RESUMEN
The rapid mutation of SARS-CoV-2 has led to multiple rounds of large-scale breakthrough infection and reinfection worldwide. However, the dynamic changes of humoral and cellular immunity responses to several subvariants after infection remain unclear. In our study, a 6-month longitudinal immune response evaluation was conducted on 118 sera and 50 PBMC samples from 49 healthy individuals who experienced BA.5/BF.7/XBB breakthrough infection or BA.5/BF.7-XBB reinfection. By studying antibody response, memory B cell, and IFN-γ secreting CD4+/CD8+ T cell response to several SARS-CoV-2 variants, we observed that each component of immune response exhibited distinct kinetics. Either BA.5/BF.7/XBB breakthrough infection or BA.5/BF.7-XBB reinfection induces relatively high level of binding and neutralizing antibody titers against Omicron subvariants at an early time point, which rapidly decreases over time. Most of the individuals at 6 months post-breakthrough infection completely lost their neutralizing activities against BQ.1.1, CH.1.1, BA.2.86, JN.1 and XBB subvariants. Individuals with BA.5/BF.7-XBB reinfection exhibit immune imprinting shifting and recall pre-existing BA.5/BF.7 neutralization antibodies. In the BA.5 breakthrough infection group, the frequency of BA.5 and XBB.1.16-RBD specific memory B cells, resting memory B cells, and intermediate memory B cells gradually increased over time. On the other hand, the frequency of IFN-γ secreting CD4+/CD8+ T cells induced by WT/BA.5/XBB.1.16 spike trimer remains stable over time. Overall, our research indicates that individuals with breakthrough infection have rapidly declining antibody levels but have a relatively stable cellular immunity that can provide some degree of protection from future exposure to new antigens.
RESUMEN
Emerging SARS-CoV-2 sub-lineages like XBB.1.5, XBB.1.16, EG.5, HK.3 (FLip), and XBB.2.3 and the variant BA.2.86 have recently been identified. Understanding the efficacy of current vaccines on these emerging variants is critical. We evaluate the serum neutralization activities of participants who received COVID-19 inactivated vaccine (CoronaVac), those who received the recently approved tetravalent protein vaccine (SCTV01E), or those who had contracted a breakthrough infection with BA.5/BF.7/XBB virus. Neutralization profiles against a broad panel of 30 sub-lineages reveal that BQ.1.1, CH.1.1, and all the XBB sub-lineages exhibit heightened resistance to neutralization compared to previous variants. However, despite their extra mutations, BA.2.86 and the emerging XBB sub-lineages do not demonstrate significantly increased resistance to neutralization over XBB.1.5. Encouragingly, the SCTV01E booster consistently induces higher neutralizing titers against all these variants than breakthrough infection does. Cellular immunity assays also show that the SCTV01E booster elicits a higher frequency of virus-specific memory B cells. Our findings support the development of multivalent vaccines to combat future variants.
