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Introduction: Japanese encephalitis virus (JEV) and Zika virus (ZIKV) pose a severe threat to human health. Our previous research results, as well as those of other research groups, indicated that antibodies (Abs) induced by JEV infection or JEV vaccine vaccination could enhance ZIKV infection in vitro and exacerbate the mortality of ZIKV-infected mice, vice versa, which is known as antibody-dependent enhancement (ADE). Although studies on other flaviviruses revealed that altering the amino acid residues located in the fusion loop (FL) of envelope (E) protein can reduce the level of flavivirus-cross-reactive Abs, thereby abating the ADE of heterologous flavivirus infection, it is unclear whether this strategy is equally applicable to JEV. Methods: In this study, we constructed recombinant adenoviruses and nucleotide-modified mRNA-lipid nanoparticle (LNP) encoding JEV wild-type E protein or E protein mutant (designated as Ad5-JEV-EWT and Ad5-JEV-Emut; JEV-EWT mRNA-LNP, and JEV-Emut mRNA-LNP). We evaluated the immunogenicity of these vaccine candidates in mice and the capacity of vaccine-immune mouse sera to neutralize JEV infection or mediate ADE of ZIKV infection in vitro and in vivo. Results: Ad5-JEV-Emut or JEV-Emut mRNA-LNP immunization induced ZIKV-cross-reactive Ab response which is dramatically lower than that induced by Ad5-JEV-EWT and JEV-EWT mRNA-LNP, respectively. The levels of JEV-neutralizing Abs induced by Ad5-JEV-Emut or JEV-Emut mRNA-LNP are comparable to that induced by Ad5-JEV-EWT and JEV-EWT mRNA-LNP, respectively. The ability of Abs induced by Ad5-JEV-Emut to enhance ZIKV infection in vitro is attenuated as compared with that induced by Ad5-JEV-EWT. Moreover, JEV-Emut mRNA-LNP immunization elicited potent T cell response similar to JEV-EWT mRNA-LNP in mice. Mice immunized with each mRNA-LNP exhibited lower level of serum viral load than the mock-immunized mice post JEV challenge. Mice receiving JEV-EWT mRNA-LNP-immune mouse sera exhibited ADE post ZIKV challenge whereas passively transferred JEV-Emut mRNA-LNP-immune mouse sera did not lead to obvious ADE of ZIKV infection in recipient mice. Most importantly, maternally acquired Abs did not enhance the mortality of 1-day-old neonates born to JEV-Emut mRNA-LNP-immunized mice post ZIKV challenge. Discussion: These results suggest that optimizing the FL sequence of JEV could significantly reduce the level of JEV/ZIKV-cross-reactive Abs and abrogate the ADE of ZIKV infection, providing a promising strategy to develop effective and safety JEV vaccine. [ABSTRACT FROM AUTHOR]

The conventional anodic oxygen evolution reaction (OER) can be ideally replaced by the urea oxidation reaction (UOR) to achieve efficient hydrogen generation due to the superior thermodynamics. However, the UOR involves a slow 6-electron transfer dynamic, necessitating the utilization of high-performance catalysts to enhance catalytic efficiency. In this work, a bifunctional transition metal-based catalysts, namely, MoO 2 –NiO/NF heterostructure, is effectively synthesized using two-step hydrothermal methods and calcination. Benefiting from the heterogeneous interface, the nanoflower-like structure as well as the electron density redistribution, the MoO 2 –NiO/NF catalyst demonstrates remarkable durability and performance, with an overpotential of 139 mV to achieve 10 mA cm−2 for UOR. In addition, the bifunctional catalyst is used in a two-electrode electrolyzer, where a current density of 10 mA cm−2 is attained at a potential of 1.317 V, which is 261 mV smaller than that of the conventional water splitting system. Based on the density functional theory (DFT) calculations, the MoO 2 –NiO/NF heterostructure exhibits a higher density cloud in the vicinity of the Fermi level, revealing that it has faster electron transfer and higher electrical conductivity. Besides, the Mo sites and Ni sites are favorable for adsorption of CO(NH 2) 2 and H 2 O, respectively, which might optimize the reaction intermediates adsorption/desorption for UOR/HER, ultimately leading to the high electrocatalytic performance of MoO 2 –NiO/NF. This research opens a new window for the development of advanced heterojunction electrocatalysts assisted by urea electrocatalysis for cost-effective hydrogen production. Using hydrothermal and calcination techniques, high-performance MoO 2 –NiO/NF nanoflower-like heterostructures for bifunctional urea-assisted water splitting are created. In the HER||UOR two-electrode system, the MoO 2 –NiO/NF heterostructure only required 1.32 V at 10 mA cm−2, which is about 261 mV smaller than that of the traditional water electrolysis. [Display omitted] • Heterostructured nanoflower-like MoO 2 –NiO/NF electrocatalyst is synthesized. • MoO 2 –NiO/NF shows superb activity and stability in urea-assisted water splitting. • The bifunctional catalyst exhibits enhanced electrocatalytic HER/UOR performance. • Heterointerface has fast electron transfer and high electrical conductivity. • Mo and Ni sites are selective for the adsorption of urea and H 2 O molecules. [ABSTRACT FROM AUTHOR]