ABSTRACT
Mucosal vaccinations for respiratory pathogens provide superior protection as they stimulate localized cellular and humoral immunity at the site of infection. Currently, the major limitation of the intranasal vaccination is using effective adjuvants capable of withstanding the harsh environment imposed by the mucosa. Herein, we describe the efficacy of using a novel biopolymer, N-dihydrogalactochitosan (GC), as a nasal mucosal vaccine adjuvant against respiratory infections. Specifically, using COVID as an example, we mixed GC with recombinant SARS-CoV-2 trimeric spike (S) and nucleocapsid (NC) proteins to intranasally vaccinate K18-hACE2 transgenic mice, in comparison with Addavax (AV), an MF-59 equivalent. In contrast to AV, intranasal application of GC induces a robust, systemic antigen-specific antibody response and increases the number of T cells in the cervical lymph nodes. Moreover, GC+S+NC vaccinated animals were largely resistant to lethal SARS-CoV-2 challenge and experienced drastically reduced morbidity and mortality, with the animal weights and behavior returning to normal 22 days post infection. In contrast, animals intranasally vaccinated by AV+S+NC experienced severe weight loss, mortality, and respiratory distress, with none surviving beyond 6 days post infection. Our findings demonstrate that GC can serve as a potent mucosal vaccine adjuvant against SARS-CoV-2 and potentially other respiratory viruses.