ABSTRACT
COVID-19 remains a global public health challenge due to ongoing emergence of new immune-evasive SARS-CoV-2 variants, heterogeneous immunity, poor education campaigns, and suboptimal surveillance. In this cross-sectional study, we evaluated the adaptive immune responses in US active-duty service members who completed a COVID-19 primary vaccine series to 3 previously dominant variants (Ancestral, Delta, BA.5) and compared them to 3 variants currently circulating (XBB.1.5, EG.5, and BA.2.86). Analyses were performed based upon time (within or beyond 12 months) and type (vaccine or infection) of most recent exposure. Significant reduction was observed in binding antibodies, neutralization antibodies, memory B cells, and CD8+ T cells against current circulating variants compared to previous dominant variants. The reduction in antibody response was more pronounced in those whose most recent exposure, regardless if vaccination or infection, was greater than 12 months from study enrollment. In contrast, the CD4+ T cell response was largely consistent across all tested variants. Our study did not show that the type exposure in the last 12 months was a significant factor in determining the magnitude of immune responses. However, the antibody responses to circulating variants were decreased among participants who received the bivalent booster compared to those with an infection in the past 12 months, potentially due to immunological imprinting of the Ancestral strain. Administration of the new XBB.1.5-based booster is likely to enhance cross-reactive humoral immune responses against current SARS-CoV-2 circulating strains.