Thread by @EricTopol

On the #SARSCoV2 immune response and vaccine I just did a podcast with Dennis Burton, a leading immunologist and vaccinologist and co-faculty @scrippsresearch. We covered so much a long🧵summary was needed
soundcloud.com/prescrippsions… 1/x

Optimism. "The pandemic is not going to be with us forever"
(This comes from a leader of the HIV vaccine program) 2/x

1st line of defense, interferons: will they likely be helpful given as an early intervention?
Yes, but we have to be very careful 3/x

The real deal—neutralizing antibodies—"recognize danger and get rid of it." Stop the virus from gaining entry into target cells. They are only a fraction of the antibodies anyone makes in response to the virus, some are made to viral debris, breakdown products 4/x

How do we engineer the best, potent neutralizing antibodies?
Structural biology, 3D crystal structure of patient-derived has helped guide the way
The spike protein's binding to ACE2, the receptor binding domain (RBD-A epitope), is a prime target 5/x

One of the neutralizing antibody programs uses a cocktail, not just a single, of monoclonal antibody. That's due to concern about escape variants of the virus. Is that something to worry about?
It's hotly debated whether we need that, like an insurance policy 6/x

The virus is currently slowly evolving but that could change in response to pressure: "They have to change in order to keep going you know, selfish DNA. That's what viruses do" 7/x

Onto T cells, we discussed the recent cross-reactive T cell work (vs common cold coronaviruses) by @profshanecrotty and colleagues. The ones of interest CD8+ are cytotoxic that work on infected cells, but very different than neutralizing antibodies attacking the virus itself 8/x

What would be the ideal profile for a vaccine with respect to both antibodies and T cells?
"I think probably...is best...combine a good antibody response with a good T cell response that gives the greatest possibility for controlling the infection." 9/x

But we don't know. Biggest point of emphasis here:
10/x

What can we extrapolate from other virus vaccines?
Some are superhuman, i.e. better than what a human produces
You can have low antibody response and it be very effective (like HPV). 11/x

What about untoward effects of the vaccine, antibody-dependent enhancement (ADE)? Or immune complex disease? Are you worried about these? 12/x

What if you give the vaccine to someone who has already developed in immune response from #covid19? Or someone that has received neutralizing antibodies? 13/x

You've been working on the HIV vaccine for some time? Why is it so difficult and now there's optimism?
This was fun to get Dennis's perspective on structural biology and rational vaccine design 14/x

What do you think explains the enduring and at times disabling symptoms after covid-19 #LongCovid? We discussed @VirusesImmunity hypotheses. 15/x

Just like the podcasts done with Tony Fauci and Akiko Iwasaki, I was left with a very upbeat sense, and remain impressed how far we have come so fast 16/f
video
transcript scripps.edu/covid-19/video…