Thread by @stephanielangel

I'm excited to share with you our recent @biorxivpreprint where we demonstrate that @vaxart mucosal Ad5 #SARSCoV2 vaccines not only protected against disease but also reduced transmission after post-#vaccination #SARSCoV2 infection in a hamster model. biorxiv.org/content/10.110… A🧵/

If you follow me, you are well aware of my obsession w/ #mucosalimmunity.😂Protection generated at mucosal surfaces is at the crux of one of the biggest questions we need to answer during this unique phase of the #pandemic - How do we decrease #SARSCoV2 #transmission to others.

Considering most of the world is unimmunized (including most kids <12), the possibility that a vaccinated individual with a post-vaccination infection (aka #breakthrough) can spread #SARSCoV2 is a public health risk. We need #transmissionblocking strategies.

Vaccine strategies that induce mucosal IgA and IgG antibodies that can bind #SARSCoV2 at the site of replication (in the upper resp tract) is ideal. That is where @Vaxart comes in. We used their Ad5 vaccination technology to test oral and intranasal vaccine routes in hamsters.

We first demonstrated that oral and intranasal r-Ad-spike vaccination induced robust systemic and #mucosal anti-spike antibodies in our hamsters. After #SARSCoV2 infection, this resulted in greater viral clearance and significantly reduced disease compared to unvacc hamsters.

But we also wanted to ask: (1) Can we induce a postvaccination infection in our vaccinated hamsters & (2) does mucosal vaccination reduce #SARSCoV2 transmission to *unvaccinated, uninfected* hamsters. For this, we needed @LovelaceBio to make us a very special transmission chamber

Look how cool this transmission chamber is & look how cute my hamster schematics are😍. I'm going to leave you hanging here bc the downside of @biorxivpreprint being quick to get our preprint up is I did not have my tweets prepared & now I need to go pick up my kid. More soon!

Ok back to the very cool #SARSCoV2 transmission chamber. Basically, chamber 1 (left) houses the vaccinated, SARSCoV2 infected hamsters while chamber 2 (rt) holds the unvacc, uninfected hamsters. They can't touch so the only way the naive hamsters get infected is through #aerosols

We did some preliminary experiments to determine that all naive animals (rt chamber) get infected via #aerosols at a 1:4 (vaccinated:naive) hamster ratio. Next was to induce a postvaccination infection (aka #breakthrough) by using a high dose of #SARSCoV2.

Vaccinated hamsters were #SARSCoV2 infected and after 24 hours were introduced to their naive hamster friends in the aerosol #transmission chamber. Hamsters hung out in the chamber (at the 1:4 ratio) for 8 hrs before each hamster went back to their *own* cage (this is impt).

Next, we looked at #SARSCoV2 infection+disease in naive/exposed hamsters. Naive hamsters exposed to oral and intranasal r-Ad-S vaccinated hamsters had less viral RNA in nose post exposure and less lung inflammation/pathology compared to ctrls, which was not true for IM hamsters.

What was interesting is we saw these differences even tho vaccinated, infected hamsters had high levels of viral RNA & infectious virus at the time of housing in #aerosol chamber. We hypothesize that the higher antibodies in the nose/lung of mucosally vacc hamsters resulted in..

binding up of #SARSCoV2. So either less virus was being transmitted via aerosol (bc it was bound up to mucosal antibodies) *or* #mucosal #antibody-bound virus is transmitted via aerosols but can't bind ACE2, decreasing replication in naive hamsters.

We think these results are significant. Decreasing the amt of #SARSCoV2 transmitted to naive, unvacc individuals has a ripple effect. It decreases the risk of the exposed individual having symptomatic disease/spreading it themselves - stopping the train of #transmission.

I am a big fan of scalable, easily-deliverable, shelf-stable strategies for #globalvaccineaccess. Vaxart's #oralvaccine platform allows for this. I do not get paid in any way by Vaxart but I do believe that a tablet vaccine could help the massive #vaccineinequity around the world

Of course, there are impt things to consider for implementation of #oralvaccines, particularly in low and middle income countries. @thehandiestlab talked about this with us on the most recent #Immune podcast. Enteropathies could impact efficacy microbe.tv/immune/immune-…

Back to the paper, bc of time and $$ we weren't able to try different virus inoculum doses (likely a lower dose = less transmission) and we didn't use delta or other variants of concern. All interesting future work for sure.

As always, happy to take feedback on our paper. To our knowledge this is the first time to show that #mucosalvaccines can decrease postvaccination #transmission of #SARSCoV2 to naive hamsters. Also, first time to show hamster IgA spike-specific antibodies (bravo @drsusanjoh!)

A big thank you to my wicked smart co-author @drsusanjoh for her collaboration on this work! Really a great experience. Also to my awesome postdoc PI @SalliePermar and super talented colleague @MariaBlasi6 for helping me navigate my first big kid grant. #teamworkmakesthedreamwork