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Monica Gandhi MD, MPH Profile picture
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12 Feb, 4 tweets, 1 min read
This study is going to tickle your T cells! A lot of what will happen with the variants will be determined by how well your vaccine-induced T-cell response cross reacts to them. Here is UK study of vaccinated people (Pfizer x 2) then exposed to new
researchsquare.com/article/rs-226…
variants circulating (B.1.1.7 UK, B.1.351, SA) compared to cohort who recovered from natural infection (with non-variants) in spring 2020. Those who had recovered from natural infection with the "spring" (non-variant) virus had less effective antibody responses (reduced with UK
variant, couldn't neutralize the B.1.351 strain). But T cells remained protective likely because it forms responses to epitopes ('bits') across the whole spike protein. Same true with those who got 1 dose of vaccine- robust and complex T-cell response to the variants
Reminds one of that study I tweeted before with the incredible breadth of response (30-40 epitopes recognized) by both CD4 and CD8 cells with natural infection
sciencedirect.com/science/articl…

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More from @MonicaGandhi9

Monica Gandhi MD, MPH Profile picture
1 Feb
okay let's put it specifically from NYT since everyone thinks I am Pollyanna: "In official language of research science, vaccine is typically considered effective only if it prevents people from coming down with any degree of illness..."
nytimes.com/2021/02/01/bri…
"With a disease that’s always or usually horrible, like ebola or rabies, that definition is also the most meaningful one.
But it’s not the most meaningful definition for most coronavirus infections. Whether you realize it or not, you have almost certainly had a coronavirus. "
"Coronaviruses have been circulating for decades if not centuries, and they’re often mild. The common cold can be a coronavirus. The world isn’t going to eliminate coronaviruses — or this particular one, known as SARS-CoV-2 — anytime soon. Yet we don’t need to eliminate it for"
Read 5 tweets
Monica Gandhi MD, MPH Profile picture
1 Feb
Efficacy refers to how a drug/vaccine does in a clinical trial; effectiveness refers to how it does in the "real world". Nice preprint on the effectiveness on the Pfizer vaccine which has arrangement with Israel to get data weekly as it rolls out
medrxiv.org/content/10.110…
503,875 individuals (mean age 59·7 years); 351,897 had 13-24 days of follow-up. Cumulative incidence of infection was 0·57% days 1-12 and 0·27% days 13-24. Relative risk reduction 51.4% after 1st dose with more expected after 2nd. Real world looks as good as trial, exciting!
By the way, for my academic friends, this is clearly being reviewed at Lancet with the decimal point in the middle and the "evidence before this study" part at the beginning!
Read 6 tweets
Monica Gandhi MD, MPH Profile picture
1 Feb
One thing that struck me tonight is that the UK roll-out of vaccine is much more in line with public health and practicality than US rollout which is much more 'academic'. For those in academia, you know what I mean but we pay attention to every single detail of the trials-
In fact, an academic ID doctor worth their salt better know which HIV trial of the new injectable HIV medications allowed in a K103N mutation or not. However, when it comes to achieving herd immunity, we do not need 100% of the population to have 100% protection- we need as many
people as possible to get vaccinated as soon as possible with any of these vaccines, all of which encode for the entire spike protein and are very immunogenic. So, the UK authorized AZ/U of Oxford vaccine, Moderna, & Pfizer because the more you authorize the more supply you have.
Read 7 tweets
Monica Gandhi MD, MPH Profile picture
30 Jan
And then wanted to explain why you should be beaming ear-to-ear about vaccine data. Why would an infection trigger all of this testing, masking, life halting? Because severe illness/hospitalizations/deaths occur. All vaccines to date prevented hospitalizations/deaths completely.
Severe illness prevented completely in Moderna/Pfizer/AztraZeneca trials; 85% across regions (even in South Africa - South Africa variant there) in J&J trials and immune response from 1 dose may keep on giving (remember, outcomes evaluated 14-28 days out due to expediency)
But as I wrote yesterday, immunogenicity from 1 dose of J&J likely extends beyond 14-28 days - keeps on going so likely more protection over time - see graphs in this paper. Two-dose trial still going. Finally, S. Africa variant is one with less protection
nejm.org/doi/full/10.10…
Read 6 tweets
Monica Gandhi MD, MPH Profile picture
30 Jan
Know very tempting to feel nervous about variants. Please don't: 1) RNA viruses do mutate and those more fit spread more readily; 2) SARS-CoV-2 has much lower mutational rate than influenza A - we are seeing more because transmission high, want to tamp down (& now sequencing);
3) Vaccines do not generate just antibody response, but T cell responses (measured in all 3 trials published) and B cell responses). So if neutralizing antibodies slightly lower in vaccinated blood to a variant (and not yet lower in clinically significant way), remember T cells.
4) So far, all of these vaccines involve genetic material that code for the spike protein/RBD- mRNA in mRNA vaccines and double-stranded DNA in adenovector vaccines. Sequences of genetic material can be "tweaked" to respond to variants as needed; 5) As tweeted before, efficacy
Read 4 tweets
Monica Gandhi MD, MPH Profile picture
29 Jan
Wonderful news about the Johnson&Johnson vaccine! Let me explain (and also let me tell you I was just on an interview with Dr. Paul Offit, who believes - like me- that control is nigh). J&J vaccine press release here:
jnj.com/johnson-johnso…
J&J vaccine is a modified cold virus adenovirus (this vector doesn't replicate or cause illness in humans) with double stranded DNA coding the spike protein of SARS-CoV-2 inside. Nice explanation of NYT of how it works. The adenovirus "vector" (carrier)
nytimes.com/interactive/20…
gets the DNA inside host cell nucleus where it is "transcribed" into mRNA and then you make the spike protein of the virus % raise immune response against it. Initial phase I/II data from NEJM showed high immunogenicity of 1st dose that went up over time.
nejm.org/doi/10.1056/NE…
Read 10 tweets

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