Thread by @DrEricDing

BREAKING—Good & bad news—The Moderna #COVID19 vaccine fully protected against the UK 🇬🇧 #B117 variant... but was 6x less efficient at neutralizing the South African #B1351 variant in lab test. Moderna is testing a newly synthesized booster for it—3rd shot. washingtonpost.com/health/2021/01…

2) To be clear—6x less efficient doesn’t mean no protection against #B11351, it’s still good but not as good as before. As a precaution, Moderna announced it will launch two new studies—including adding a third shot of its current vaccine to boost its two-dose regimen.

3) press release is very cautiously worded—“6-fold reduction in neutralizing titers was observed with B.1.351 variant relative to prior variants. Despite this reduction, neutralizing titer levels w/ B.1.351 remain above levels expected to be protective.”
investors.modernatx.com/news-releases/…

4) “The two-dose regimen of the Moderna COVID-19 Vaccine at the 100 µg dose is expected to be protective against emerging strains detected to date. Nonetheless, Moderna today announced its clinical strategy to proactively address the pandemic as the virus continues to evolve.”

5) “First, the Company will test an additional booster dose of its COVID-19 Vaccine (mRNA-1273) to study the ability to further increase neutralizing titers against emerging strains beyond the existing primary vaccination series.”

6) “Second, the Company is advancing an emerging variant booster candidate (mRNA-1273.351) against the B.1.351 variant first identified in the Republic of South Africa. The Company is advancing mRNA-1273.351 into preclinical studies and a Phase 1 study in the U.S.”

7) “to evaluate the immunological benefit of boosting with strain-specific spike proteins. Moderna expects its mRNA-based booster vaccine (whether mRNA-1273 or mRNA-1273.351) will be able to further boost neutralizing titers in combination with all leading vaccine candidates.”

8) “We are encouraged by these new data, which reinforce our confidence that the Moderna COVID-19 Vaccine **should** be protective against these newly detected variants,” said Stéphane Bancel, Chief Executive Officer of Moderna.

*emphasis mine.

9) “Out of an abundance of caution and leveraging the flexibility of our mRNA platform, we are advancing an emerging variant booster candidate against ( #B1351 variant ) to determine if it will be more effective to boost titers against this and potentially future variants.”

10) “The in vitro study assessed the ability of mRNA-1273 to elicit potently neutralizing antibodies against the new #SARSCoV2 variants, using sera from 8 Phase 1 clinical trial participants (aged 18-55 years) who received two 100 µg doses of mRNA-1273...

11) “and separately using sera from non-human primates (NHPs) immunized with two doses of 30 µg or 100 µg of mRNA-1273.”

➡️They tested blood of both humans and primates who were vaccinated with **2 FULL DOSES**.

12) Pfizer also says their vaccine works against the #B117, however the @GuptaR_lab says they found a ~3.8-fold lower neutralization among blood of 15 Pfizer-vaccinated individuals to the #B117 variant.

https://twitter.com/DrEricDing/status/1351233027410718720

13) But much more worrisome was the recent data that found blood from 48% of people previously recovered from #COVID19 in the 1st 2020 wave in South Africa did not recognize the new #B1351 variant — “complete immune escape”. 90% had lower neutralization.

https://twitter.com/DrEricDing/status/1351282325926146048

14) To be clear, the South Africa research was done by their CDC @nicd_sa and tested the E484K mutation in the #b1351, which is also shared by the Brazil 🇧🇷 #P1 variant. This PQ was the variant also detected in Japan among 🇧🇷 travelers.

https://twitter.com/drericding/status/1348606324901359619

15) But the South Africa 🇿🇦 and Brazil 🇧🇷 variants have worried WHO director @DrTedros enough to put out a warning.

https://twitter.com/DrEricDing/status/1348710699036516355

16) Moderna adds

“For B.1.351 variant... pseudovirus neutralizing antibody titers were approximately 6-fold lower relative to prior variants.

➡️These lower titers may suggest a potential risk of earlier waning of immunity to the new B.1.351 strains.”

17) this is why South Africa’s CDC @nicd_sa put out this stunning statement last week on the “reinfection” potential of the new #B1351 variant. Because of the 48% of recovered #COVID19 patients with “complete immune escape”

https://twitter.com/DrEricDing/status/1351686170044989442

18) Given the similarity of the South Africa 🇿🇦 and Brazil 🇧🇷 variants (they both share the troublesome E484 mutation that has shown antibody escape in 9 out of 11 blood samples from convalescent people), many expect both variants might have vaccine efficacy lowering issues.

19) For the Pfizer vaccine #B117 mutation, there are conflicting studies—Pfizer/BioNTech’s own study shows no drop in B117 neutralization (left), but the @GuptaR_lab study of Pfizer vaccinated patients shows a 3.8-fold drop (right). Trying to figure out why divergent results.

20) there is now also concern the #B117 variant might have roughly a ~30% increased risk of death. 7 out of 10 studies supports it. Here’s the walk thru thread 🧵 on it...

https://twitter.com/DrEricDing/status/1353468238773035008

21) Hence because of the greater contagiousness of #B117 and possible higher mortality risk, we should all upgrade our masks....

https://twitter.com/DrEricDing/status/1353186978519539712

22) Efficacy drop is *NOT* 1/6th of 95%. It’s not a 1/6th direct efficacy correlation.

There are other ways to neutralize a virus like with T cells too—that’s not measured usually. Only a trial can show the % efficacy. I expect it still >50%. Likely 70-90%.

➡️Take the vaccine!