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mRNA-1273 vaccine induces neutralizing antibodies against spike mutants from global SARS-CoV-2 variants

Our take —

This study, available as a preprint and thus not yet peer reviewed, demonstrated that sera from both human phase 1 trial participants and non-human primates administered the Moderna mRNA-1273 vaccine were successfully able to neutralize all circulating strains of SARS-CoV-2 shown to date. Neutralizing antibody titers against the South African variant were reduced, but still effective. Titers against all strains, including the South African variant, were still higher than titers that were found to be protective in pre-clinical, challenge studies in non-human primates.

Study design

Other

Study population and setting

This study investigated the ability of sera from humans and non-human primates vaccinated with the Moderna mRNA-1273 vaccine to neutralize known variants of the SARS-CoV-2 virus via VSV-based SARS-CoV-2 PsVn assays. Researchers used eight human sera samples from phase 1 trial participants who got two 100 ug doses in a prime-boost strategy 28 days apart, eight sera samples from non-human primates that got two doses of 100 ug, and four sera samples from non-human primates who got two doses of 30 ug. Spike proteins studied included S protein from the original Wuhan-Hu-1 isolate (D614), D614G variant (dominant strain of 2020), B.1.1.7 (UK variant) and B.1.351 (South African variant), and other variants that have previously emerged (20E, 20A.EU2, DG614-N439K, and mink cluster 5 variant). Single mutations in the S protein were tested as well as combinations and complete sets of mutations present in the receptor-binding domain (RBD) region of the S protein.

Summary of Main Findings

Both human and non-human primate sera were tested against S protein from the Wuhan-Hu-1 strain, D614G variant, 20E, 20A.EU2 and mink cluster 5 variant. Similar levels of neutralization were achieved by both human and non-human primate sera against all these variants compared to the D614G strain. Next, non-human primate sera was tested against S protein from the Wuhan-Hu-1 strain, D614G variant, and single, partial, and complete sets of mutations from the UK and South African variants. There was minimal effect on neutralization of the UK lineage, including key mutations of interest N501Y and the 69-70 deletion. There was a significant decrease in neutralizing antibody titers against the South African variant, but full neutralization was still achieved. Finally, human sera was tested against the UK and South African variants with their complete sets of mutations or specific RBD mutations. There was again minimal effect on neutralization of the UK variant, and a significant decrease in neutralizing antibody titers against the South African variant. However, titers against the South African were still generally high and complete neutralization was still achieved.

Study Strengths

A previous study had investigated the mRNA-1273 vaccine’s efficacy against only a few mutations in known viral variants, while this study now investigated single, combinations, and full spectrums of mutations. Sera from both humans and non-human primates was used. This study also compared neutralization efficiency of sera from humans and non-human primates vaccinated with mRNA-1273 to sera from convalescent plasma donors.

Limitations

A limitation of this study was the small sample size, with only 8 human sera samples and 12 total non-human primate sera samples being used. Additionally, though neutralizing antibody levels are viewed as a correlate of protection, no true correlate of protection against SARS-CoV-2 has been established. Lastly, the system used here was a pseudotyped neutralization study, and these data will need to be repeated using the full viral variant when these become available.

Value added

This is the first assessment of sera from participants who received the Moderna mRNA-1273 vaccine against full spectrum of mutations in the spike protein found in the B.1.1.7 (UK) and B.1.351 (South Africa) variants.

This review was posted on: 28 January 2021