Publication date: Feb 03, 2025

The ongoing COVID-19 pandemic has underscored the importance of strong immune defenses against emerging SARS-CoV-2 variants. While COVID-19 vaccines containing XBB subvariants have proven effective in neutralizing new SARS-CoV-2 variants, a gap remains in knowledge regarding neutralizing antibody responses in older adults aged >65 years against these newly emerged variants. This study was therefore undertaken to investigate and compare neutralizing antibody responses to three XBB-containing protein-based vaccines (trivalent XBB. 1.5 vaccine, bivalent Omicron XBB vaccine, and tetravalent XBB. 1 vaccine) head-to-head in 90 individuals aged >65 years. The results showed that all three XBB-containing vaccines substantially enhanced the neutralizing antibody response, with 100% of vaccinees having detectable antibody titers against ancestral D614G and variants BA. 5, XBB. 1.5, JN. 1, KP. 2, and KP. 3 after booster immunization. Subsequent analysis indicated that the trivalent XBB. 1.5 and tetravalent XBB. 1 vaccines elicited higher levels of neutralizing antibodies compared to the bivalent Omicron XBB vaccine. The KP. 2 and KP. 3 variants displayed antibody resistance comparable to the JN. 1 variant. Older adults produce similar neutralizing antibody responses to the vaccines regardless of their underlying medical conditions. These findings indicate that booster vaccination with XBB-containing vaccines can effectively elicit strong neutralizing responses against a number of SARS-CoV-2 variants in older adults over 65 years, which will help guide vaccine strategies in this elderly population.

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