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Although the current hepatitis B (HB) vaccine comprising yeast-derived small hepatitis B surface antigen (HBsAg) is potent and safe and used worldwide, specific concerns should not be ignored, such as the attenuated prophylaxis against hepatitis B virus (HBV) infection with specific amino acid polymorphisms, called vaccine-escape mutations (VEMs). We investigated a novel HB vaccine consisting of large-HBsAg that covers the shortcomings of the current HB vaccine in a nonhuman primate model. The yeast-derived large-HBsAg was mixed with the adjuvant and used to immunize rhesus macaques, and the induction of antibodies to HBsAg was compared with that of the current HB vaccine. The current HB vaccine predominantly induced antibodies to small-HBsAg, whereas immunization with the large-HBsAg vaccine mainly induced antibodies to the preS1 region. Although the antibodies induced by the current HB vaccine could not prevent infection of HBV with VEMs, the large-HBsAg vaccine-induced antibodies neutralized infection of HBV with VEMs at levels similar to those of the wild type. The HBV genotypes that exhibited attenuated neutralization by induced antibodies differed between these vaccines. In conclusion, the novel HB vaccine consisting of large-HBsAg was revealed to be useful to compensate for shortcomings of the current HB vaccine. The combined use of these HB vaccines may be able to induce antibodies that can neutralize HBV strains with VEMs or multiple HBV genotypes.

More than 40 years after the discovery of human sapovirus (HuSaV), we have established a HuSaV culture system in which HuTu80 cells derived from the human duodenum adenocarcinoma cell line are cultured together with the addition of bile acid as a supplement. In addition to being a common cell line, this system using HuTu80 cells is a versatile method because classical culture media are available, and it is easy to scale-up for culture. However, the number of culture days required to obtain sufficient viral titer, the confirmation of viral gene conservation for sample selection, and the method for passaging of HuTu80-cells were crucial. So far, 15 genotypes have been successfully propagated and stocked, and stable supply as research resources has been achieved. Due to the above efforts, we can now proceed with the production and analysis of antisera using purified antigens and the evaluation of inactivation conditions. This manuscript introduces the background for selection of the cell line and bile acids, and the topics that have been discussed since the publication, as well as future issues that were raised such as the expression of cytopathicity and elucidation of low UV-C sensitivity of fecal-derived HuSaV.

Noroviruses are the most common viral cause of acute gastroenteritis after the introduction of rotavirus vaccines. Norovirus infection can cause severe symptoms in vulnerable populations including young children and the elderly. Thus, it is still a leading cause of death from diarrhea in children in developing countries. Recent advancement of genomics platforms facilitated understanding of the epidemiology of norovirus, while the whole picture of norovirus diversity is still undetermined. Currently, there are no approved vaccines for norovirus, but state-of-the-art norovirus cultivation systems could elucidate the antigenic diversity of this fast-evolving virus. In this review, we will summarize the historical and latest findings of norovirus epidemiology, diversity, and evolution.

It has been passed four years since the pandemic caused by the severe acute respiratory syndrome-2 (SARS-CoV-2) that began in 2019. Since June 2020, we have been working on a project to develop a therapeutic drug using receptor decoys, even though we cannot predict how long the pandemic will last or how long our daily lives will be restricted. This receptor decoy utilizes Angiotensin-converting enzyme 2 (ACE2), which is the receptor for SARS-CoV-2, and involves introducing mutations that enhance its binding ability with the spike protein of SARS-CoV-2. This high-affinity ACE2, acting as a decoy protein, is a strategy to inhibit viral infection and to expect therapeutic effects by replacing the endogeneous ACE2 that SARS-CoV-2 binds to with ACE2 decoy. This paper introduces the development of ACE2 decoys that have progressed through collaborative research with many researchers outside the field of virology.