Comparative immunogenicity of monomeric and tetrameric Nipah virus G glycoprotein-based vaccine candidates demonstrate robust antibody responses in both forms.

Nipah virus (NiV) is a highly pathogenic zoonotic virus with no licensed vaccine. The G surface glycoprotein of NiV plays a critical role in host cell attachment and is a prime vaccine target. In this study, we designed and expressed two soluble recombinant variants of the G glycoprotein-monomeric and tetrameric forms-using a mammalian expression system to preserve the native-like structure. Both proteins were biochemically stable as measured up to one month at temperatures ranging from 2 to 8 °C and - 20 °C. While the monomer had a higher yield in transient expression, the tetramer more closely mimicked the native multimeric architecture and showed better biophysical stability. BALB/c mice immunized with either variant, along with AddaVax adjuvant, generated robust, long-lasting antibody and neutralizing responses persisting up to six months. Collectively, our findings demonstrate the robust immunogenicity of both soluble monomeric and tetrameric G immunogens, with the monomeric form offering high scalability, underscoring their suitability as subunit vaccine candidates against Nipah virus.