SARS-CoV-2 vaccine(The Scientific and Technological Research Council of Turkey)

Older adults are highly vulnerable to infectious diseases, and vaccines are often less effective in this population because of diminished B and T cell memory responses driven by impaired autophagy, immunosenescence, and chronic low‐grade inflammation. Spermidine has been shown to counteract immunosenescence and induce autophagy in preclinical models, and its levels decline with age in humans. We conducted a double‐blind, randomised, placebo‐controlled pilot study in 40 adults over 65 years of age following their third SARS‐CoV‐2 vaccine dose to assess the safety of Spermidine and its effects on vaccine‐induced immunity. Daily oral supplementation (6 mg, 13 weeks) was well‐tolerated. Vaccine non‐responsiveness was common, and non‐responders exhibited a distinct immune‐senescence signature marked by elevated p16, mTOR signalling, and γ‐H2AX+ DNA damage in lymphocytes. Spermidine reversed these features and significantly enhanced spike‐specific IgG secretion, memory B cell recall responses and neutralising antibody activity, specifically in non‐responders. Single‐cell RNA‐seq after treatment revealed increased expression of TFEB targets and autophagy‐related genes in B cells, in line with elevated autophagic flux. These findings suggest that targeting immune cell senescence with Spermidine may improve vaccine responsiveness in older adults and highlight immune‐senescence markers as potential predictors of vaccine failure in ageing populations.

High homology and cross-reactive immune responses have been reported between SARS-CoV-2 and seasonal human coronaviruses (HCoVs). However, the impact of preexisting immunity against seasonal HCoVs on SARS-CoV-2 vaccination is undetermined.

We conducted a cross-sectional study involving pediatric and adult participants between August 2020 and August 2023. IgG titers against SARS-CoV-2 and seasonal HCoV-229E, -HKU1, -NL63, and -OC43 were quantified by electrochemiluminescent immunoassay. A paired analysis was performed in a subset of participants with samples collected before and after SARS-CoV-2 vaccination.

A total of 1804 participants were enrolled (median age, 44 years; range, 2–95). IgG titers against HCoV-229E, -HKU1, and -OC43 increased during early childhood. Among participants without prior SARS-CoV-2 infection who were SARS-CoV-2-vaccinated, anti-spike IgG titers against SARS-CoV-2 positively correlated with titers against HCoV-OC43, -HKU1, and -NL63 (Spearman r = 0.40, 0.26, and 0.12, respectively; P < .0001, P < .0001, and P = .0002). In paired analysis, participants with high baseline HCoV-HKU1 and -OC43 IgG titers developed higher postvaccination anti-SARS-CoV-2 spike IgG responses than those with low baseline titers (geometric mean [arbitrary units/mL]: 111 384 vs 54 610 and 113 279 vs 50 099; P = .03 and .015). Multivariable linear regression analyses demonstrated that baseline HCoV-HKU1 and -OC43 IgG titers remained independently associated with postvaccination anti-SARS-CoV-2 spike IgG levels (β = 110 592 and 108 855; 95% CI, 17 922–203 262 and 12 013–205 697; P = .020 and .028).

Higher baseline immunity to HCoV-HKU1 and -OC43 was associated with stronger SARS-CoV-2 vaccine–induced antibody responses. These findings suggest that preexisting immunity against seasonal betacoronaviruses may enhance humoral immune response to SARS-CoV-2 vaccination.