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ARS Home » Midwest Area » Ames, Iowa » National Animal Disease Center » Ruminant Diseases and Immunology Research » Research » Publications at this Location » Publication #399787

Research Project: Intervention Strategies to Prevent and Control Viral Respiratory Pathogens of Ruminants

Location: Ruminant Diseases and Immunology Research

Title: Immunization with a mucosal, post-fusion F/G protein-based polyanhydride nanovaccine protects neonatal calves against BRSV infection

item MAINA, TERESIA - Iowa State University
item GREGO, ELIZABETH - Iowa State University
item BRODERICK, SCOTT - University At Buffalo
item Sacco, Randy
item NARASIMHAN, BALAJI - Iowa State University
item MCGILL, JODI - Iowa State University

Submitted to: Frontiers in Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/25/2023
Publication Date: 6/9/2023
Citation: Maina, T.W., Grego, E.A., Broderick, S., Sacco, R.E., Narasimhan, B., Mcgill, J.L. 2023. Immunization with a mucosal, post-fusion F/G protein-based polyanhydride nanovaccine protects neonatal calves against BRSV infection. Frontiers in Immunology. 14. Article 1186184.

Interpretive Summary: In this manuscript, we have developed and tested a new vaccine for a respiratory virus in calves. The disease in calves closely mimics that in humans with a related respiratory virus, so the studies conducted provide data that will also be useful in developing a new vaccine for use in humans. The vaccine developed uses a new method for delivery of proteins from the virus. The proteins are enclosed in small particles that can be delivered into the nasal passages. Our work shows that the vaccine induced an appropriate immune response and provided significant protection to the calves following exposure to the live virus. This work will be of interest to those studying respiratory infections and those developing new vaccines against these infections.

Technical Abstract: Human respiratory syncytial virus (HRSV) has a significant negative impact on the respiratory health of infants and young children. Although RSV is one of the leading causes of death in children under one year old, there are currently no FDA approved vaccines available. Bovine RSV (BRSV) is genetically and antigenically similar to HRSV, and the neonatal calf model is useful for evaluation of candidate HRSV vaccines. Here, in two independent trials, we evaluated the efficacy and immunogenicity of a polyanhydride-based nanovaccine encapsulating the BRSV post-fusion F and G glycoproteins and CpG, delivered via heterologous (intranasal/subcutaneous) or homologous (intranasal/intranasal) prime-boost in the neonatal calf model. We compared their performance to a parenterally administered, commercial modified live vaccine, and to nonvaccinated control calves. Calves receiving either nanovaccine regimen exhibited reduced clinical disease scores and less viral replication in nasal samples and lung tissues compared to nonvaccinated calves. The intranasal/subcutaneous nanovaccine regimen induced both virus-specific cellular immunity and mucosal IgA. Principal component analysis of immune parameters identified BRSV-specific serum neutralizing antibodies, nasal IgA and cellular responses as important correlates of protection. With optimization, the BRSV-F/G CpG nanovaccine has the potential to reduce RSV disease burden in both humans and animals.