mRNA-1273 vaccine induces neutralizing antibodies against spike mutants from global SARS-CoV-2 variants
Open accessAbstract
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the causative infection of a global pandemic that has led to more than 2 million deaths worldwide. The Moderna mRNA-1273 vaccine has demonstrated ~94% efficacy in a Phase 3 study and has been approved under Emergency Use Authorization. The emergence of SARS-CoV-2 variants with mutations in the spike protein, most recently circulating isolates from the United Kingdom (B.1.1.7) and Republic of South Africa (B.1.351), has led to lower neutralization from convalescent serum by pseudovirus neutralization (PsVN) assays and resistance to certain monoclonal antibodies. Here, using two orthogonal VSV and lentivirus PsVN assays expressing spike variants of 20E (EU1), 20A.EU2, D614G-N439, mink cluster 5, B.1.1.7, and B.1.351 variants, we assessed the neutralizing capacity of sera from human subjects or non-human primates (NHPs) that received mRNA-1273. No significant impact on neutralization against the B.1.1.7 variant was detected in either case, however reduced neutralization was measured against the mutations present in B.1.351. Geometric mean titer (GMT) of human sera from clinical trial participants in VSV PsVN assay using D614G spike was 1/1852. VSV pseudoviruses with spike containing K417N-E484K-N501Y-D614G and full B.1.351 mutations resulted in 2.7 and 6.4-fold GMT reduction, respectively, when compared to the D614G VSV pseudovirus. Importantly, the VSV PsVN GMT of these human sera to the full B.1.351 spike variant was still 1/290, with all evaluated sera able to fully neutralize. Similarly, sera from NHPs immunized with 30 or 100μg of mRNA-1273 had VSV PsVN GMTs of ~ 1/323 or 1/404, respectively, against the full B.1.351 spike variant with a ~ 5 to 10-fold reduction compared to D614G. Individual mutations that are characteristic of the B.1.1.7 and B.1.351 variants had a similar impact on neutralization when tested in VSV or in lentivirus PsVN assays. Despite the observed decreases, the GMT of VSV PsVN titers in human vaccinee sera against the B.1.351 variant remained at ~1/300. Taken together these data demonstrate reduced but still significant neutralization against the full B.1.351 variant following mRNA-1273 vaccination.
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Other groups have reported comparable findings with vaccinee and convalescent plasma across various pseudotype and authentic virus assays.
“In addition, similar results have been reported by others using vaccinee and convalescent plasmas and a variety of different pseudotype and authentic virus assays15,31,45–49.”
From mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants (2021) · cites this paper as [45]
Neutralizing activity of vaccinee sera against B.1.1.7 is largely intact, and no adverse effects on current vaccines are expected.
“As for the ramifications of our findings for the protective efficacy of current SARS-CoV-2 vaccines, the neutralizing activity of sera from vaccinated individuals against B.1.1.7 is largely intact and no adverse effects on current vaccines are expected (Fig. 4c), consistent with conclusions that were reached by other studies 34,40,41 .”
From Antibody resistance of SARS-CoV-2 variants B.1.351 and B.1.1.7 (2021) · cites this paper as [34]
The 10.3-12.4-fold loss of activity against B.1.351 is larger than reported results using mutant pseudoviruses.
“On the other hand, the loss in activity by 10.3-12.4-foldagainst B.1.351 is larger than results that were reported using mutant pseudoviruses 34,42,43 .”
From Antibody resistance of SARS-CoV-2 variants B.1.351 and B.1.1.7 (2021) · cites this paper as [34]
Neutralising GMT was below cut-off in most cases after prime dose, but titres substantially increased after boost immunization.
“Neutralisating geometric mean titre (GMT) was below cut-off in most cases after prime dose, but as anticipated, titres substantially increased after boost immunization18.”
From Sensitivity of SARS-CoV-2 B.1.1.7 to mRNA vaccine-elicited antibodies (2021) · cites this paper as [18]
The Moderna mRNA-1273 vaccine induces neutralizing antibodies to SARS-CoV-2 variants with a five- to ten-fold reduction in efficacy against B.1.351 S protein compared with pseudovirus bearing D614G.
“The Moderna mRNA-1273 vaccine also induces neutralizing antibodies to SARS-CoV-2 variants with, however, a five-to ten-fold reduction in efficacy against the B.1.351S protein, when compared to pseudovirus bearing the D614G mutation 27,28 .”
From Sensitivity of infectious SARS-CoV-2 B.1.1.7 and B.1.351 variants to neutralizing antibodies (2021) · cites this paper as [28]
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“…(1) that they were better at infecting people that had been previously infected (V2 and V3) (Cele et al., 2021; Garcia-Beltran et al., 2021; Wibmer et al.; Wu et al., 2021) and/or (2) that they were more transmissible (V1, V2 and V3)(Faria et al., 2021; Pearson et al., 2021; Volz et al., 2021).”
Influential
- Authors
- Wu, K., Werner, A. P., Moliva, J. I., Koch, M., Choi, A., Stewart-Jones, G. B. E., Bennett, H., Boyoglu-Barnum, S., Shi, W., Graham, B. S., Carfi, A., Corbett, K. S., Seder, R. A., & Edwards, D. K.
- Affiliations
- Moderna Therapeutics (United States) (US)
- National Institutes of Health (US)
- Corresponding author
- Edwards, Darin K.
- ORCID
- Venue
- bioRxiv (Cold Spring Harbor Laboratory)
- Publisher
- openRxiv
- Published
- 2021-01-25
- PMC
- PMC7836112
- OpenAlex
- W3121332187
- Cited by
- 419
- References
- 12
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 14 · 2023: 21 · 2022: 102 · 2021: 275 · 2020: 1
- Type
- posted content
- Language
- en
- Open access
- green
- doi.org
- Locations
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed (publishedVersion)
- PubMed Central (submittedVersion)
- Funders
- U.S. Department of Health and Human Services (75A50120C00034)
- Vaccine Research Center
- National Institutes of Health (75A50120C00034)
- Biomedical Advanced Research and Development Authority (75A50120C00034, contract 75A50120C00034)
- NIH Office of the Director
- National Institute of Allergy and Infectious Diseases (75A50120C00034)
- Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
- Keywords
- mRNA-1273 vaccine, B.1.351 variant, B.1.1.7 variant, neutralizing antibodies, vaccine-induced immunity, pseudovirus neutralization, non-human primates
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