An Intein-Spliced Nipah G Protein Ferritin Nanoparticle Vaccine Provides Complete Protection against Lethal Nipah Virus Challenge

Nipah virus (NiV) is a serious hazard to human health since it can cause severe respiratory infections and viral encephalitis with a high fatality rate. Given the lack of a licensed NiV vaccine, there is an urgent need to develop one to protect public health. Previously, we developed NiV G protein nanoparticle vaccines by loading G protein onto ferritin nanoparticles (FeNP) via SpyCatcher/SpyTag technology, resulting in nanoparticles with three layers (FeNP-SC/ST-G_head), including the inner core of ferritin (20 kDa), the intermediate layer of covalently linked SpyCatcher/SpyTag (11.2 kDa) and the outer layer of G protein. The intermediate layer is unnecessary in terms of immunization and occupies immune resources in the body. In this study, we used a split-intein to conjugate NiV G_head onto FeNP, yielding FeNP-G_head with two layers. In BALB/c mice, FeNP-G_head could avoid immune response against SpyCatcher, elicit high levels of specific humoral immune responses for up to 217 days and long-lasting Th1-biased cellular immune responses. Furthermore, FeNP-G_head showed potent protection efficacy in the hamster model, with immunization of 1 μg providing 100% protection against challenge with 1000 LD₅₀ of NiV, and even as low as 0.2 μg being partially protective (83% survival). Since FeNP-G_head has a lower protein content than FeNP-SC/ST-G_head, it will occupy fewer immune resources in vivo, thereby reduce the potential for adverse immune side effect.