By Daniel R. Lucey MD, MPH, FIDSA
On Friday (Feb. 26) National Institute of Allergy and Intections Diseases Director /NIH Dr. Anthony Fauci, announced plans to start vaccine studies for the first time using the variant B.1.351, now dominant in South Africa and present in the United States. It contains the E484K mutation and also the 501Y mutation both of which are found in the P.1 variant dominant in Manaus, Brazil and present in the U.S.
This is the first vaccine that includes this antibody-impairing E484K mutation, and also the 501Y mutation that enhances binding to the ACE2 receptor on human cells and thereby likely increases transmissibility of these variants. As such, I think we can learn to what extent immunity from this vaccine against B.1.351 can also protect against the P.1 variant, and others.
At Friday’s White House COVID-19 press briefing, Dr. Fauci stated that two cohorts would be studied:
Cohort 1 will be in persons previously vaccinated with the Moderna vaccine in their Phase 1 study a year ago. It will enroll volunteers in Atlanta and Seattle.
Arm 1a will give 30 volunteers a 50mcg booster dose of the new variant-specific “mRNA-1273.351” vaccine.
Arm 1b will give 30 volunteers 25mcg each of both the original Moderna mRNA-1273 vaccine and also the new mRNA-1273.351 vaccine.
The outcome measurement will be to compare the virus neutralization of the original SARS-CoV-2 strain and the B.1.351 variant.
Cohort 2 will be in volunteers never-vaccinated and never-infected with SARS-CoV-2. This cohort will enroll more patients (150 total) in more cities (Cincinnati and Nashville, as well as Atlanta and Seattle) than Cohort 1.
Volunteers will be randomized to six distinct “prime-boost” strategies using different combinations of mRNA-1273 and mRNA-1273.351. Further breakdown of these six groups was not specified. The outcome measurement will be the same as Cohort 1.
To emphasize, the importance of this variant-specific vaccine could extend beyond the B.1.351 variant alone. Why? The reason is because this is the first vaccine that includes this antibody-impairing E484K mutation, and also the 501Y mutation that likely increases transmissibility of these (and other) variants. As such, I think we can learn to what extent immunity from this vaccine against B.1.351 can also protect against the P.1 variant, and other variants such as the small percentage of the B.1.1.7 variant in the UK reported to have acquired the E484K mutation.
Daniel Lucey, M.D. MPH, FIDSA, FACP, is a Clinical Professor of Medicine at Dartmouth Geisel School of Medicine, Infectious Disease adjunct Professor at Georgetown Medical Center, senior scholar at Georgetown Law, Anthropology Research Associate at the Smithsonian Museum of Natural History and a member of the Infectious Diseases Society of America Global Health Committee. He served as a volunteer to outbreaks overseas including hands-on Ebola patient care in Sierra Leone and Liberia (Doctors without Borders) 2014, MERS 2013, SARS 2003, as well as HIV, H5N1, Zika, yellow Fever, and pneumonic plague 2017 (with WHO/USAID/CDC). Since Jan. 6, 2020 he has contributed over 75 posts to Science Speaks on COVID-19 and traveled to China in February 2020. He initially proposed, then fundraised and helped design the content for 2018-2022 Smithsonian Exhibition on Epidemics due to zoonotic viruses. From 1982-1988 he trained at University of California San Francisco and Harvard and was an attending physician at the NIH (NIAID) in the 1990s while in the US Public Health Service.