Immune Responses to SARS-CoV-2 Vaccination in Older Adults

Older adults exhibit distinct alterations in both humoral and cellular immunity following SARS-CoV-2 vaccination, driven by immunosenescence and chronic low-grade inflammation. Age-related shrinkage of the naïve T-cell pool and impaired B-cell function lead to lower titres of binding and neutralising antibodies, reduced frequency and polyfunctionality of spike-specific CD4+ and CD8+ T cells, and attenuated germinal centre reactions. Booster doses improve antibody levels and T-cell memory but often fail to match younger cohorts in magnitude or durability, especially against immune-evasive variants. Monitoring antibody correlates of protection, optimising vaccine platforms and intervals, and tailoring adjuvanted formulations are key strategies. Globally, enhancing vaccine efficacy in this demographic remains critical for reducing morbidity and mortality in the face of evolving viral threats.

Research from Nature Portfolio

Impaired CD4+ T-cell responses in adults aged ≥65 years have been linked to lower peak IgG titres and fewer systemic adverse events after two mRNA doses. Older individuals generate fewer CXCR3+ follicular helper and TH1 cells after the first dose, and these cells express higher PD-1, dampening subsequent CD8+ T-cell activation and overall immunogenicity. In a geographically isolated population, adults over 60 maintained protective plasma spike-specific antibody levels (96–98%) up to eleven months post-primary series, alongside robust T-cell memory; however, those aged ≥60 showed a 21% reduction in antibody magnitude. Foundational analysis of BNT162b2 recipients above eighty years revealed diminished neutralisation potency and memory B-cell diversity after the first dose, but full two-dose regimens restored cross-neutralisation against several variants and elicited CD4+ T-cell interferon-γ and interleukin-2 production, underscoring the importance of complete schedules to overcome age-related deficits.

Immune Responses to SARS-CoV-2 Vaccination in Older Adults publication trend

The graph below shows the total number of articles in immune responses to sars-cov-2 vaccination in older adults across all publications each year (not limited to Nature Index journals).

Technical terms

Neutralising antibody: an antibody that binds viral particles to prevent entry into host cells.

Spike glycoprotein: the SARS-CoV-2 surface protein responsible for receptor binding and membrane fusion.

CD4+ T cell: helper T lymphocyte that coordinates adaptive immune responses and cytokine secretion.

Follicular helper T cell (Tfh): a CD4+ subset that supports B-cell maturation and high-affinity antibody production in germinal centres.

Programmed cell death protein 1 (PD-1): an inhibitory receptor on T cells that limits their activation.

Immunosenescence: age-associated decline in immune function characterised by reduced naïve lymphocytes and impaired responses to new antigens.

Seroconversion: the development of detectable specific antibodies in the circulation following infection or vaccination.

Receptor-binding domain (RBD): the region of the spike protein that engages the host ACE2 receptor to initiate infection.

References

1. Impaired CD4+ T cell response in older adults is associated with reduced immunogenicity and reactogenicity of mRNA COVID-19 vaccination. Nature Aging (2023).
2. Robust immune response to COVID-19 vaccination in the island population of Greenland. Communications Medicine (2024).
3. mRNA vaccination in people over 80 years of age induces strong humoral immune responses against SARS-CoV-2 with cross neutralization of P.1 Brazilian variant. eLife (2021).
4. Vaccine-induced correlate of protection against fatal COVID-19 in older and frail adults during waves of neutralization-resistant variants of concern: an observational study. The Lancet Regional Health - Europe (2023).
5. Safety, immunogenicity and protective effect of sequential vaccination with inactivated and recombinant protein COVID-19 vaccine in the elderly: a prospective longitudinal study. Signal Transduction and Targeted Therapy (2024).
6. Reduced Magnitude and Durability of Humoral Immune Responses to COVID-19 mRNA Vaccines Among Older Adults. The Journal of Infectious Diseases (2021).