Informing the Value of “Boosting” Immunocompetent Adults based on Immune Responses Among US Service Members to SARS-CoV-2 Variants in Late 2024

Background: COVID-19 remains a global biothreat because of new immune-evasive SARS-CoV-2 variants, heterogeneous immunity, and evolving vaccine recommendations. Methods: In this cross-sectional study conducted in September 2024, we evaluated the adaptive immune responses in immunocompetent US active-duty personnel who completed a COVID-19 primary vaccine series but had variable subsequent vaccination and infection histories. We compared responses to 4 circulating variants (JN.1, KP.2, KP.3, LB.1) versus 2 previous dominant vaccine variants (BA.5, XBB.1.5). Analyses were performed based on timing (within or beyond 12 months from enrollment) and type of the most recent exposure, defined as either a COVID-19 vaccination or natural infection. Results: T cells against circulating variants compared to previous variants. The reduction in humoral responses was more pronounced in those whose most recent exposure was greater than 12 months from enrollment. In contrast, cell-mediated T-cell responses were largely consistent regardless of the timing of the most recent exposure. The type of most recent exposure was not a significant factor in determining the magnitude of current immune responses. Conclusions: Administration of COVID-19 boosters is likely to enhance cross-reactive humoral responses against SARS-CoV-2 circulating variants, potentially facilitating protection from infection and fewer missed work days among military populations. Ongoing surveillance is needed to inform future vaccine composition, timing of administration, and targeted populations to maximize protective benefits.