Protective immunity in hamsters from an oral Nipah vaccine correlates with pseudovirus neutralising antibody titre.

Nipah virus (NiV) is a deadly zoonotic pathogen with a high mortality rate and no approved vaccines, creating an urgent need for new solutions. We developed a novel, thermostable, orally administered NiV vaccine using a human serotype 5 adenovirus (AdHu5) vector to express NiV glycoproteins G and F. This vaccine, delivered via an enteric-coated capsule using the OraPro platform, eliminates the cold chain and allows for self-administration. In a Syrian hamster model, a prime-and-pull strategy—an intramuscular prime followed by an oral booster—provided 100% protection against a lethal NiV challenge, significantly outperforming intramuscular administration alone, which offered only 66% protection. The oral booster also led to higher serum neutralizing antibody titres while reducing anti-vector immunity, potentially enabling repeated use of the same vector. Histopathological analysis showed superior protection in orally boosted animals, with minimal lung lesions. This study highlights the potential of oral vaccines for addressing emerging infectious diseases.