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Front Immunol. 2025;16:1579163. doi: 10.3389\/fimmu.2025.1579163. eCollection 2025.<\/p>\n
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Torre D, Orlandi C, Conti I, Barocci S, Carlotti E, Magnani M, Casabianca A, Stefanetti G.<\/p>\n
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To address the COVID-19 pandemic, diverse vaccination strategies, including homologous and heterologous schedules, were employed to enhance immune protection. This study evaluates the long-term humoral and cellular immune responses in individuals vaccinated with homologous (ChAdOx1-S\/ChAdOx1-S [ChAd\/ChAd]) and heterologous (ChAdOx1-S\/BNT162b2 [ChAd\/BNT]) schedules, followed by a third-dose mRNA booster (BNT162b2 [BNT] or mRNA-1273). Anti-Spike IgG titers were measured at 9-, 12-, and 21-months post-primary vaccination (corresponding to 3-, 6-, and 15-months post-booster), while SARS-CoV-2-specific B- and T-cell responses were assessed at 21-months post-booster. Antibody titers declined by 12-
months post-primary vaccination, regardless of the third dose administered, and increased significantly by 21-months, potentially due to a fourth dose (BNT or mRNA-1273) or natural SARS-CoV-2 infection. The heterologous ChAd\/BNT schedule elicited a stronger and more durable immune response than the homologous ChAd\/ChAd, as evidenced by higher anti-Spike IgG titers, increased IgM-\/IgG+ memory B-cell activation, and enhanced cytotoxic CD8+ T-cell cytokine expression in infected individuals. SARS-CoV-2 infection further boosted humoral and cellular responses, with infected individuals showing higher anti-Spike IgG titers and greater CD8+ T-cell activation compared to uninfected individuals. These findings highlight the benefits of heterologous vaccination schedules and the role of infection-driven immune activation, providing valuable insights for optimizing vaccination strategies to improve long-term immunity against SARS-CoV-2.<\/p>\n
Copyright \u00a9 2025 Torre, Orlandi, Conti, Barocci, Carlotti, Magnani, Casabianca and Stefanetti.
DOI: 10.3389\/fimmu.2025.1579163
PMCID: PMC12081374
PMID: 40386778 [Indexed for MEDLINE]<\/p>\n
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