Thread by @MonicaGandhi9

NASAL VACCINES: To explain nasal vaccines, we have to explain the immune system first.
IgA is an antibody that helps attack the pathogen and exists in mucosal surfaces (like nose/mouth)
IgG is an antibody that is in the bloodstream
bbc.com/news/world-asi…

Cellular immunity is fantastic, redundant (so even if one cell line down in immunocompromised, have other), generated by either vaccine or infection; Comprised of
T cells- so in breadth from vax - works even across spike protein with its mutations

https://twitter.com/MonicaGandhi9/status/1424174473402408960

And the 2nd type of cell produced by vaccines or infection -B cell- amazing thing about B cells is that - if see omicron or one of its subvariants in future- they make antibodies adapted to that variant or subvariant (aided by T cells); adaptive immunity

https://mobile.twitter.com/monicagandhi9/status/1443016556460470272?s=10

I think everyone in the world has now noticed that COVID-19 vaccines (administered intramuscularly as a shot) are excellent at preventing severe disease (which is what T and B cells do) but do not prevent mild infections (1st saw this with delta but known fact about vaccines-

Vaccines prevent DISEASE (usually severe disease) but not all infections (for instance, measles vaccine prevents the manifestations of the disease; if we swabbed all noses, may have measles in there). Ok, traditionally vaccines administered by shot don't

traditionally raise high levels of mucosal antibodies (IgA). mRNA vaccines did raise some IgA but not reliably (62% here); infection raises IgA more reliably as virus enters through nose. Healthcare workers here protected more by infection + vax (hybrid)
nejm.org/doi/full/10.10…

So, nasal vaccines?- Used in the movie Contagion but don't actually see nasal vaccines used much because haven't reliably worked better than intramuscular vax. Nasal vax for influenza stopped '17-'18; resumed '18-'19 but no efficacy estimates yet from CDC
cdc.gov/flu/prevent/na…

But advantage of NASAL VACCCINE not only no needle (put in nose by syringe) but should raise IgA at higher levels and theoretically prevent more mild infections (your shots or natural infection already preventing severe disease). Farthest along Bharat BBV154 intranasal vaccine

Nice summary of phase 3 trial of BBV154 vaccine from Tribune India- please note this trial did not have efficacy endpoints (how well prevented infection) but safety and immunogenicity (markers of immunity). Given alone or after 2 shots of vax used in India
tribuneindia.com/news/nation/bh…

And for interest, here is trial design for the BBV154 vaccine plus the intramuscular vaccine Bharat makes (Covaxin) from Clinicaltrials.gov. Many of us like #covaxin as it is whole inactivated virus so shows body entire virus (not just spike, mutates)
clinicaltrials.gov/ct2/show/NCT05…

Okay in rats, mice, hamsters, and rhesus macaques, BBV154 does what should do- elicit nice high levels of IgA antibody (mucosal). And the phase 3 trials in humans for BBV154 (& a China-made nasal vaccine) complete but preprint not yet up or that I can see
frontiersin.org/articles/10.33…

However, the data has been presented to regulatory agencies for BBV154 (& one in China, Russia, Iran) and data looked good enough (again, for safety & immunogenicity) that products actually approved & being rolled out as in Tribune India article above
nature.com/articles/d4158…

Here is preprint of phase 3 trial of BBV154 (INCOVACC trade name) looking at mean neutralization antibody titers (IgG), secretory (mucosal)-IgA and serum-IgA responses, cell-mediated immune responses in 2998 on BBV154 vs 162 on Covaxin (whole virus vax)
papers.ssrn.com/sol3/papers.cf…

Interesting to observe that T/B cell responses were generated by both Covaxin and BBV154 (without major differences); that Covaxin generated higher IgG levels; but BBV154 generated higher serum IgA levels (but not much higher secretory IgA than Covaxin). Immunogenicity good

So safety/ immunogenicity study (nasal drops) of this Bharat vax developed with Wash U in St. Louis (others like Aztreneca nasal vax failed to produce mucosal antibody). Now need phase IV human effectiveness data to see if prevents infection well
medicine.wustl.edu/news/washus-na…