Third-dose coronavirus disease 2019 vaccines are being deployed widely but their efficacy has not been assessed adequately in vulnerable older people who exhibit suboptimal responses after primary vaccination series. This observational study, which was carried out by the VIVALDI study based in England, looked at spike-specific immune responses in 341 staff and residents in long-term care facilities who received an mRNA vaccine following dual primary series vaccination with BNT162b2 or ChAdOx1. Third-dose vaccination strongly increased antibody responses with preferential relative enhancement in older people and was required to elicit neutralization of Omicron. Cellular immune responses were also enhanced with strong cross-reactive recognition of Omicron. However, antibody titers fell 21–78% within 100 d after vaccine and 27% of participants developed a breakthrough Omicron infection. These findings reveal strong immunogenicity of a third vaccine in one of the most vulnerable population groups and endorse an approach for widespread delivery across this population. Ongoing assessment will be required to determine the stability of immune protection.
Bibliographical noteFunding Information: The authors would like to thank the staff and residents in the LTCFs that participated in this study, and Mark Marshall at NHS England who pseudonymised the electronic health records. This research was funded in whole, or in part, by the Wellcome Trust [CC2230, CC2087]. For the purpose of Open Access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. This work was supported by the Francis Crick Institute which receives its core funding from Cancer Research UK (CC2230, CC2087), the UK Medical Research Council (CC2230, CC2087), and the Wellcome Trust (CC2230, CC2087); and the Department of Health and Social Care. This report is independent research funded by the Department of Health and Social Care (COVID-19 surveillance studies). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. We thank Prof. Wendy Barclay of Imperial College and the wider Genotype to Phenotype consortium for the Delta strain used in this study, and Max Whiteley and Thushan I de Silva at The University of Sheffield and Sheffield Teaching Hospitals NHS Foundation Trust for providing source material. We thank Prof. Gavin Screaton of the University of Oxford for the Omicron strain used in this study.
L.S. reports grants from the Department of Health and Social Care during the conduct of the study and is a member of the Social Care Working Group, which reports to the Scientific Advisory Group for Emergencies. A.H. is a member of the New and Emerging Respiratory Virus Threats Advisory Group at the Department of Health. The remaining authors declare no competing interests
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Citation: Tut, G., Lancaster, T., Krutikov, M. et al. Strong peak immunogenicity but rapid antibody waning following third vaccine dose in older residents of care homes. Nat Aging 3, 93–104 (2023). https://doi.org/10.1038/s43587-022-00328-3