Delayed-interval BNT162b2 mRNA COVID-19 vaccination enhances humoral immunity and induces robust T cell responses
Open accessPublished version of a preprint
Abstract
Delayed dosing intervals are a strategy to immunize a greater proportion of the population. In an observational study, we compared humoral and cellular responses in health care workers receiving two doses of BNT162b2 (Pfizer-BioNTech) vaccine at standard (3- to 6-week) and delayed (8- to 16-week) intervals. In the delayed-interval group, anti-receptor-binding domain antibody titers were significantly enhanced compared to the standard-interval group. The 50% plaque reduction neutralization test (PRNT50) and PRNT90 titers against wild-type (ancestral) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and Alpha, Beta and Delta variants were higher in the delayed-interval group. Spike-specific polyfunctional CD4+ and CD8+ T cells expressing interferon-γ and interleukin-2 were comparable between the two groups. Here, we show that the strategy of delaying second doses of mRNA vaccination may lead to enhanced humoral immune responses, including improved virus neutralization against wild-type and variant SARS-CoV-2 viruses. This finding has potentially important implications as vaccine implementation continues across a greater proportion of the global population.
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A growing number of studies suggest that an extended dosing interval amplifies both the humoral immune response and perhaps the cellular response, and is an effective global strategy given discrepancies between regions with high and low vaccination coverage.
“Nonetheless, a growing number of studies suggest that an extended dosing interval amplifies both the humoral immune response30 and perhaps the cellular response,31 and is an effective global strategy given the discrepancies between regions with high and low vaccination coverage.32”
Recent studies have so far only investigated the second dose and have not evaluated responses to the omicron variant.
“But even recent studies have so far only investigated the second dose and have not evaluated responses to the omicron variant.30 33”
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References 18 · Cited by 114
Research works printed but not linked: 2
- Macallan, D. C., Borghans, J. A. & Asquith, B. Human T cell memory: a dynamic view. Vaccines (Basel) 5, 877 (2017).
- Valcourt, E. J. et al. Evaluating humoral immunity against SARS-CoV-2: validation of a plaque-reduction neutralization test and a multilaboratory comparison of conventional and surrogate neutralization assays. Microbiol. Spectr. 9, e0088621 (2021).
- Authors
- Hall, V. G., Ferreira, V. H., Wood, H., Ierullo, M., Majchrzak-Kita, B., Manguiat, K., Robinson, A., Kulasingam, V., Humar, A., & Kumar, D.
- Affiliations
- University Health Network (CA)
- Public Health Agency of Canada (CA)
- Corresponding author
- Hall, Victoria G.
- Kumar, Deepali
- ORCID
- Venue
- Nature Immunology
- Published
- 2022-02-03
- Volume
- 23
- Issue
- 3
- Pages
- 380-385
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- OpenAlex
- W4210343424
- Cited by
- 114
- References
- 18
- Citations by year
- 2026: 5 · 2025: 15 · 2024: 27 · 2023: 27 · 2022: 38 · 2021: 2
- FWCI
- 13.11
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Nature Immunology (publishedVersion)
- Research Square (acceptedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Public Health Agency of Canada
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Social Sciences › Health › Vaccine Coverage and Hesitancy
- Keywords
- BNT162b2 mRNA vaccine, COVID-19 vaccination, humoral immune response, T cell response, neutralizing antibodies, SARS-CoV-2 variants, healthcare workers, vaccination coverage
- MeSH terms
- COVID-19, SARS-CoV-2, Vaccination Hesitancy, BNT162 Vaccine, Adult, Cells, Cultured, Female, Humans, Immunization, Secondary, Interferon-gamma, Interleukin-2, Male, Middle Aged, Vaccination, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Immunity, Humoral
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