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.

Background: The monkeypox virus (MPXV) has raised global health concerns due to its widespread transmission. This study evaluated the MPXV immunogenic antigens and the impact of vaccinia virus (VACV) vaccination and MPXV infection on cross-reactive antibody responses to conserved proteins from representative MPXV strains that reflected the evolutionary trajectory. Methods: Phylogenetic analyses were first conducted to reveal the evolutionary trajectory of MPXV from 1970 to 2024. A total of 84 serum samples were collected: 42 from VACV-vaccinated individuals, 12 from MPXV-infected participants in the early stage, 13 from the late stage, and 17 from naive individuals. Demographic data, MPXV and HIV status, as well as other clinical information were collected using standardized forms. Immunogenicity, cross-reactive antibody responses, and amino acid similarity to 15 MPXV surface proteins were assessed using enzyme-linked immunosorbent assays, VACV neutralization tests, and sequence alignment. Data analysis methods included analysis of variance, Mann–Whitney U test, binary logistic regression, Pearson correlation, and linear regression, with a significance threshold of P < 0.05. Results: The 186 complete genome sequences were classified into different clades and lineages, ranging from clade Ia to clade IIb C.1.1. Individuals infected with MPXV demonstrated strong antibody responses to antigens A35R, B6R, H3L, and E8L. VACV-vaccinated individuals exhibited broader cross-reactivity, particularly against A21L (P = 0.0003), A28L (P = 0.0028), A29L (P = 0.0324), G2R (P = 0.0003), and H2R (P = 0.0008), compared to MPXV-infected individuals. Pearson correlation analysis revealed significant associations (P = 0.0049) between antibody responses and the amino acid sequence similarity with other orthopoxviruses. Furthermore, MPXV-infected individuals exhibited greater neutralizing activity against VACV than those VACV-vaccinated individuals (P < 0.0001), while the vaccinated group retained cross-protective immunity even decades post-vaccination. Conclusions: A35R, B6R, H3L, and E8L are the main immunogenic antigens of MPXV. VACV-vaccination triggers a cross-reactive antibody response to MPXV surface proteins. Our findings suggest the need for targeted vaccines and antibody treatments for MPXV, as well as the reintroduction of smallpox vaccinations with booster doses for high-risk groups. Graphical

Stevioside is a natural sweetener with the characteristics of low calorie and high sweetness. It comprises a diverse range of monomers that play crucial roles in numerous biological processes. Due to these attributes, it has gained widespread application in agriculture, food, and pharmaceutical industries. As a substitute for sugar, stevioside also shows good pharmacological activities on glucose metabolism, bodyweight keeping, blood pressure maintenance, and shows anti‐inflammatory, anti‐oxidation, anti‐tumor, antibacterial, and immune regulation activities. This review summarized the update on the food safety, sweet structure–activity relationship, pharmacological activity of stevia glycosides recently, and discussed the limitations of its application in food and medicine.