Efficacy of mucosal polyanhydride nanovaccine against respiratory syncytial virus infection in the neonatal calf

Abstract

Human respiratory syncytial virus (HRSV) is a leading cause of severe acute lower respiratory tract infection in infants and children worldwide. Bovine RSV (BRSV) is closely related to HRSV and a significant cause of morbidity in young cattle. BRSV infection in calves displays many similarities to RSV infection in humans, including similar age dependency and disease pathogenesis. Polyanhydride nanoparticle-based vaccines (i.e., nanovaccines) have shown promise as adjuvants and vaccine delivery vehicles due to their ability to promote enhanced immunogenicity through the route of administration, provide sustained antigen exposure, and induce both antibody- and cell-mediated immunity. Here, we developed a novel, mucosal nanovaccine that encapsulates the post-fusion F and G glycoproteins from BRSV into polyanhydride nanoparticles and determined the efficacy of the vaccine against RSV infection using a neonatal calf model. Calves receiving the BRSV-F/G nanovaccine exhibited reduced pathology in the lungs, reduced viral burden, and decreased virus shedding compared to unvaccinated control calves, which correlated with BRSV-specific immune responses in the respiratory tract and peripheral blood. Our results indicate that the BRSV-F/G nanovaccine is highly immunogenic and, with optimization, has the potential to significantly reduce the disease burden associated with RSV infection in both humans and animals.

Supplementing a Saccharomyces cerevisiae fermentation product modulates innate immune function and ameliorates bovine respiratory syncytial virus infection in neonatal calves

“…For logistical purposes, the viral challenges were staggered by 24 h, with 7 to 8 calves/d receiving the virus, balanced by treatment. Animals were challenged via aerosol inoculation with ~10 4 Tissue Culture Infectious Dose (TCID) 50 BRSV strain 375 as we have previously described ( McGill et al, 2016 , 2018 , 2019a ). Briefly, the viral inoculum was suspended in 5 mL and delivered via forced-air nebulizer to a mask covering the nose and mouth of the calf.…”

Synthesis and Characterization of Rapidly Degrading Polyanhydrides as Vaccine Adjuvants

“…Controlling copolymer composition has been shown to enhance cellular uptake 32,33 , ultimately resulting in chemistrydependent immunomodulatory capabilities 34,35 . These materials represent an efficacious vaccine adjuvant platform, as evidenced by sustained antibody responses to numerous antigens 10,11,15,16,36 , enhanced germinal center formation 37 , increased cytotoxic T cell responses 38 , and protection against multiple bacterial and viral infections 10,13,17 .…”

Adenovector 26 encoded prefusion conformation stabilized RSV-F protein induces long-lasting Th1-biased immunity in neonatal mice

“…ΔF/TriAdj, a truncated adjuvanted fusion protein, was shown to be immunogenic in lambs, both in the presence and absence of maternal anti-RSV antibodies 38 . Efficacy of adjuvanted bovine RSV F-based vaccine candidates has been demonstrated in calves in a species homologous bovine RSV infection model 39,40 . Interestingly, human RSV F, N and M2-1 antigens expressed by a chimpanzee Adenoviral vector were immunogenic and protected calves against challenge with the heterologous bovine RSV 41 .…”