A booster dose enhances immunogenicity of the COVID-19 vaccine candidate ChAdOx1 nCoV-19 in aged mice
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Abstract
BACKGROUND: The spread of SARS-CoV-2 has caused a worldwide pandemic that has affected almost every aspect of human life. The development of an effective COVID-19 vaccine could limit the morbidity and mortality caused by infection and may enable the relaxation of social-distancing measures. Age is one of the most significant risk factors for poor health outcomes after SARS-CoV-2 infection; therefore, it is desirable that any new vaccine candidates elicit a robust immune response in older adults. METHODS: Here, we use in-depth immunophenotyping to characterize the innate and adaptive immune response induced upon intramuscular administration of the adenoviral vectored ChAdOx1 nCoV-19 (AZD-1222) COVID-19 vaccine candidate in mice. FINDINGS: T cells. and granzyme-B-producing CD8 effectors. Spike-specific IgG and IgM are generated from both the early extrafollicular antibody response and the T follicular helper cell-supported germinal center reaction, which is associated with the production of virus-neutralizing antibodies. A single dose of this vaccine generated a similar type of immune response in aged mice but of a reduced magnitude than in younger mice. We report that a second dose enhances the immune response to this vaccine in aged mice. CONCLUSIONS: This study shows that ChAdOx1 nCoV-19 induces both cellular and humoral immunity in adult and aged mice and suggests a prime-boost strategy is a rational approach to enhance immunogenicity in older persons. FUNDING: This study was supported by BBSRC, Lister institute of Preventative Medicine, EPSRC VaxHub, and Innovate UK.
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Responses to the ChAdOx1 nCov-19 (AZD-1222) vaccine were lower in older than in younger mice, and the difference was overcome by booster dosing.
“These data reflect the finding that responses to the ChAdOx1 nCov-19 (AZD-1222) vaccine were lower in older than in younger mice, and the difference was overcome by booster dosing 21 .”
From Age-related immune response heterogeneity to SARS-CoV-2 vaccine BNT162b2 (2021) · cites this paper as [21]
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- Authors
- Silva-Cayetano, A., Foster, W. S., Innocentin, S., Belij-Rammerstorfer, S., Spencer, A. J., Burton, O. T., Fra-Bidó, S., Le Lee, J., Thakur, N., Conceicao, C., Wright, D., Barrett, J., Evans-Bailey, N., Noble, C., Bailey, D., Liston, A., Gilbert, S. C., Lambe, T., & Linterman, M. A.
- Affiliations
- Babraham Institute (GB)
- University of Oxford (GB)
- The Pirbright Institute (GB)
- Corresponding author
- Lambe, Teresa
- Linterman, Michelle A.
- ORCID
- Venue
- Med
- Publisher
- Elsevier BV
- Published
- 2021-03
- Volume
- 2
- Issue
- 3
- Pages
- 243-262.e8
- ISSN
- 2666-6340 (ISSN-L)
- PMC
- PMC7833318
- OpenAlex
- W3112962014
- Cited by
- 84
- References
- 60
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 9 · 2023: 16 · 2022: 27 · 2021: 23
- FWCI
- 2.17
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Med (publishedVersion, cc-by-nc-nd)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Lirias (KU Leuven) (submittedVersion, cc-by-nc-nd)
- Apollo (University of Cambridge) (submittedVersion, cc-by-nc-nd)
- Apollo
- Funders
- Innovate UK (971615)
- Engineering and Physical Sciences Research Council (EP/RO13756/1)
- Biotechnology and Biological Sciences Research Council (BBS/E/B/000C0428, BBS/E/B/000C0427)
- Babraham Institute
- Lister Institute of Preventive Medicine
- Agency for Science, Technology and Research
- European Molecular Biology Organization
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- COVID-19 vaccines, ChAdOx1 nCoV-19 vaccine, AZD1222, booster vaccination, immunosenescence, aged mice, SARS-CoV-2, adenovirus vector vaccine, T follicular helper cells, germinal center, virus-neutralizing antibodies, CD8+ T cells, granzyme B, humoral immunity, cell-mediated immunity, prime-boost strategy
- MeSH terms
- COVID-19, SARS-CoV-2, COVID-19 Vaccines, ChAdOx1 nCoV-19, Aged, Aged, 80 and over, Animals, Humans, CD8-Positive T-Lymphocytes, Mice
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