An LSRFortessa flow cytometer (BD Biosciences) and FlowJo software (TreeStar) were used for data collection and analysis, respectively. development. Our constructed zEDIII-rHF nanovaccine, with superior Letaxaban (TAK-442) protective performance and avoidance of ADE, provides an effective and safe vaccine candidate against ZIKV. Keywords: zika computer virus, nanovaccine, ferritin, ZIKV envelop protein domain name III, antibody-dependent enhancement Introduction Zika computer virus (ZIKV) is an arboviral computer virus belonging to the family. ZIKV is usually defined as a serious public health problem by the World Health Business (WHO) because it is usually widespread in many countries, with cases of severe birth defects being documented (1, 2). ZIKV also causes severe neurological diseases, such as microcephaly, GuillainCBarr syndrome, meningoencephalitis, and myelitis (3, 4). Although control and preventive measures have been taken, to date, there are no vaccines or specific antiviral drugs against ZIKV. Several platforms have been tried to develop ZIKV vaccines. For example, live attenuated ZIKV vaccine candidates have been generated by deleting 10 nucleotides in the 3-untranslated region (UTR) of the ZIKV genome or using the codon pair deoptimization strategy (5). An inactivated full-virus ZIKV vaccine was also developed and induced protection against ZIKV contamination (6). However, attenuated live vaccines have hidden dangers, such as infectious residues, and inactivated ZIKV causes immune-related side effects (7). As the envelope (E) protein and NS1 protein are major targets of host antibody responses, they were also considered candidates for ZIKV vaccines. Li et?al. developed an attenuated recombinant vesicular stomatitis computer virus (rVSV) expressing a ZIKV prM-E-NS1 polyprotein (8). This rVSV could induce ZIKV-specific antibodies and a T cell immune response and protect mice against ZIKV contamination. DNA or RNA vaccination based on the ZIKV prM-E gene sequence could also induce strong neutralizing antibodies (NAbs) and a T cell immune response Letaxaban (TAK-442) and effectively improve the survival rate in mice (9). However, for these candidates, due to the complex preparation processes and stringent Letaxaban (TAK-442) storage conditions, there are obstacles limiting large-scale production (10). More importantly, these E protein-based vaccines may cause antibody-dependent enhancement (ADE) and have the potential risk of enhancing other flavivirus infections (11, 12). The nonneutralizing cross-reactive antibodies generated during a previous flavivirus contamination can increase the pathogenesis of a related computer virus, which is called ADE (13). ADE is particularly common between ZIKV and dengue computer virus (DENV) (14, 15). ADE is usually a challenge in vaccine development for flaviviruses, including ZIKV. Approaches to make sure high protective efficacy while avoiding ADE are an important focus in the development of ZIKV vaccines (15). Recently, it was found that ZIKV E protein domain name III (zEDIII) can evoke ZIKV-specific antibody and NAb responses without ADE activity for DENV contamination (16, 17). Thus, vaccines based on the zEDIII antigen are potential protein subunit vaccine candidates for ZIKV contamination. However, the zEDIII subunit has low immunogenicity (18), which limits it to be developed as protective vaccine. Self-assembling nanotechnology provides an opportunity for the development of vaccines with superior performance (19C21). Nanoparticles can promote antigen delivery and immune induction (22C25). By presenting the influenza A computer virus (IAV) trimeric HA or M2e on self-assembling ferritin, nanoparticle vaccines have been developed to confer influenza protection (26). Other nanoparticle vaccines have been tried to prevent Dengue computer virus and Hepatitis B computer virus (27, 28). Recently, nanoparticle-based vaccine Rabbit Polyclonal to CKI-epsilon against SARS-CoV-2 was also reported (29). These nanoparticle vaccines cause more efficacious immune response and protection, which provides a promising strategy for vaccine construction. In this study, we developed a self-assembling nanovaccine to protect against ZIKV contamination. By displaying.