ABSTRACT
Whether age-associated defects in T cells impact the immunogenicity and reactogenicity of mRNA vaccines remains unclear. Using a vaccinated cohort (n = 216), we demonstrated that older adults (aged ≥65 years) had fewer vaccine-induced spike-specific CD4+ T cells including CXCR3+ circulating follicular helper T cells and the TH1 subset of helper T cells after the first dose, which correlated with their lower peak IgG levels and fewer systemic adverse effects after the second dose, compared with younger adults. Moreover, spike-specific TH1 cells in older adults expressed higher levels of programmed cell death protein 1, a negative regulator of T cell activation, which was associated with low spike-specific CD8+ T cell responses. Thus, an inefficient CD4+ T cell response after the first dose may reduce the production of helper T cytokines, even after the second dose, thereby lowering humoral and cellular immunity and reducing systemic reactogenicity. Therefore, enhancing CD4+ T cell response following the first dose is key to improving vaccine efficacy in older adults.
Subject(s)
COVID-19 Vaccines , COVID-19 , Humans , Aged , COVID-19 Vaccines/adverse effects , COVID-19/prevention & control , Vaccination/adverse effects , Immunity, Cellular , CD4-Positive T-LymphocytesABSTRACT
Age is a major risk factor for COVID-19 severity, and T cells play a central role in anti-SARS-CoV-2 immunity. Because SARS-CoV-2-cross-reactive T cells have been detected in unexposed individuals, we investigated the age-related differences in pre-existing SARS-CoV-2-reactive T cells. SARS-CoV-2-reactive CD4+ T cells from young and elderly individuals were mainly detected in the central memory fraction and exhibited similar functionalities and numbers. Naïve-phenotype SARS-CoV-2-reactive CD8+ T cell populations decreased markedly in the elderly, while those with terminally differentiated and senescent phenotypes increased. Furthermore, senescent SARS-CoV-2-reactive CD8+ T cell populations were higher in cytomegalovirus seropositive young individuals compared to seronegative ones. Our findings suggest that age-related differences in pre-existing SARS-CoV-2-reactive CD8+ T cells may explain the poor outcomes in elderly patients and that cytomegalovirus infection is a potential factor affecting CD8+ T cell immunity against SARS-CoV-2. Thus, this study provides insights for developing effective therapeutic and vaccination strategies for the elderly.
ABSTRACT
Condition:
COVID-19Primary outcome:
1) Anti-Ig levels in blood2) T-cell response in peripheral blood
3) Phenotypes of immune cells in peripheral blood
Criteria:
Inclusion criteria: 1) Subjects working at Kyoto University and aged 20 years old or older at informed consent with no major medical history and other medical problems2) Subjects aged 65 years old or older at informed consent with no major medical history
3) Subjects who have obtained written consent voluntarily to participate in this trial
4) Subjects who are scheduled to receive COVID-19 vaccination
Exclusion criteria: 1) Subjects who have been administered with drugs that affect the immune system (excluding external preparations) such as immunomodulators (DMARDs, etc.), immunosuppressants, biologics, etc.
2) Subjects who are tested positive for human immunodeficiency virus (HIV), hepatitis C virus (HCV), hepatitis B virus (HBV), or HTLV-1.
3) Subjects who are otherwise ineligible for this study in the principal investigator's or subinvestigator's opinion.