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Developing new adjuvants that can effectively induce humoral and cellular immune responses while broadening the immune response is of great value. In this study, we aimed to develop single-stranded RNA adjuvants expressing (1) granulocyte monocyte colony-stimulating factor or (2) interleukin 18 based on the encephalomyocarditis virus internal ribosome entry site; we also tested their efficacy in combination with ovalbumin or inactivated influenza vaccines. Notably, cytokine-expressing RNA adjuvants increased the expression of antigen-presenting cell activation markers in mice. Specifically, when combined with ovalbumin, RNA adjuvants expressing granulocyte monocyte colony-stimulating factor increased CD4+ T-cell responses, while those expressing interleukin 18 increased CD8+ T-cell responses. Cytokine-expressing RNA adjuvants further increased the frequency of polyclonal T cells with the influenza vaccine and reduced the clinical illness scores and weight loss of mice after viral challenge. Collectively, our results suggest that cytokine-expressing RNA adjuvants can be applied to protein-based or inactivated vaccines to increase their efficacy. [ABSTRACT FROM AUTHOR]

The E6 and E7 proteins of specific subtypes of human papillomavirus (HPV), including HPV 16 and 18, are highly associated with cervical cancer as they modulate cell cycle regulation. The aim of this study was to investigate the potential antitumor effects of a messenger RNA‐HPV therapeutic vaccine (mHTV) containing nononcogenic E6 and E7 proteins. To achieve this, C57BL/6j mice were injected with the vaccine via both intramuscular and subcutaneous routes, and the resulting effects were evaluated. mHTV immunization markedly induced robust T cell‐mediated immune responses and significantly suppressed tumor growth in both subcutaneous and orthotopic tumor‐implanted mouse model, with a significant infiltration of immune cells into tumor tissues. Tumor retransplantation at day 62 postprimary vaccination completely halted progression in all mHTV‐treated mice. Furthermore, tumor expansion was significantly reduced upon TC‐1 transplantation 160 days after the last immunization. Immunization of rhesus monkeys with mHTV elicited promising immune responses. The immunogenicity of mHTV in nonhuman primates provides strong evidence for clinical application against HPV‐related cancers in humans. All data suggest that mHTV can be used as both a therapeutic and prophylactic vaccine. [ABSTRACT FROM AUTHOR]

Zika virus (ZIKV) infection is primarily transmitted by mosquitoes and often asymptomatic in most individuals. Infection during pregnancy can lead to severe birth defects such as congenital microcephaly, and currently, there is no approved vaccine for ZIKV. Several studies are investigating the development of ZIKV vaccine using DNA and RNA as well as recombinant protein technologies; however, the outcomes thus far have not been consistently noteworthy. In this study, we designed an mRNA vaccine for ZIKV and evaluated its immunogenicity using a mouse model. Our vaccine, termed 3xEIII, encodes a triple repeat of domain III from the ZIKV E protein. We effectively encapsulated the mRNA within lipid nanoparticles (LNPs), administered 3xEIII to mice via two intramuscular injections, and assessed the induced humoral and cellular immune responses. Specifically, the vaccine elicited neutralizing antibodies that effectively eliminated ZIKV from the organs of challenged mice. Notably, 3xEIII conferred both protective effects and long-term immunity. In subsequent challenges conducted 40 weeks after boosting, immunized mice experienced temporary weight loss but showed significantly reduced viral titers in target organs by the 9th day post-infection. Conclusively from these findings, 3xEIII stands out as a promising noteworthy mRNA vaccine candidate for Zika virus. • The vaccine targets domain III of the ZIKV E protein essential for virus entry. • The ZIKV mRNA vaccine effectively induces neutralizing antibody responses in mice. • The vaccine activates T and B cell responses to promote cellular and humoral immunity. • Long-term immunity is evident with lower viral titers in organs after the boost. [ABSTRACT FROM AUTHOR]