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Teresia Maina, Elizabeth A Grego, Randy E Sacco, Balaji Narasimhan, Jodi L McGill, Mucosal delivery of a polyanhydride nanovaccine incorporating CpG and the post-fusion F/ G proteins induces protective immunity against BRSV infection in neonatal calves, The Journal of Immunology, Volume 206, Issue 1_Supplement, May 2021, Page 59.05, https://doi.org/10.4049/jimmunol.206.Supp.59.05
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Abstract
Previously, immunization with a single intranasal dose of a BRSV post-fusion F/G nanovaccine resulted in partial protection from a BRSV challenge (McGill et al. 2019, McGill et al. 2018). Knowledge gained from these previous studies was used to optimize the vaccine by incorporating CpG-ODN and to investigate the impact of mucosal vs. systemic vaccination routes. In this study a prime-boost immunization regimen was used.
36 neonatal, mixed-sex, Holstein calves were divided into 6 groups. Group 1 received a heterologous regime with saline and group 2 a homologous boost of the ‘empty’ nanovaccine CPG. Groups 3 and 4 received a homologous mucosal regime of the nanovaccine ± CpG, while groups 5 and 6 received a heterologous regime of the nanovaccine ± CpG. Vaccine-induced responses were monitored and 6 weeks after boost, all calves were challenged with BRSV. Nasopharyngeal swabs were collected for viral shedding and calves monitored for clinical signs and euthanized on day 7 after infection. Lungs were scored for gross pathology. Blood, nasal secretions and lung tissue samples were analyzed for BRSV specific immune responses.
Unvaccinated controls and CpG-only nanovaccine controls developed lung pathology consistent with a severe BRSV infection. We observed no evidence of vaccine enhanced disease in any vaccinated group. Calves that received the homologous vaccination of the nanovaccine + CPG had significantly less lung pathology and viral burden in the lungs compared to control calves.
These results indicate that an intranasal homologous vaccination regimen with the post-fusion F/G + CpG nanovaccine has the capacity to reduce BRSV disease in neonatal calves with preexisting maternal antibodies.