Self-assembled multiepitope nanovaccine based on NoV P particles induces effective and lasting protection against H3N2 influenza virus.

Current seasonal influenza vaccines confer only limited coverage of virus strains due to the frequent genetic and antigenic variability of influenza virus (IV). Epitope vaccines that accurately target conserved domains provide a promising approach to increase the breadth of protection; however, poor immunogenicity greatly hinders their application. The protruding (P) domain of the norovirus (NoV), which can self-assemble into a 24-mer particle called the NoV P particle, offers an ideal antigen presentation platform. In this study, a multiepitope nanovaccine displaying influenza epitopes (HMN-PP) was constructed based on the NoV P particle nanoplatform. Large amounts of HMN-PP were easily expressed in Escherichia coli in soluble form. Animal experiments showed that the adjuvanted HMN-PP nanovaccine induced epitope-specific antibodies and haemagglutinin (HA)-specific neutralizing antibodies, and the antibodies could persist for at least three months after the last immunization. Furthermore, HMN-PP induced matrix protein 2 extracellular domain (M2e)-specific antibody-dependent cell-mediated cytotoxicity, CD4+ and CD8+ T-cell responses, and a nucleoprotein (NP)-specific cytotoxic T lymphocyte (CTL) response. These results indicated that the combination of a multiepitope vaccine and self-assembled NoV P particles may be an ideal and effective vaccine strategy for highly variable viruses such as IV and SARS-CoV-2. Electronic Supplementary Material: Supplementary material is available in the online version of this article at 10.1007/s12274-023-5395-6.

Updated information regarding acute severe hepatitis of unknown origin in children: Viewpoints of and insights from pediatricians.

Recently, the morbidity of acute severe hepatitis of unknown origin in children (SHIC) has tended to decrease, but this condition should not be ignored because of its uncertain but severe nature. The current study briefly summarizes updated information regarding the epidemiological, clinical, and etiological aspects of SHIC based on the newest information available. Opinions from pediatricians are also presented. In light of the status quo of SHIC and COVID-19 globally, several suggestions are proposed to improve future studies, which could help to further explore the underlying mechanisms of SHIC in the context of COVID-19.

Investigation of a Mask Fitness Test Based on Self-Efficacy and Diversified Training in the Assessment System for Nosocomial Infection Training.

Objective: To explore a mask fitness test based on self-efficacy and diversified training in the assessment system for nosocomial infection training. Methods: From March 15 to April 5, 2022, 442 staff members (272 male and 170 female) of the Third People's Hospital of Shenzhen who planned to enter the quarantine ward for secondary protection skill training assessment were selected. They comprised 56 doctors, 31 medical technicians, 72 nurses, and 283 property logistics staff. During the mask fitness test, a diversified training model based on self-efficacy was adopted to observe the passing status, the identification and selection of mask models, the method of mask-wearing, the fit between the mask and the face, and the changes in self-efficacy. Results: In the assessment system for nosocomial infection training, the passing rate of the mask fitness test was correlated with the identification and selection of mask models, the method of wearing masks, the fit between the mask and the face, and the diversified training, and the differences were statistically significant (P < 0.05). The difference in the self-efficacy in the test takers between those before and after the mask fitness test was statistically significant (P < 0.05). Conclusion: In the assessment system for nosocomial infection training, the mask fitness test based on self-efficacy and diversified training might improve the passing rate, the rate of correct mask model identification and selection, the rate of correct mask-wearing, and the degree of facial fit, thus to enhance the awareness of protection and improve self-efficacy.

Engineered ACE2-Fc counters murine lethal SARS-CoV-2 infection through direct neutralization and Fc-effector activities.

Soluble angiotensin-converting enzyme 2 (ACE2) constitutes an attractive antiviral capable of targeting a wide range of coronaviruses using ACE2 as their receptor. Using structure-guided approaches, we developed a series of bivalent ACE2-Fcs harboring functionally and structurally validated mutations that enhance severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor binding domain recognition by up to ~12-fold and remove angiotensin enzymatic activity. The lead variant M81 potently cross-neutralized SARS-CoV-2 variants of concern (VOCs), including Omicron, at subnanomolar half-maximal inhibitory concentration and was capable of robust Fc-effector functions, including antibody-dependent cellular cytotoxicity, phagocytosis, and complement deposition. When tested in a stringent K18-hACE2 mouse model, Fc-enhanced ACE2-Fc delayed death by 3 to 5 days or effectively resolved lethal SARS-CoV-2 infection in both prophylactic and therapeutic settings via the combined effects of neutralization and Fc-effector functions. These data add to the demonstrated utility of soluble ACE2 as a valuable SARS-CoV-2 antiviral and indicate that Fc-effector functions may constitute an important component of ACE2-Fc therapeutic activity.