A VLPs based vaccine protects against Zika virus infection and prevents cerebral and testicular damage.

Still, Zika virus (ZIKV) infection poses a substantial public health risk, especially for pregnant women and their fetuses, as it can result in congenital abnormalities and fetal mortality during pregnancy. Despite significant advances in understanding and combating ZIKV, considerable challenges remain in the fight against this flavivirus. A crucial component of this effort is the development of vaccines, none of which have yet been licensed for human use. Here, we present a comprehensive study of a novel ZIKV vaccine candidate based on virus-like particles (VLPs), designed to provide broad immunological protection against viral infection combined with safety, without the need for additional adjuvants. A self-adjuvanted VLPs-based vaccine displaying the envelope protein domain III (EDIII) of ZIKV was built. The EDIII protein was expressed in E. coli and chemically conjugated to QβVLPs. Immunization of C57BL/6 mice with two doses of the EDIII-QβVLPs vaccine elicited strong EDIII-specific Th1-based immune response. Notably, the vaccine induced neutralizing antibodies and conferred protection in type I IFN receptor-deficient (G129) mice against ZIKV challenge. Furthermore, vaccinated male mice were protected from ZIKV-induced cerebral and testicular damage, critical concerns for ZIKV pathogenesis. These findings suggest that the EDIII-QβVLP vaccine is a promising candidate for preventing ZIKV infection, with potential applications in combatting this and other emerging flaviviruses.