A single-dose chimeric Newcastle disease virus (NDV)/chikungunya virus (CHIKV) is an effective CHIKV vaccine...

With the broad spread of the chikungunya virus (CHIKV), there is an increasing demand for more effective and protective vaccines. In this study, we first developed a Newcastle disease virus (NDV) vector vaccine candidate expressing the complete envelope (E3-E1) protein of CHIKV. The immunoelectron microscopy confirmed the presence of E2 protein in the rNDV-CHIKV virion, and the virological results showed that the expression of E1 and E2 protein was stable after 10 serial passages in embryonated chicken eggs. Moreover, we assessed its safety and immunogenicity following intramuscular (i.m.) or subcutaneous (s.c.) administration in C57BL/6 mice. The immunogenicity analyses demonstrated that a single-dose immunization elicits high titers of CHIKV E2-specific IgG antibodies, potent neutralizing activity, and T-cell immune responses. Importantly, both routes of immunization conferred complete protection against wild-type CHIKV challenge in C57BL/6 mice. These findings present a promising novel vector-based vaccine candidate with significant potential for effective CHIKV prevention.IMPORTANCEChikungunya virus (CHIKV) imposes a substantial global health burden, characterized by arthralgia that can persist for years, neurological complications, and potentially fatal outcomes in vulnerable populations. Currently, two vaccines against CHIKV have been approved: a live-attenuated vaccine (Ixchiq) and a virus-like particle (VLP) vaccine (Vimkunya). However, Ixchiq has been withdrawn from clinical use due to significant side effects, highlighting the urgent need for the development of novel vaccine strategies. Our research has successfully developed a novel vaccine candidate that utilizes Newcastle disease virus as a vector to express CHIKV antigens. This innovative strategy offers multiple advantages: cost-effectiveness, genetic stability of the inserted gene, and robust immunogenicity with effective immune protection. This approach offers a contribution in addressing the emerging threat posed by CHIKV.