Booster Vaccination Strongly Enhances SARS-CoV-2-Specific Antibody and Cellular Responses in Elderly Residents of Care Homes

Third dose ‘booster’ COVID-19 vaccines can increase SARS-CoV-2 specific immune responses and are being deployed widely to control the impact of omicron variant infection. However, the efficacy of booster vaccines has not been assessed in the most vulnerable demographic groups such as the elderly and frail. This is important as elderly residents in care facilities who have not had a prior natural SARS-CoV-2 infection exhibit suboptimal antibody and cellular responses following dual vaccination. We studied immune responses in 134 staff and residents in long term care facilities (LTCF) who had received an mRNA booster vaccine following initial dual homologous vaccination with either Pfizer mRNA or ChAdOx1 vaccine. Booster vaccination strongly increased antibody responses irrespective of prior infection status. Amongst staff and residents with serological evidence of prior infection these were 4.1-fold and 3.2-fold higher than following dual vaccination. Furthermore, these were increased by 6.4-fold and 12.3-fold within infection-naïve donors such that elderly donors achieved a similar antibody level to younger staff. Cellular immune responses were boosted only in older donors and achieved equivalence across the life course. The immunogenicity of the mRNA booster vaccine was equivalent in donors who had received either mRNA or adenovirus baseline vaccination. As such, booster vaccination can overcome the negative influence of age on immune responses to dual COVID-19 vaccination in the LTCF setting. These findings reveal strong immunogenicity after the 3rd booster vaccine dose in one of the most vulnerable clinical groups and endorse an approach for rapid delivery across this population.Clinical Trial Registration Details: The VIVALDI study (ISRCTN14447421).Funding Information: UK Government Department of Health and Social Care.Declaration of Interests: LS 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. AH is a member of the New and Emerging Respiratory Virus Threats Advisory Group at the Department of Health. All other authors have no interests to declare.Ethics Approval Statement: All participants provided written informed consent for blood sample collection or if residents lacked the capacity to consent, a personal or nominated consultee was identified to act on their behalf. Ethical approval for this study was obtained from the South Central - Hampshire B Research Ethics Committee, REC Ref: 20/SC/0238.