Publication date: Feb 15, 2025

Limited research has explored the immunological effects of a second COVID-19 vaccine booster in older adults within Western Pacific countries. This study involved healthcare workers aged ≥65 years who received two doses of ChAdOx1 nCoV-19 (A), mRNA-1273 (M), or MVC-COV1901 (Mc), followed by a booster dose of mRNA-1273. Younger adults served as controls. Humoral and cellular immune responses were measured before and after the vaccination. Younger adults exhibited the highest fold-rise in anti-spike IgG levels (13. 20, p < 0. 001), followed by the AAMM (9. 93, p < 0. 001), McMcMM (6. 97), and MMMM (4. 9, p < 0. 05) groups. Cellular response increased most in the McMcMM group (3. 77), followed by AAMM (3. 04, p < 0. 001), MMMM (2. 24), and the younger group (1. 08). Neutralizing activity against the D614G variant was highest in younger adults (7. 77, p < 0. 001), followed by AAMM (4. 07, p < 0. 001), MMMM (2. 89, p < 0. 05), and McMcMM (2. 76). Against the XBB. 1.16 variant, titers were significantly lower (17. 33-29. 08 times less than wild type). The highest fold-rise was observed in the McMcMM group (8. 59), followed by AAMM (7. 66, p < 0. 001), MMMM (4. 16), and younger adults (2. 26). A second mRNA COVID-19 booster increased neutralizing antibodies and enhanced T cell responses against SARS-CoV-2 variants. Adapted vaccines targeting new subvariants are critical to strengthen immunity, particularly for older adults facing vaccine-resistant strains.

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