Why should we not worry about VARIANTS "escaping" immunity from vaccines or natural infection; why are we not likely to need vaccine BOOSTERS? Remember immunity is both antibody and cell-mediated (CD4 and CD8 cells). Long-term immunity mediated by memory B & T cells (both get
stimulated if they see the virus again). We now feel secure that T-cell immunity will be preserved against variants after these 2 papers reassured us. Sette's great paper showing T-cell immunity after natural infection or mRNA vaccination preserved against biorxiv.org/content/10.110…
B.1.1.7 (UK), B.1.351 (South Africa), P.1 (Brazil), and CAL.20C (California). Means T cells generated by vaccines can readily fight these variants. 2nd paper is by Dr. Redd one showing that CD8 responses preserved despite spike protein mutations
in B.1.1.7 (UK), B.1.351 (S. Africa), P.1 (Brazil);Basically, your T cell response is so complicated & varied across the spike protein, a few mutations don't matter. Could be true of antibodies too; we just only measure a few (remember that); T cells assays in labs reveal breadth
I tweeted 3rd paper that showed this back in Feb. This was written at a time UK was worried about vax not working against B.1.1.7 and B.1.351. After vaccine, "the majority of the T cell response was directed against epitopes conserved" across variants.
"However, after single vaccination, which induced only modestly neutralizing homotypic antibody titers neutralization against the variants of concern was completely abrogated in the majority of vaccinees". So, T cells after vax neutralize variants. 4th paper that showed this next
And T cells generated by AZ vaccine: "of 87 spike-specific antigens [T cell epitopes] identified by the sequencing, 75 remained unaffected by the B.1.351 mutations" (South Africa) variants in the South Africa trial
And finally, this large 6-month analysis of the real-world effectiveness of the Pfizer vaccine across multiple settings shows high effectiveness against the B.1.351 (E484K containing, S. Africa) variant. Will we need boosters? Likely not- continue tomorrow
But this very famous long-time virologist Dr. Vincent Racaniello was a bit more forceful than I just was when he said- please stop with the variants!
Wanted to add to this thread on how vaccines cover variants (see above, T cells) to explain why we are unlikely to need yearly boosters. #1 - vaccines cover variants. As cases come down, less chance virus to mutate; #2- coronavirus doesn't mutate readily
Coronaviruses actually have a strong "proofreading" mechanism, meaning they don't tolerate mutations and go back and fix them unlike influenza (another RNA virus with a very "leaky" or mutation-prone polymerase or replicating mechanism); #3 - we should have long-lasting immunity
Remember my ode to memory B cells when I cheated on T cells and told you about them. We know that memory B cells generated by these vaccines because these researchers actually biopsied lymph nodes of brave volunteers to prove it! And we know memory B
cells can trigger immune responses DECADES later if see virus again. So, don't think we are going to be needing yearly booster shots for #covid19. And probably need better global flu vaccine too. Hope this thread relieves some tension on variants/boosters
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More from @MonicaGandhi9

7 Apr
Let's talk B117 and why I don't think this variant is going to deter our progress. What are 3 things you worry about with a variant? 1) Increased transmissibility; 2) Increased virulence; 3) Can escape immunity from your vaccine (or natural infection). Let's take them 1 at a time
1) Increased transmissibility: There is lab data showing higher viral loads with this variant in nose so could be more infectious. However please look at epidemiology on world stage and in U.S. to make your decisions. UK tamped down virus with vaccines with 90% of their strains
being B117 and never saw their dreaded surge once vaccine roll-out started; 2) Israel started rolling out vaccine with 80% of strains being B117, saw surge as we are seeing in some states here (will get to that in min.) but then tamped down with vaccine
Read 15 tweets
5 Apr
Let's look at CDC data on "inflection point". Is there a pattern emerging whereby those who are getting close to 40% 1st dose vax rate are seeing turn-around in cases (read below on inflection point). We've already seen hospitalizations per case decrease
due to vaccinations, which is why we know B117 is not creating more virulence (not more hospitalizations per case) although certainly seems more transmissible which is why you want to vax FAST with your restrictions. Data sources: beta.healthdata.gov/browse & covidtracking.com/data/state/tex…
&, Let's look at
*7 day average of cases, comparing to an earlier 7 day average, to get test/positivity rate comparison from different times during the pandemic.
*Number of days in a downward trajectory.
*Positivity rate by week for the last 6 weeks
Read 12 tweets
4 Apr
Wanted to address question of "should I get vaccinated if I have had #covid19"?. Fair question given that immunity likely long-lived from natural infection per this study from Drs. Weiskopf, Sette, & Shane Crotty from the La Jolla Institute for Immunology
And other evidence laid out in this thread. However, I would take the vaccine (1 dose) if I had COVID-19 in the past personally. Why? Because I hate COVID and vax can serve as major immune response booster when a virus is still circulating at high rates
See difference between now & any other time in history is that we are giving out vaccine AS CASES are still circulating high rates. So unprecedented! In fact those who had chickenpox as child (like me, I am old enough!) were not offered VZV vax because I have natural immunity
Read 6 tweets
4 Apr
4 reasons Giants stadium should not ask for random testing of fans in SF to come to games (fans have to pay for their tickets and tests too!):
1) Masks, distancing, ventilation (being outside!) work
2) Being outside is safe
Remember, outside transmission is rare (20x less than inside transmission and likely much less). In fact, the WHO does not even recommend masking outside unless you can't distance and the Giants stadium is planning on masks, small pods
3) We are all getting vax or at least whoever wants vax >16 can get one as of April 15. We have learned by now that your viral load in your nose if you have exposure after vaccination is very low and non-infectious. Fans + noninfectious test = anxiety
Read 4 tweets
3 Apr
Still trying figure out that "inflection" point where vaccines given out enough to population that cases decrease (again, irrespective of lockdown in a way, right, because nursing homes very locked down in US & cases plummeted after vaccine roll-out reached certain threshold)
This article in Nature from very early on in the Israel roll-out (they were far & away ahead of us by then though), says "You need to vaccinate much more than a third of the population to really see a reduction in transmission"
US is right now at 31.4% first dose, 18% fully vaccinated per CDC vaccine tracker but that of course wildly fluctuates per county & state since our public health system is so local-based (federal responses work better in pandemics but not how US built)
Read 19 tweets
3 Apr
I have idea that could decrease cases right now in states that have increasing cases, which is to switch to giving out the 1st dose now & wait on 2nd dose to immediately expand number vaccinated in each of those states now. Let me explain: map of US cases
Here is the WaPo tracking site on vaccination rates by county. 4 reasons for giving 1st dose now in those counties & waiting on 2nd are 1) "Based on immunologic principles, sensitization with single doses would still allow boosting with a 2nd dose
several months later" (please see great Dr. Plotkin article). 2) "B-cell memory after mRNA vaccination has been clearly demonstrated, which supports the idea that antibodies will be boosted by a second mRNA dose given months later" (remember B cell paper)
Read 7 tweets

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