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As long as the coronavirus disease 2019 (COVID-19) pandemic continues, new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with altered antigenicity will emerge. The development of vaccines that elicit robust, broad, and durable protection against SARS-CoV-2 variants is urgently needed. We have developed a vaccine (rDIs-S) consisting of the attenuated vaccinia virus DIs strain platform carrying the SARS-CoV-2 S gene. rDIs-S induced neutralizing antibody and T-lymphocyte responses in cynomolgus macaques and human angiotensin converting enzyme 2 (hACE2) transgenic mice, and showed broad protection against SARS-CoV-2 isolates ranging from the early-pandemic strain (WK-521) to the recent Omicron BA. 1 variant (TY38-839). Using a tandem mass tag (TMT) -based quantitative proteomic analysis of lung homogenates from hACE2 transgenic mice, we found that, among mice subjected to challenge infection with WK-521, vaccination with rDIs-S prevented protein expression related to the severe pathogenic effects of SARS-CoV-2 infection (tissue destruction, inflammation, coagulation, fibrosis, and angiogenesis) and restored protein expression related to immune responses (antigen presentation and cellular response to stress). Furthermore, long-term studies in mice showed that rDIs-S maintains S protein-specific antibody titers for at least 6 months after a 1st vaccination. Thus, rDIs-S appears to provide broad and durable protective immunity against SARS-CoV-2, including current and possibly future variants.

Background AimsIn natural infections with hepatitis B virus (HBV), large amounts of hepatitis B surface-small antigen (HBs-S) subviral particles (SVPs), which do not contain viral nucleocapsid, are secreted into the blood. The function of excess amounts of SVPs remains largely unknown. In this study, we analyzed the function of HBs-S in HBV infection.MethodsThe effect of HBs-S in HBV infection was evaluated in a human hepatoma cell line, in primary human hepatocytes, and in chimeric mice with humanized livers. To analyze the involvement of glycosaminoglycan, HBs-S attachment to cells in the presence of heparin was evaluated by enzyme-linked immunosorbent assay (ELISA), and the enhancement of viral attachment was evaluated by measurement of viral DNA. Additionally, the interaction between HBs-S and viral particles was analyzed by immunoprecipitation.ResultsAttachment of the HBV DNA to cells inoculated with the combination of virus and HBs-S was significantly higher than that to cells inoculated with HBV only. Pretreatment of the cells with HBs-S also increased viral DNA levels significantly compared to that in untreated cells. In contrast, HBs-L did not enhance the viral attachment. Enhancement of viral attachment was associated with the attachment of HBs-S to the cells via heparan sulfate. HBs-S also interacted with the viral particle. Furthermore, in chimeric mice with humanized livers, HBs-S enhanced HBV infection.ConclusionsWe demonstrated that HBs-S enhances viral attachment in vitro and viral infection in vivo. HBs-S interacted with heparan sulfate on the cellular surface, and this interaction contributed to the enhancement of viral attachment. These data indicate that HBs-S enhances the viral infection, and may contribute to the high transmissibility of HBV.