Thread by @trvrb

I fully agree that the single best action individuals (and governments) can be taking to reduce impact of the Omicron wave is to get booster dose if already vaccinated and to get vaccinated if not. 1/14

However, I absolutely think we need to be moving forward with clinical trials for a possible future swap to an Omicron-specific or bivalent vaccine (nytimes.com/2021/12/20/hea…). 2/14

Given rapid spread there's no possibility of having an Omicron-specific vaccine ahead of the wave, and a booster with the original formulation is shown to produce good neutralization titers against Omicron and largely restore effectiveness against symptomatic disease. 3/14

In neutralization assays, @BalazsLab observes only a 4-fold or 6-fold reduction in titer going from wild-type to Omicron after booster relative to 43-fold or 122-fold after initial mRNA vaccine series (medrxiv.org/content/10.110…). 4/14

Early data from @UKHSA technical report #31 shows that vaccine effectiveness against symptomatic illness after booster is reduced from ~95% against Delta to ~75% against Omicron (gov.uk/government/pub…). 5/14

A 4 to 6-fold reduction in neutralization titer or a ~20% drop in vaccine effectiveness against symptomatic illness is really not bad and I'm happy boosters broaden immunity as much as they do. 6/14

However, in advocating for clinical trials for Omicron booster, I'm really thinking of 9 months down the line. Due to seasonality, waning immunity and further evolution of Delta and Omicron, we will very likely face a SARS-CoV-2 wave in winter 2022-2023. 7/14

Like with seasonal influenza vaccines, we'll want vaccines being deployed to closely match circulating viruses and come September it's very possible we'll have descendants of Omicron, Delta or both circulating. 8/14

https://twitter.com/trvrb/status/1470420216232374281

There will be vaccines being administered in Sep 2022 that will be first doses for some individuals, third doses for others and (conceivably) fourth doses for others still. Having antigen closely match circulating viruses is beneficial for each of these circumstances. 9/14

Given potential for Delta / Omicron co-circulation as well as displacement, I believe clinical trials should compare immune responses to wild-type boost, Omicron-only boost and bivalent wild-type / Omicron boost. 10/14

We may well decide to stick with wild-type vaccine, but we need to conduct these trials in order to make a decision informed by data on the potential improvement in breadth of immune response. 11/14

There are a couple additional benefits to conducting these trials:
1. We can push forward scientific understanding of immunization with different antigenically distinct SARS-CoV-2 strains, as strain update will eventually be necessary
12/14

2. We can better lay groundwork for a rapid vaccine update in the potential future scenario of an Omicron-like variant that emerges but with increased severity
13/14

mRNA vaccines in particular have the potential to be rapidly updated to respond to viral evolution. We're going to be dealing with an evolving SARS-CoV-2 for the foreseeable future. We should tailor our vaccines accordingly. 14/14