Ab responses following B.1.1.529-repRNA booster, No 1 above is more likely 7/
Since they did not see a boosting of the A.1 Ab responses following B.1.1.529-repRNA booster, No 1 above is more likely 7/
Hamster study: the objective no. 2
Finally, to see whether or not B.1.1.529-targeted immunity would offer a significant benefit over A.1-targeted immunity they looked at A.1-specific as well as B.1.1.529-specific NAb responses in the primed hamsters
8/
Finally, to see whether or not B.1.1.529-targeted immunity would offer a significant benefit over A.1-targeted immunity they looked at A.1-specific as well as B.1.1.529-specific NAb responses in the primed hamsters
8/
A.1 vaccination (single dose) did not drive NAb responses against B.1.1.529 virus & B.1.1.529 vaccination (single dose) did not drive NAb responses against A.1 virus. But each vaccine did drive NAb responses against homologous virus (as expected). 9/
Conclusions:
1-A replicating RNA vaccine expressing the B.1.1.529 spike is immunogenic in mice & hamsters
2-Pre-existing immunity may impact the efficacy of B.1.1.529- targeted boosters. 10/
1-A replicating RNA vaccine expressing the B.1.1.529 spike is immunogenic in mice & hamsters
2-Pre-existing immunity may impact the efficacy of B.1.1.529- targeted boosters. 10/
3-B.1.1.529-targeted vaccine provides superior protection compared to the ancestral A.1-targeted vaccine in hamsters challenged with the B.1.1.529 VoC after a single dose of each vaccine. 11/
Link to the study 👇
biorxiv.org/content/10.110…
Link to the study 👇
biorxiv.org/content/10.110…
Here is the link of the detailed 🧵 by @jesseerasmus 👇
https://twitter.com/jesseerasmus/status/1489286926846750720?s=21
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