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Rajeev Venkayya MD Profile picture
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29 Jan, 8 tweets, 3 min read
THREAD
In light of the exciting & sobering news from @Novavax and @JNJNews, some thoughts on implications for future vaccine development.

As I've said, the Ph3 trials will provide the highest-quality data on vaccine efficacy against the new variants. 1/
Multiple lines of evidence strongly suggest mutations in B.1.351 confer some escape from natural and vaccine immunity.

Unless shown otherwise in efficacy/effectiveness studies, we should assume this is a class effect for all spike-targeting vaccines. 2/
The good news is we're likely to see higher levels of vaccine efficacy against variant-associated severe disease and death. J&J has provided the first evidence of this in their press release (insufficient severe dz in the Novavax interim analysis). 3/
But the virus will continue to mutate with pressure from natural+vaccine immunity, and there's no guarantee current efficacy will be maintained. We need to establish a rapid "strain-change" mechanism with ongoing safety & effectiveness monitoring. 4/
We also need to quickly establish correlates of protection that allow us to forgo efficacy trials for new vaccines. Warp Speed is working on this, and the variant-associated vaccine "breakthrough" cases will inform those analyses. 5/
These findings have major implications for future Ph3 studies & supply. For those vaccines that aren't in Ph3, developers and regulators have to ask whether they take their original construct/formulation into Ph3 or update to cover the new variants. 6/
If regular boosters are needed for new variants and to maintain immunity, this will widen the supply-demand gap even further. We must avoid a situation where people who haven't received their first dose are losing out to those receiving boosters for variants. 7/
These impressions are subject to change as we learn more about the vaccines in development and immunity.

But the bottom line is that we’ve taken another huge leap forward in the effort to protect the world against this virus. 8/

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More from @rvenkayya

Rajeev Venkayya MD Profile picture
6 Jan
@BhadeliaMD @kavitapmd @ashishkjha @ASlavitt @RanuDhillon @RebeccaKatz5 Manufacturing partnerships are necessary for any company to ramp up manufacturing of #COVID vaccines, since no company has enough capacity to meet the world’s needs. Nearly all vaccines in late-stage trials have partnerships in place for this purpose. 1/ 🧵
@BhadeliaMD @kavitapmd @ashishkjha @ASlavitt @RanuDhillon @RebeccaKatz5 .@Novavax is a good example (@AstraZeneca is another). They listed their network of partners when they announced the partnership with @SerumInstIndia, with a goal of manufacturing >2B doses/yr. (@TakedaPharma is one of those partners.) 2/
ir.novavax.com/news-releases/…
@BhadeliaMD @kavitapmd @ashishkjha @ASlavitt @RanuDhillon @RebeccaKatz5 @Novavax @AstraZeneca @SerumInstIndia @TakedaPharma But it would be hard to quickly expand supply through new partnerships for several reasons:

TIMELINES: Depending on maturity and complexity of the process and partner capabilities, it takes a *minimum* of several months to transfer manufacturing to a new partner & facility. 3/
Read 8 tweets
Rajeev Venkayya MD Profile picture
3 Jan
THREAD
I created a simple table to illustrate the individual impact of the "flexible second dose timing" now recommended in the UK.

Coincidentally, @bob_wachter & @ashishkjha just tackled the US policy question in this important piece. 1/
I based this on recent statements from the UK chief medical officers, JCVI, and what we know from prior vaccine development. 2/

JCVI: app.box.com/s/iddfb4ppwkmt…

UK Chief Medical Officer (CMO) statement: gov.uk/government/new…

CMO letter to the profession: gov.uk/government/pub…
This table and thread focuses on the AZ vaccine, where more data on a delayed second dose is available than with the Pfizer vaccine. It is not intended to address questions about single-dose regimens or mix & match approaches. 3/
Read 18 tweets
Rajeev Venkayya MD Profile picture
1 Jan
THREAD
There’s much debate around the UK's recommended use of the AZ vaccine with a two-dose schedule and flexible timing of second dose. Some thoughts on the AZ recommendation (not Pfizer) based on available data with refs to some excellent threads. 1/
UK’s MHRA and JCVI are highly-experienced in vaccine assessments and recommendations, and they've surely weighed the benefits & risks of this recommendation carefully. That said, it would be good to see all the data underpinning their recommendation. 2/
In general, vaccines should be taken on a schedule tested in an efficacy trial. But it wasn’t possible to conduct the typical dose and schedule optimization prior to these Ph3 trials, and those trials provided valuable data to inform these recommendations. 3/
Read 14 tweets
Rajeev Venkayya MD Profile picture
28 Dec 20
THREAD
As scientists race to understand the new COVID variants, we have a valuable tool at hand: multiple ongoing Phase 3 vaccine trials. These can provide valuable insights into vaccine protection as well as the natural epidemiology of the variants via the placebo arms. 1/
The first indication of whether vaccine protection is affected will come from the lab: neutralization studies assessing whether vaccine-induced antibodies are as effective at neutralizing the new variant as earlier strains of SARS-CoV-2. Similar activity will be reassuring. 2/
But neutralization assays only assess the antibody contribution to protection, and they won’t measure transmissibility of the new variant. Animal models can provide some information, but definitive answers will only come from clinical and epi studies. 3/
Read 11 tweets
Rajeev Venkayya MD Profile picture
12 Dec 20
I've participated in some great discussions on #COVID19 and #vaccines on #Clubhouse recently. I’ll use this thread to share some references I’ve mentioned and/or plan to bring up in future rooms. @joinClubhouse 1/

@JorgeCondeBio
First up is a new tool from @bhrenton that tracks #CovidVaccine allocations to US states, and *some* distribution sites, based on publicly-available sources and pending a federal tracking website. 2/

Next up is a link to the Black Coalition Against Covid (@BCAgainstCOVID), which I learned about when I was on a panel with its cofounder @DrReedTuckson. It has a number of good resources including a great town hall on COVID-19 vaccine development. 3/
Read 7 tweets
Rajeev Venkayya MD Profile picture
6 Dec 20
THREAD

Swiss cheese is great for explaining how to slow a virus, as @MackayIM's fantastic graphic shows.

There's a history. Dr. Carter Mecher first applied Swiss cheese to pandemics in 2006 at the White House. I told the story @statnews in April. 1/

statnews.com/2020/04/24/swi…
Carter came across James Reason's work in human failures and complex systems when he worked on patient safety at the Dept of Veterans Affairs.

Swiss cheese was a good way to explain the power of early coordinated NPIs in a pandemic, which was called "community mitigation." 2/
Community mitigation came out of @DrRHatchett's work to understand the impact of combined NPIs. In 2006 Richard commissioned NIH-funded MIDAS modelers (3 groups) to model NPIs at different points in time. 3/

@PNASNews @betzhallo @neil_ferguson @ilongini

pnas.org/content/105/12…
Read 6 tweets

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