Influenza virus is a prominent cause of respiratory illness in humans. Current influenza vaccines offer strain-specific immunity, while provide limited protection against drifted strains. Broad-spectrum influenza vaccines can induce broad and long-term immunity, and thus is regarded as a future direction for the development of next-generation influenza vaccines. In this study, we have conceptualized a novel mRNA-based multi-antigen influenza vaccine consisting of three conserved antigens of influenza A virus, including the ectodomain of the M2 ion channel (M2e), the long alpha helix of haemagglutinin stalk region (LAH), and nucleoprotein (NP). The vaccine design aims to enhance its potency and promote the development of a future broad-spectrum influenza vaccine. Our mRNA-based vaccine demonstrated potent humoral and cellular responses throughout the time points of the murine model, inducing viral neutralizing antibodies, antibody-dependent cell cytotoxicity effect mediating antibodies and cross-reactive CD8⁺ T cell immune responses. The vaccine conferred broad protection against H1N1, H3N2, and H9N2 viruses. Moreover, the single-cell transcriptional profiling of T cells in the spleens of vaccinated mice revealed that the mRNA-based vaccine significantly promoted CD8⁺ T cells and memory T cells by prime-boost immunization. Our results suggest that the mRNA-based influenza vaccine encoding conserved proteins is a promising approach for eliciting broadly protective humoral and cellular immunity against various influenza viruses.

Herpangina (HA) and hand, foot, and mouth disease (HFMD) are common infectious diseases caused by human enteroviruses and frequently occurr in young children. Previous published studies have mainly focused on HFMD, while the HA epidemiological and etiological characteristics in mainland China have not been described. From June, 2013 to March, 2014, HA and HFMD patients were monitored in participants from clinical trial of EV-A71 vaccine conducted during 2012–2013. A total of 95 HA patients and 161 HFMD patients were defined. Enteroviruses of HA samples were differentiated into 17 serotypes (EV-A71, CV-A16, CV-A24, E6, CV-B5, CV-A22, CV-A6, CV-A10, CV-B3, E9, CV-A9, CV-B4, CV-B2, E1, E7, E21 and CV-A20), the most common serotypes were EV-A71(10/95,10.5%), CV-A16(4/95,4.2%) and CV-A24(4/95,4.2%); while enteroviruses detected from HFMD samples were classfied into 21 serotypes ( EV-A71, CV-A16, CV-A10, CV-A6, E6, CV-B3, CV-B5, CV-A9, E9, CV-B2, CV-B4, E3, E11, E15, E16, CV-A1, EV-A69, E5, CA22, CA24 and EV99), the most common serotypes were EV-A71(28/161,17.4%), CV-A16(7/161,4.4%) and CV-A10(5/161,3.1%). The first HA epidemic peak occurred in summer and a second smaller peak occurred in January. In HA patients, the body temperature (P < 0.0001) and the incidence of fever (P < 0.05) were significant higher than those in HFMD patients. Between HA and HFMD patients infected with EV-A71, no significant differences were found in age, sex, circulating season, and the viral genome diversity. In summary, we firstly reported the epidemiological and etiological characteristics of HA in mainland China. Developing a multivalent vaccine will be helpful for the control of the HA/HFMD epidemic.

Mpox (monkeypox) infection cases increased recently in non-Mpox outbreak areas, potentially causing an international threat. The desire to defend against a potential outbreak has led to renewed efforts to develop Mpox vaccines. In this report, mice were immunized with various doses of modified vaccinia virus Ankara (MVA) to evaluate the cross-reactive immune response of MVA immunization against protective antigens of the current monkeypox virus. We demonstrated that MVA induced specific antibodies against protective antigens (A29, A35, B6, M1, H3, and I1), mediating the neutralization abilities against the MVA and the monkeypox virus (MPXV). Moreover, recombinant protective antigens of the MPXV elicited cross-binding and cross-neutralizing activities for MVA. Hence, the MVA induced cross-reactive immune responses, which may guide future efforts to develop vaccines against the recent MPXV. Notably, compared to the other protective antigens, the predominant A29 and M1 antigens mediated higher cross-neutralizing immune responses against the MVA, which could serve as antigen targets for novel orthologous orthopoxvirus vaccine.

Since some cases of human infections with H5N8 avian influenza virus have been reported and caused great concern in recent years, it is important to develop an effective vaccine for human use to prevent a potential H5N8 pandemic. In the present study, a vaccine candidate virus based on newly human-infected A/Astrakhan/3212/2020 H5N8 virus was constructed by reverse genetics (RG) technology. The immunogenicity of H5N8 whole virion inactivated vaccine was evaluated by various doses of vaccine antigen formulated with squalene-based adjuvant (AddaVax), aluminum hydroxide (Al(OH)₃) or without adjuvant in mice. The results showed AddaVax-adjuvanted H5N8 inactivated vaccine could stimulate the mice to produce a stronger protective immune response with higher titers of IgG antibodies, hemagglutination inhibition (HI), neuraminidase inhibition (NI) and microneutralization (MN) antibodies than vaccine formulations with Al(OH)₃ adjuvant or without adjuvant, and achieve a dose-sparing effect. Moreover, the AddaVax-adjuvanted formulation also exhibited potent cross-reactive response in HI antibodies against different clades of H5 viruses. A significant correlation and a curve fitting among HI, NI and MN were found by the correlation analysis to predict the protective effect of the vaccine. With these findings, our study demonstrates that AddaVax adjuvant can enhance the immunogenicity of H5N8 inactivated vaccine remarkably, and proposes an effective strategy for dealing with a potential H5N8 virus pandemic.

• Analyzed the outbreak situation and viral characteristics of the newly H5N1 highly pathogenic avian influenza (HPAI) virus. • The current approval and research and development of the H5N1 HPAI vaccines were summarized. • Proposed vaccine development approaches against newly H5N1 virus, e.g. adjuvanted vaccine, mRNA vaccine, multivalent vaccine. • Discussed other prevention and control strategies, e.g. poultry vaccination, global surveillance and comprehensive testing.