Reduced Antibody and Cellular Immune Responses Following Dual COVID-19 Vaccination Within Infection-Naïve Residents of Long-Term Care Facilities

Background: Age and frailty are risk factors for poor clinical outcomes following SARS-CoV-2 infection. As such, COVID-19 vaccination has been prioritised for this group but there is concern that immune responses may be impaired due to immune senescence and co-morbidity.Methods: We studied antibody and cellular immune responses following COVID-19 vaccination in 202 staff and 286 residents of long-term care facilities (LTCF). Due to the high prevalence of previous infection within this environment 50% and 51% of these two groups respectively had serological evidence of prior natural SARS-CoV-2 infection.Results: In both staff and residents with previous infection the antibody responses following dual vaccination were strong and equivalent across the age course. In contrast, within infection-naïve donors these responses were reduced by 2.4-fold and 8.1-fold respectively such that values within the resident population were 2.6-fold lower than in staff. Impaired neutralisation of delta variant spike binding was also apparent within donors without prior infection. Spike-specific T cell responses were also markedly enhanced by prior infection and within infection-naive donors were 52% lower within residents compared to staff. Post-vaccine spike-specific CD4+ T cell responses displayed single or dual production of IFN-γ+ and IL-2+ whilst previous infection primed for an extended functional profile with TNF-ɑ+ and CXCL10 production.Interpretation: These data reveal suboptimal post-vaccine immune responses within infection-naïve elderly residents of LTCF and indicate the need for further optimization of immune protection through the use of booster vaccination. 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 nothing to declare.Ethics Approval Statement: Ethical approval for this study was obtained from the South Central - Hampshire B Research Ethics Committee, REC Ref: 20/SC/0238.