A single immunization with intranasal Newcastle disease virus (NDV)-based XBB.1.5 variant vaccine reduces disease and transmission in animals against matched-variant challenge

The rapid development of coronavirus disease 2019 (COVID-19) vaccines has helped mitigate the initial impact of the pandemic. However, in order to reduce transmission rates and protect more vulnerable and immunocompromised individuals unable to mount an effective immune response, development of a next-generation of mucosal vaccines is necessary. Here, we developed an intranasal Newcastle disease virus (NDV)-based vaccine expressing the spike of the XBB.1.5 variant stabilized in its pre-fusion conformation (NDV-HXP-S). We demonstrated that one or two intranasal immunizations with live NDV-HXP-S expressing the XBB.1.5 spike induces systemic and mucosal antibody responses in mice and protects them from a challenge with the XBB.1.5 variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Furthermore, one or two intranasal vaccinations with NDV-HXP-S XBB.1.5 protected hamsters from variant matched infection and reduced virus emission, thereby providing complete protection to naïve animals in a direct contact transmission study. The data shown in this study supports the notion that intranasal vaccination with variant-adapted NDV-HXP-S induces protective mucosal immunity and reduces transmission rates, highlighting the robust protective efficacy of a single mucosal vaccination in mice and hamsters.