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Cited by 111SARS-CoV-2 and COVID-19 ResearchAnimal Virus Infections Studiesvaccines and immunoinformatics approaches

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Antibodies elicited by SARS-CoV-2 infection or mRNA vaccines have reduced neutralizing activity against Beta and Omicron pseudoviruses

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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.·2022·Science Translational Medicine
DOI 10.1126/scitranslmed.abn7842PMC PMC8891085

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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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Crossref · 10.1126/scitranslmed.abn7842

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Figures

Fig. 1. Plasma neutralizing titers against variants of concern wane over time in samples from an outpatient COVID-19 infection cohort. (A) Study participants were enrolled (day 0) within three days of a positive SARS-CoV-2 PCR test (+PCR). Longitudinal plasma samples from day 28 (n=23), day 210 (n=23) and day 300 (n=8) were assessed against D614, Delta, Beta and Omicron. (B) The kinetics of half-maximal SARS-CoV-2 pseudovirus neutralizing titers (pNT50) over time are shown. Dotted lines indicate baseline mean pNT50 obtained from seronegative subjects. Solid lines connect samples from the same participant. (C) Mean pNT50 values are shown across study time-points of all 4 pseudovirus variants. Values that were significantly different from D614 at each time point are marked with a star. (D) Ratios of pNT50 values of the indicated variants of concern over D614 pNT50 at each study time point are shown. Horizontal bars indicate median values. p values in (B to D) were calculated using mixed effects analysis with Geisser-Greenhouse correction and Tukey’s multiple comparisons test. *P < 0.05, **P < 0.01.
Fig. 1. Plasma neutralizing titers against variants of concern wane over time in samples from an outpatient COVID-19 infection cohort. (A) Study participants were enrolled (day 0) within three days of a positive SARS-CoV-2 PCR test (+PCR). Longitudinal plasma samples from day 28 (n=23), day 210 (n=23) and day 300 (n=8) were assessed against D614, Delta, Beta and Omicron. (B) The kinetics of half-maximal SARS-CoV-2 pseudovirus neutralizing titers (pNT50) over time are shown. Dotted lines indicate baseline mean pNT50 obtained from seronegative subjects. Solid lines connect samples from the same participant. (C) Mean pNT50 values are shown across study time-points of all 4 pseudovirus variants. Values that were significantly different from D614 at each time point are marked with a star. (D) Ratios of pNT50 values of the indicated variants of concern over D614 pNT50 at each study time point are shown. Horizontal bars indicate median values. p values in (B to D) were calculated using mixed effects analysis with Geisser-Greenhouse correction and Tukey’s multiple comparisons test. *P < 0.05, **P < 0.01.CC BY · PubMed Central
Fig. 2. Plasma neutralizing titers against variants of concern increase after mRNA vaccination in a cohort of pregnant women. (A) Samples collected from a cohort of vaccinated pregnant women at baseline (n=9) and after 2 doses of mRNA vaccine (n=33) were assessed for neutralizing antibody against 4 SARS-CoV-2 pseudovirus strains. (B) pNT50 values of paired samples at baseline and after 2 doses of mRNA vaccine (PD2) are presented. Samples from 9 participants from whom paired samples were available are shown; fold change of mean titers between the 2 time-points are indicated. (C) pNT50 values against the 4 SARS-CoV-2 pseudoviral variants were measured in samples collected after 2 doses of mRNA vaccine. Fold reduction of mean pNT50 compared to D614 are indicated for each variant. (D) Ratios of pNT50 values of the indicated variants of concern over D614 pNT50 are shown. Horizontal bars in (C and D) indicate median values. p values in (C and D) were calculated using repeated measures one way-ANOVA with Geisser Greenhouse correction and with Tukey’s multiple comparisons test. *P < 0.05, **P < 0.01, ****P < 0.0001.
