Antibodies elicited by SARS-CoV-2 infection or mRNA vaccines have reduced neutralizing activity against Beta and Omicron pseudoviruses
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Abstract
Multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants that have mutations associated with increased transmission and antibody escape have arisen over the course of the current pandemic. Although the current vaccines have largely been effective against past variants, the number of mutations found on the Omicron (B.1.1.529) spike protein appear to diminish the protection conferred by preexisting immunity. Using vesicular stomatitis virus (VSV) pseudoparticles expressing the spike protein of several SARS-CoV-2 variants, we evaluated the magnitude and breadth of the neutralizing antibody response over time in individuals after infection and in mRNA-vaccinated individuals. We observed that boosting increases the magnitude of the antibody response to wild-type (D614), Beta, Delta, and Omicron variants; however, the Omicron variant was the most resistant to neutralization. We further observed that vaccinated healthy adults had robust and broad antibody responses, whereas responses may have been reduced in vaccinated pregnant women, underscoring the importance of learning how to maximize mRNA vaccine responses in pregnant populations. Findings from this study show substantial heterogeneity in the magnitude and breadth of responses after infection and mRNA vaccination and may support the addition of more conserved viral antigens to existing SARS-CoV-2 vaccines.
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Due to greater vaccine escape of Omicron variants, the cross-neutralizing titre against the Omicron variant is several folds lower than against WT, therefore the decline rate is much faster.
“In addition, due to a greater vaccine escape of Omicron variants, the cross-neutralizing titre against the Omicron variant is several folds lower than against WT, therefore the decline rate is much faster 15 .”
From Safety and immunogenicity of a prefusion non-stabilized spike protein mRNA COVID-19 vaccine: a phase I trial (2022) · cites this paper as [15]
The Results section reports reduced Omicron neutralizing titers relative to D614 and describes fold reductions after vaccination (Fig. 2C). It also reports that titers against all variants waned by day 210 after two vaccine doses, but does not establish that Omicron titers declined faster than WT titers or that a lower starting titer caused a faster decline. (LLM, conf=0.87)
Experimental — accuracy not yet measuredDue to escape of the Omicron variant from current approved vaccines, the efficacy of all current vaccines is reduced and a new variant-specific analysis is required.
“However, due to escape of the Omicron variant from current approved vaccines, the efficacy of all current vaccines is reduced and a new variant-specific analysis is therefore required [13][14][15] .”
From Safety and immunogenicity of a prefusion non-stabilized spike protein mRNA COVID-19 vaccine: a phase I trial (2022) · cites this paper as [15]
The Results report reduced neutralizing antibody responses against Omicron after mRNA vaccination, and the Discussion says mRNA vaccines will likely have somewhat reduced effectiveness against variants as antigenically drifted as Omicron. The paper does not establish reduced clinical efficacy for all current vaccines; it studies neutralization after mRNA vaccination. Its Introduction motivates variant-specific assessment, but does not say that a new analysis is required. (LLM, conf=0.88)
Experimental — accuracy not yet measuredNeutralizing antibody against WT and Omicron induced by 2 doses of approved COVID-19 vaccines wane over time.
“One of the limitations of currently approved mRNA COVID-19 vaccines is that recent data have shown that the neutralizing antibody (NAb) against WT and Omicron induced by 2 doses of approved COVID-19 vaccines wane over time.”
From Safety and immunogenicity of a prefusion non-stabilized spike protein mRNA COVID-19 vaccine: a phase I trial (2022) · cites this paper as [15]
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- Authors
- Sievers, B. L., Chakraborty, S., Xue, Y., Gelbart, T., Gonzalez, J. C., Cassidy, A. G., Golan, Y., Prahl, M., Gaw, S. L., Arunachalam, P. S., Blish, C. A., Boyd, S. D., Davis, M. M., Jagannathan, P., Nadeau, K. C., Pulendran, B., Singh, U., Scheuermann, R. H., Frieman, M. B., Vashee, S., Wang, T. T., & Tan, G. S.
- Affiliations
- J. Craig Venter Institute (US)
- Stanford Medicine (US)
- Department of Medicine, Division of Infectious Diseases, Stanford University, Stanford, CA 94305, USA.
- University of California, San Francisco (US)
- Chan Zuckerberg Biohub San Francisco (US)
- Howard Hughes Medical Institute (US)
- University of Maryland, Baltimore (US)
- Corresponding author
- Wang, Taia T.
- Tan, Gene S.
- ORCID
- Sievers, Benjamin L.
- Chakraborty, Saborni
- Xue, Yong
- Gelbart, Terri
- Gonzalez, Joseph C.
- Cassidy, Arianna G.
- Golan, Yarden
- Prahl, Mary
- Gaw, Stephanie L.
- Arunachalam, Prabhu S.
- Blish, Catherine A.
- Boyd, Scott D.
- Davis, Mark M.
- Jagannathan, Prasanna
- Nadeau, Kari C.
- Pulendran, Bali
- Singh, Upinder
- Scheuermann, Richard H.
- Frieman, Matthew B.
- Vashee, Sanjay
- Wang, Taia T.
- Tan, Gene S.
- Venue
- Science Translational Medicine
- Published
- 2022-03-02
- Volume
- 14
- Issue
- 634
- Pages
- eabn7842-eabn7842
- ISSN
- 1946-6234 (ISSN-L)
- 1946-6242
- PMC
- PMC8891085
- OpenAlex
- W4205576941
- Cited by
- 111
- References
- 35
- Citations by year
- 2026: 3 · 2025: 10 · 2024: 10 · 2023: 24 · 2022: 63
- FWCI
- 13.30
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- Science Translational Medicine (publishedVersion, cc-by)
- medRxiv (acceptedVersion)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- ImmPort
- Funders
- Sanofi
- Gilead Sciences
- Thomas Jefferson University
- Regeneron Pharmaceuticals
- Fast Grants
- National Institutes of Health (75N93019C00076, HHSN272201400008C, ASPR-20-01495)
- Biomedical Advanced Research and Development Authority (ASPR-20-01495)
- National Cancer Institute (U54CA260517)
- National Institute of Allergy and Infectious Diseases (HHSN272201400008C), R03AI146632, 75N93019C00076, R01AI137365, U01AI150741, K23AI076614, U19AI111825, K23AI127886, U19AI057229, P01AI153559, U19AI167903, T32AI007290, K24AI144048)
- 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
- SARS-CoV-2, Omicron variant, Beta variant, Delta variant, neutralizing antibodies, mRNA vaccines, natural infection, antibody escape, booster vaccination, pregnant women, spike protein mutations, vaccine response heterogeneity
- MeSH terms
- COVID-19, SARS-CoV-2, COVID-19 Vaccines, mRNA Vaccines, Adult, Antibodies, Viral, Female, Humans, Pregnancy, Pregnancy Complications, Infectious, Vaccines, Synthetic, Antibodies, Neutralizing, Spike Glycoprotein, Coronavirus
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