Manuscript Alert!! Thread. In our latest manuscript, we look at the efficacy of intranasal vaccination with the Oxford/Astrazeneca vaccine, in both hamsters and rhesus macaques: biorxiv.org/content/10.110…
We started this work since we and others see no to limited differences in nasal shedding of SARS-CoV-2 in vaccinated animals, even though lung tissue is fully protected. Of course, this is a fantastic result already, but we might still experience transmission of the virus.
Intranasal vaccinations have been used for e.g. influenza (FluMist) and elicit a mucosal response (basically an immune response where the virus is replicating, in your nose).
First, we went into hamsters. We vaccinated via intranasal or intramuscular vaccination and challenged them via the intranasal route. We only see a reduction of shedding in the group that received the intranasal vaccination (red) vs controls (green). Image
Lung tissue is protected in both groups (red and blue vs green, infectious virus): Image
Then, we looked what would happen with transmission. SARS-CoV-2 transmits very efficiently between hamsters (direct contact) with just 4 hours exposure. Again, a reduction in shedding was observed in the intranasal vaccine group (red) vs controls (green). Image
We again saw no virus in the lungs of the intranasally (red) vaccinated group, but a little bit in the group that received an intramuscular vaccination (blue). Image
Based on this data, we moved on to the rhesus macaque model. Intranasal vaccination with ChAdOx1 nCoV-19 resulted in a lot of different immune responses, I just highlight one here, IgA in nasal mucosa. Blue = vaccinated animals, Purple = control animals. Image
We also measured IgG and IgA in sera and BAL, virus neutralizing antibodies in sera, and different effector functions, such as antibody-dependent phagocytosis (see Figure 5 in the paper).
With the help of @FatimaAmanat and @florian_krammer, we were able to test the NHP sera against RBD containing the N501Y mutation, which is prevalent in some of the new variants (B.1.1.7 and B.1.351). Binding is very similar. Identical symbol = same animal. Image
Importantly, we did see a reduction in shedding as well! Here is infectious virus (not RNA!) in nasal swabs. Blue = vaccinated animals, Purple = control animals. Image
Finally, we detected minimal evidence of virus in lung tissue of vaccinated animals, in contrast to control animals. Image
The data supports the investigation of intranasal delivery of COVID-19 vaccines. With the roll-out of COVID-19 vaccines worldwide, it will be crucial to investigate whether the vaccines provide sterilizing immunity...
...or whether vaccinated people are still susceptible to infection of the URT and onward transmission of the virus.
Anyhow – very excited about the manuscript and thought I would share! Thanks for reading 😊

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More from @DrNeeltje

30 Jul 20
Our ChAdOx1 nCoV-19 vaccine study is now published in Nature! Huge thanks to all involved. #SARSCoV2 #vaccine #chadox1 nature.com/articles/s4158…
Compared to the bioRxiv publication, we have now included a prime boost group, and 3 more control animals
The efficacy is striking in the lungs - no pneumonia after a single shot, no to very limited viral RNA in BAL
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