Fig. 2. Plasma neutralizing titers against variants of concern increase after mRNA vaccination in a cohort of pregnant women. (A) Samples collected from a cohort of vaccinated pregnant women at baseline (n=9) and after 2 doses of mRNA vaccine (n=33) were assessed for neutralizing antibody against 4 SARS-CoV-2 pseudovirus strains. (B) pNT50 values of paired samples at baseline and after 2 doses of mRNA vaccine (PD2) are presented. Samples from 9 participants from whom paired samples were available are shown; fold change of mean titers between the 2 time-points are indicated. (C) pNT50 values against the 4 SARS-CoV-2 pseudoviral variants were measured in samples collected after 2 doses of mRNA vaccine. Fold reduction of mean pNT50 compared to D614 are indicated for each variant. (D) Ratios of pNT50 values of the indicated variants of concern over D614 pNT50 are shown. Horizontal bars in (C and D) indicate median values. p values in (C and D) were calculated using repeated measures one way-ANOVA with Geisser Greenhouse correction and with Tukey’s multiple comparisons test. *P < 0.05, **P < 0.01, ****P < 0.0001.CC BY · PubMed Central
Fig. 3. Plasma neutralizing titers against variants of concern are increased after a third dose of mRNA vaccine in a cohort of healthcare workers. (A) Samples were collected from a cohort of healthcare workers who received 2 doses of Pfizer vaccine 21 days apart and received a 3rd dose 242 to 324 days after the first dose. Antibody titers were assessed at 28 and 210 days post dose 1 (PD1), and 7 days and 21 to 28 days post dose 3 (PD3). (B) The kinetics of pNT50 values against D614, Delta, Beta, and Omicron are shown. Dotted lines indicate baseline mean pNT50 obtained from seronegative subjects. Solid lines connect samples from the same participant (C) pNT50 values (left panel) and ratios of pNT50 of the indicated variants of concern over D614 pNT50 (right panel) are shown for samples collected 7 days after 3rd dose of vaccine. (D) pNT50 values (left panel) and ratios of pNT50 of the indicated variants of concern over D614 pNT50 (right panel) are shown for samples collected 21 to 28 days after 3rd dose of vaccine. Horizontal bars in (C and D) indicate median values. p values in (C) were calculated using repeated measures one way-ANOVA with Geisser Greenhouse correction and with Tukey’s multiple comparisons test. p values in (B and D) were calculated using mixed effects analysis with Geisser-Greenhouse correction and Tukey’s multiple comparisons test. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.
Fig. 3. Plasma neutralizing titers against variants of concern are increased after a third dose of mRNA vaccine in a cohort of healthcare workers. (A) Samples were collected from a cohort of healthcare workers who received 2 doses of Pfizer vaccine 21 days apart and received a 3rd dose 242 to 324 days after the first dose. Antibody titers were assessed at 28 and 210 days post dose 1 (PD1), and 7 days and 21 to 28 days post dose 3 (PD3). (B) The kinetics of pNT50 values against D614, Delta, Beta, and Omicron are shown. Dotted lines indicate baseline mean pNT50 obtained from seronegative subjects. Solid lines connect samples from the same participant (C) pNT50 values (left panel) and ratios of pNT50 of the indicated variants of concern over D614 pNT50 (right panel) are shown for samples collected 7 days after 3rd dose of vaccine. (D) pNT50 values (left panel) and ratios of pNT50 of the indicated variants of concern over D614 pNT50 (right panel) are shown for samples collected 21 to 28 days after 3rd dose of vaccine. Horizontal bars in (C and D) indicate median values. p values in (C) were calculated using repeated measures one way-ANOVA with Geisser Greenhouse correction and with Tukey’s multiple comparisons test. p values in (B and D) were calculated using mixed effects analysis with Geisser-Greenhouse correction and Tukey’s multiple comparisons test. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.CC BY · PubMed Central

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Metadata

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
Venue
Science Translational Medicine
Publisher
American Association for the Advancement of Science (AAAS)
Published
2022-03-02
Volume
14
Issue
634
Pages
eabn7842-eabn7842
ISSN
  • 1946-6234 (ISSN-L)
  • 1946-6242
DOI
10.1126/scitranslmed.abn7842
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
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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