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I had the great pleasure of discussing vaccines for #SARSCoV2 #COVID19 #coronavirus on @MPRnews this morning with @KerriMPR. I was especially glad to join my colleague from @UW, Dr. Deborah Fuller, and hear about her lab's exciting vaccine work
mprnews.org/episode/2020/0…
Dr. Fuller's lab recently released an excellent pre-print describing some really fantastic preclinical results from a new #SARSCoV2 vaccine they developed:
biorxiv.org/content/10.110…
This vaccine is like the Moderna vaccine in that it uses RNA to generate immune responses against #SARSCoV2 spike (S) protein, but with a twist. Instead of using messenger RNA (mRNA) to express S, this vaccine uses a RNA replicon. What is that, you ask?
Replicons are self-replicating RNA. mRNA vaccines encode S, but they degrade over time. When they are gone, they're gone, and so is S protein expression. Replicons, on the other hand, keep making new RNA, leading to increased protein expression.
Furthermore, sometimes the immune system doesn't respond robustly to just a viral protein like S alone, so an adjuvant is required to boost what's called immunogenicity, which is the ability of a given antigen to stimulate an immune response.
Replicons have the advantage of acting as their own adjuvants. Replicating RNA isn't normally found in our cells, so we have evolved sensors for it. When replicating RNA is detected by these sensors, it triggers antiviral immune responses.
But wait...how is this different from a replicating virus? Replicons usually replace the structural proteins that form the physical "shell" of the virus with the antigen needed for immunity. So they have the machinery to replicate the RNA, but not to make new virus particles.
But isn't S a structural protein? It is, but this replicon vaccine is made with an alphavirus backbone. Alphaviruses are a totally different virus family, and you can't make an infectious alphavirus particle with coronavirus structural proteins.
What's more, the Fuller lab team formulated this replicon with a lipid nanoparticle (LION) that improves cellular uptake of the vaccine, further increases immunogenicity, and stabilizes it at room temperature for over a week. That's really critical, because RNA is unstable.
The "cold chain" is a major challenge of delivering RNA vaccines. We store RNA in ultralow -80 C freezers in the lab, because it's not stable long-term even at normal freezer (-20 C) or refrigerator (4 C) temperatures. This makes it hard to get vaccines to places...
...where the cold chain can't be preserved. Stability at room temp means this vaccine can be distributed much more easily all over the world. They also developed a "two-vial" system in which the vaccine and the LION reagent can be stockpiled and stored separately until needed.
But the most important question...did this vaccine actually work? Yes it did! This replicon vaccine induced potent neutralizing antibodies in mice (including in aged mice) and in pigtailed macaques with a single dose.
Although the authors have not yet challenged vaccinated animals to assess protective efficacy, those experiments are surely in progress. These results are incredibly encouraging and it's reassuring to know there's another promising vaccine candidate in the pipeline.
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