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

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 clinicaltrials.gov 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.