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Shane Crotty Profile picture
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16 Feb, 8 tweets, 2 min read
This was really PHENOMENAL news. A big deal for the future of vaccine development broadly. And a big deal in the HIV vaccines field.🧵
Not only was a positive signal seen in 97% of vaccinated people, the signal was fantastically strong!
As noted by Bill Schief in his talk, this is probably the first vaccine trial to succeed in confirming its intended mechanistic hypothesis. A big moment for germline targeting vaccine design strategies!
We helped contribute to this project advancing to human clinical trial with our work in 2016

science.sciencemag.org/content/351/62…
showing that your average person has rare B cells that could recognize this engineered vaccine--and not other engineered vaccines--with significant affinities (Kd ~1 micromolar).
We interpreted as this Schief vaccine protein design achieving a high bar worthy of advancement to human clinical trial.
And we showed in an animal model with a "rare, physiological precursor frequency and affinity" that the vaccine protein succeeded. We predicted those were very encouraging indications for the pending human clinical trial.

doi.org/10.1016/j.immu…
Massive congratulations to Prof. Schief and his team for their amazing success after many years of hard work!

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More from @profshanecrotty

Shane Crotty Profile picture
8 Feb
Well, that's a nice surprise!
What happens if you have had COVID infection before and you get a COVID vaccine?
Some observations last week are summarized here:
In a new pre-print by the excellent @McGuire_Lab , they report a big jump in neutralizing antibodies after a single COVID RNA vaccine immunization (Pfizer or Moderna).

That is the same thing observed by @florian_krammer and the Sajadi labs.
medrxiv.org/content/10.110…
Read 5 tweets
Shane Crotty Profile picture
8 Feb
The AstraZeneca/Oxford (AZ) COVID vaccine (ChAdOx) results in South Africa are concerning. 🧵

* The AZ vaccine had 75% efficacy against mild COVID through October 2020.

* But only 22% efficacy more recently, with the SA variant  (aka B1351 or 501Y.V2)

facebook.com/HealthZA/video…
Penny Moore and Alex Sigal and colleagues now report on antibodies from AZ ChAdOx vaccinated people, and there was a dramatic loss of function against the B1351 variant. It appears to be more than a 20x reduction. A complete loss of neutralization in most individuals (~80%).
First, what to think of the antibody neutralization loss?

It is much steeper than reported by multiple groups elsewhere for COVID19 cases or other COVID vaccines. Multiple labs reported ~2x drop in neutralization of B1351 or related virus, with antibodies from vaccinated people
Read 16 tweets
Shane Crotty Profile picture
8 Feb
This is a very nice study of the AstraZeneca/Oxford (AZ) ChAdOx vaccine in the UK (with a  challenging title!).
ssrn.com/abstract=37791…

There are several novel findings in this study, including:
* 75% protection against ASYMPTOMATIC infections, (w/new definition).

* Protection against symptomatic infections was similar for B117 (the UK variant).

* Even though ChAdOx antibodies were 9x weaker against B117.

* Protection against asymptomatic B117 appears mostly lost.
On the topic of vaccine protection from asymptomatic infections:

There have been limited data on vaccine protection from asymptomatic infections, which has important implications for transmission of virus.
Read 20 tweets
Shane Crotty Profile picture
7 Feb
I am a big fan of this COVID immunity paper from @Anto_Berto . This was the first paper to longitudinally track viral loads AND virus-specific T cells in COVID patients quantitatively in the same study, from early time points. 🧵

@bertoletti_lab

doi.org/10.1016/j.celr…
The key observations are:

* Early T cell responses were associated with rapid control of virus and mild disease.

* Early antibody responses did not distinguish control of virus or disease severity.

* Peak viral loads were correlated with disease severity.
I talk about the importance of longitudinal studies from early timepoints post-infection in this review.

doi.org/10.1016/j.cell…
Read 7 tweets
Shane Crotty Profile picture
5 Feb
Hooray, the shiny colorful final version of our paper is out in Science! 😁🧵
science.sciencemag.org/content/371/65…
Explainer thread when it was first published in Science:
And the even earlier story in the NYT by @apoorva_nyc

Read 4 tweets
Shane Crotty Profile picture
4 Feb
Getting lots of questions about COVID vaccine safety, which is good! Here's a quick compilation of some resources on COVID vaccine safety.🧵
This covers the basics about the RNA vaccines and safety:

I did a Youtube video on RNA vaccines and COVID vaccine safety with the excellent @MedCramVideos . It has been very popular
(over 1 million views!)
Read 8 tweets

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