Neutralizing antibody activity against 21 SARS-CoV-2 variants in older adults vaccinated with BNT162b2
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Abstract
SARS-CoV-2 variants may threaten the effectiveness of vaccines and antivirals to mitigate serious COVID-19 disease. This is of most concern in clinically vulnerable groups such as older adults. We analysed 72 sera samples from 37 individuals, aged 70–89 years, vaccinated with two doses of BNT162b2 (Pfizer–BioNTech) 3 weeks apart, for neutralizing antibody responses to wildtype SARS-CoV-2. Between 3 and 20 weeks after the second vaccine dose, neutralizing antibody titres fell 4.9-fold to a median titre of 21.3 (neutralization dose 80%), with 21.6% of individuals having no detectable neutralizing antibodies at the later time point. Next, we examined neutralization of 21 distinct SARS-CoV-2 variant spike proteins with these sera, and confirmed substantial antigenic escape, especially for the Omicron (B.1.1.529, BA.1/BA.2), Beta (B.1.351), Delta (B.1.617.2), Theta (P.3), C.1.2 and B.1.638 spike variants. By combining pseudotype neutralization with specific receptor-binding domain (RBD) enzyme-linked immunosorbent assays, we showed that changes to position 484 in the spike RBD were mainly responsible for SARS-CoV-2 neutralizing antibody escape. Nineteen sera from the same individuals boosted with a third dose of BNT162b2 contained higher neutralizing antibody titres, providing cross-protection against Omicron BA.1 and BA.2. Despite SARS-CoV-2 immunity waning over time in older adults, booster vaccines can elicit broad neutralizing antibodies against a large number of SARS-CoV-2 variants in this clinically vulnerable cohort.
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The decrease in protection against Delta has been mainly attributed to a decay of vaccine-induced neutralizing antibodies over time rather than an intrinsic capacity of the Delta variant to escape immunity.
“The decrease in protection against Delta has been mainly attributed to a decay of vaccine-induced neutralizing antibodies over time rather than an intrinsic capacity of the Delta variant to escape immunity [27,28].”
From Vaccine effectiveness and duration of protection of COVID-19 mRNA vaccines against Delta and Omicron BA.1 symptomatic and severe COVID-19 outcomes in adults aged 50 years and over in France (2023) · cites this paper as [28]
In the section on variant neutralization (page unavailable), Delta neutralization was already 9.0- to 11.2-fold lower than B.1 at three weeks after vaccination; Delta titres were only slightly lower at 20 weeks. The Discussion says reduced neutralization of Delta was compounded by waning immunity, not mainly caused by waning rather than variant-specific escape. The study does not establish the cause of a decrease in clinical protection. (LLM, conf=0.87)
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SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway
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“The decrease in protection against Delta has been mainly attributed to a decay of vaccine-induced neutralizing antibodies over time rather than an intrinsic capacity of the Delta variant to escape immunity [27,28].”
- Authors
- Newman, J., Thakur, N., Peacock, T. P., Bialy, D., Elrefaey, A. M. E., Bogaardt, C., Horton, D. L., Ho, S., Kankeyan, T., Carr, C., Hoschler, K., Barclay, W. S., Amirthalingam, G., Brown, K. E., Charleston, B., & Bailey, D.
- Affiliations
- The Pirbright Institute (GB)
- UK Health Security Agency (GB)
- University of Surrey (GB)
- Corresponding author
- Bailey, Dalan
- ORCID
- Venue
- Nature Microbiology
- Published
- 2022-07-14
- Volume
- 7
- Issue
- 8
- Pages
- 1180-1188
- ISSN
- 2058-5276 (ISSN-L)
- PMC
- PMC9352594
- OpenAlex
- W4285386858
- Cited by
- 85
- References
- 15
- Citations by year
- 2026: 5 · 2025: 14 · 2024: 20 · 2023: 27 · 2022: 19
- FWCI
- 9.76
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Nature Microbiology (publishedVersion, cc-by)
- medRxiv (acceptedVersion)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- RCUK | Biotechnology and Biological Sciences Research Council (BB/T008784/1, BBS/E/I/COV07001, BBS/E/I/00007031, BBS/E/I/00007038, BBS/E/I/00007039, BBS/E/I/00007034)
- RCUK | Medical Research Council (MR/W005611/1)
- EC | Horizon 2020 Framework Programme (773830)
- 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 variants, neutralizing antibodies, BNT162b2, older adults, vaccine waning, antigen escape, spike protein receptor-binding domain, booster vaccination, cross-protection, COVID-19 pandemic
- MeSH terms
- COVID-19, SARS-CoV-2, BNT162 Vaccine, Aged, Antibodies, Viral, Humans, Membrane Glycoproteins, Neutralization Tests, Viral Envelope Proteins, Antibodies, Neutralizing
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