First multivalent vaccine with a variant (B.1.351) begins: Will it protect against other E484K variants?

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By Daniel R. Lucey MD, MPH, FIDSA

On March 10 Moderna announced that it had begun vaccinating volunteers in a study of 60 persons previously “vaccinated with mRNA-1273 to receive a single booster dose of either:

  • 20 µg of a variant-specific booster candidate, mRNA-1273.351, based on the B.1.351 variant first identified in the Republic of South Africa (N=20)
  • 50 µg of mRNA-1273.351 (N=20)
  • 50 µg of a multivalent booster candidate, mRNA-1273.211, which combines mRNA-1273, Moderna’s authorized vaccine against ancestral strains, and mRNA-1273.351 in a single vaccine (N=20)”.

This study is the first in the world to give a variant-specific vaccine either alone or as part of a multivalent (bivalent in this case) vaccine.

In partnership with the National Institutes of Allergy and Infectious Diseases, Moderna’s announcement says, it will study these variant-specific vaccines in (immunologically “naïve”) persons not previously vaccinated against SARS-CoV-2:

“In parallel, NIAID, part of the National Institutes of Health (NIH), will conduct a Phase 1 clinical trial to assess the monovalent and multivalent modified mRNA-1273 vaccines as a primary series in naïve individuals and as a booster vaccine in those previously vaccine with mRNA-1273. NIAID will initiate this study after receiving safe-to-proceed authorization from the FDA. NIAID will provide additional information when the trial begins. The identifier is NCT04785144.”

This B.1.351 variant, now dominant in S. Africa, contains a mutation E484K (“eek”) in the receptor binding domain that confers some decrease in antibody-mediated immunity.  Multiple other variants also contain this E484K mutation, including the P.1 variant dominant in parts of Brazil, and the B.1.526 variant reported to be increasing in NYC. Although these variants have other non-shared mutations, any degree of cross-protection offered by this B.1.351 variant vaccine against the P.1 and B.1.526 variants would provide valuable information from both a public health and immunology perspective.

Related viewpoints were posted here Feb. 25 and 28, and March 2 and 3.

Dr. Daniel Lucey

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.


One thought on “First multivalent vaccine with a variant (B.1.351) begins: Will it protect against other E484K variants?

  1. Paul Wolf

    How does this work? Is there an abbreviated approval process, or does this have to be followed by phase 2 and/or phase 3 clinical trials?

    Taking Manaus as an example, the P1 variant arrived in a “second wave” only after most of the population had been infected and developed some immunity. This was only admitted very recently – for six months or more they’ve been saying that the 2nd wave last summer wasn’t caused by P1. So the places where most people have developed immunity or been vaccinated, are ripe for E484K coronavirus variants to spread. We have to have these new vaccines ready to go, because once we have vaccinated most people in a few months, that’s when we’ll see the E484K waves.


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