Abstract

Abstract The emergence of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) Omicron subvariants raises concerns regarding the effectiveness of immunity acquired from previous Omicron subvariants breakthrough infections (BTIs) or reinfections (RIs) against the current circulating Omicron subvariants. In this study, we prospectively investigate the dynamic changes of virus‐specific antibody and T cell responses among 77 adolescents following Omicron BA.2.3 BTI with or without subsequent Omicron BA.5 RI. Notably, the neutralizing antibodies (NAbs) titers against various detected SARS‐CoV‐2 variants, especially the emerging Omicron CH.1.1, XBB.1.5, XBB.1.16, EG.5.1, and JN.1 subvariants, exhibited a significant decrease along the time. A lower level of IgG and NAbs titers post‐BTI was found to be closely associated with subsequent RI. Elevated NAbs levels and shortened antigenic distances were observed following Omicron BA.5 RI. Robust T cell responses against both Omicron BA.2‐ and CH.1.1‐spike peptides were observed at each point visited. The exposure to Omicron BA.5 promoted phenotypic differentiation of virus‐specific memory T cells, even among the non‐seroconversion adolescents. Therefore, updated vaccines are needed to provide effective protection against newly emerging SARS‐CoV‐2 variants among adolescents.