ABSTRACT
The effect of COVID-19 booster vaccination on SARS-CoV-2 T-cell mediated immune responses in elderly nursing home residents has not been explored in depth. Thirty-nine elderly nursing home residents (median age, 91 years) were included, all fully vaccinated with mRNA vaccines. The frequency of and the integrated mean fluorescence (iMFI) for peripheral blood SARS-CoV-2-Spike reactive IFN-γ-producing CD4+ or CD8+ T cells before and after the first (Pre-3D and Post-3D) and second (Pre-4D and Post-4D) vaccine booster doses was determined using flow cytometry for an intracellular staining method. 3D increased significantly (p = 0.01) the percentage of participants displaying detectable SARS-CoV-2-T-cell responses compared with pre-3D (97% vs. 74%). The magnitude of the increase was statistically significant for CD8+ T cells (p = 0.007) but not for CD4+ T cells (p = 0.77). A trend towards higher frequencies of peripheral blood SARS-CoV-2-CD8+ T cells was observed post-3D compared with pre-3D (p = 0.06). The percentage of participants with detectable SARS-S-CoV-2 CD4+ T-cell responses decreased post-4D (p = 0.035). Following 4D, a nonsignificant decrease in the frequencies of both T cell subsets was noticed (p = 0.94 for CD8+ T cells and p = 0.06 for CD4+ T cells). iMFI data mirrored that of T-cell frequencies. The kinetics of SARS-CoV-2 CD8+ and CD4+ T cells following receipt of 3D and 4D were comparable across SARS-CoV-2-experienced and -naïve participants and between individuals receiving a homologous or heterologous vaccine booster. 3D increased the percentage of elderly nursing home residents displaying detectable SARS-CoV-2 T-cell responses but had a marginal effect on T-cell frequencies. The impact of 4D on SARS-CoV-2 T-cell responses was negligible; whether this was due to suboptimal priming or rapid waning could not be ascertained.
Subject(s)
CD4-Positive T-Lymphocytes , CD8-Positive T-Lymphocytes , COVID-19 Vaccines , COVID-19 , Immunization, Secondary , Nursing Homes , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Humans , Aged, 80 and over , Male , Spike Glycoprotein, Coronavirus/immunology , Female , CD8-Positive T-Lymphocytes/immunology , COVID-19/immunology , COVID-19/prevention & control , CD4-Positive T-Lymphocytes/immunology , COVID-19 Vaccines/immunology , COVID-19 Vaccines/administration & dosage , SARS-CoV-2/immunology , Aged , Interferon-gamma , mRNA VaccinesABSTRACT
The immune effector mechanisms involved in protecting against severe COVID-19 infection in elderly nursing home residents following vaccination or natural infection are not well understood. Here, we measured SARS-CoV-2 Spike (S)-directed functional antibody responses, including neutralizing antibodies (NtAb) and antibody Fc-mediated NK cell activity (degranulation and IFNγ production), against the Wuhan-Hu-1, BA.4/5 (for NtAb), and Omicron XBB.1.5 variants in elderly nursing home residents (n = 39; median age, 91 years) before and following a third (pre- and post-3D) and a fourth (pre- and post-4D) mRNA COVID-19 vaccine dose. Both 3D and 4D boosted NtAb levels against both (sub)variants. Likewise, 3D and 4D increased the ability of sera to trigger both LAMP1- and IFNγ-producing NK cells, in particular against XBB.1.5. In contrast to NtAb titres, the frequencies of LAMP1- and IFNγ-producing NK cells activated by antibodies binding to Wuhan-Hu-1 and Omicron XBB.1.5 S were comparable at all testing times. Stronger functional antibody responses were observed in vaccine-experienced participants compared to vaccine-naïve at some testing times. These findings can contribute to identifying a reliable correlate of protection in elderly nursing home residents against severe COVID-19 and inform future vaccine strategies in this population group.