A new subunit vaccine based on nucleoprotein nanoparticles confers partial clinical and virological protection in calves against bovine respiratory syncytial virus

Abstract

Human and bovine respiratory syncytial viruses (HRSV and BRSV) are two closely related, worldwide prevalent viruses that are the leading cause of severe airway disease in children and calves, respectively. Efficacy of commercial bovine vaccines needs improvement and no human vaccine is licensed yet. We reported that nasal vaccination with the HRSV nucleoprotein produced as recombinant ring-shaped nanoparticles (N(SRS)) protects mice against a viral challenge with HRSV. The aim of this work was to evaluate this new vaccine that uses a conserved viral antigen, in calves, natural hosts for BRSV. Calves, free of colostral or natural anti-BRSV antibodies, were vaccinated with N(SRS) either intramuscularly, or both intramuscularly and intranasally using Montanide ISA71 and IMS4132 as adjuvants and challenged with BRSV. All vaccinated calves developed anti-N antibodies in blood and nasal secretions and N-specific cellular immunity in local lymph nodes. Clinical monitoring post-challenge demonstrated moderate respiratory pathology with local lung tissue consolidations for the non-vaccinated calves that were significantly reduced in the vaccinated calves. Vaccinated calves had lower viral loads than the non-vaccinated control calves. Thus N(SRS) vaccination in calves provided cross-protective immunity against BRSV infection without adverse inflammatory reaction.

Vaccine Safety and Efficacy Evaluation of a Recombinant Bovine Respiratory Syncytial Virus (BRSV) with Deletion of the SH Gene and Subunit Vaccines Based On Recombinant Human RSV Proteins: N-nanorings, P and M2-1, in Calves with Maternal Antibodies

“…Unfortunately, we were not able to assess the local T cell immunity in SUMont-vaccinated animals, however, Riffault et al [25] demonstrated N SRS -specific IFNγ production of tracheobronchial lymph node cells in calves vaccinated with N SRS and Montanide ISA71 VG , compared to unvaccinated controls, 20 days after BRSV challenge. In further agreement with that study, serum antibodies were also induced against these proteins but were not neutralizing, and it is likely that induced mucosal IgA antibodies had similar characteristics.…”

A Novel Subnucleocapsid Nanoplatform for Mucosal Vaccination against Influenza Virus That Targets the Ectodomain of Matrix Protein 2

“…We previously documented the immunogenicity of N SRS in BALB/c mice and calves (9,10). In mice, intranasal (i.n.)…”

Purification, Stability, and Immunogenicity Analyses of Five Bluetongue Virus Proteins for Use in Development of a Subunit Vaccine That Allows Differentiation of Infected from Vaccinated Animals

“…Experimental vaccines, including disabled infectious single-cycle vaccines, virus-like particles, and subunit vaccines, rely on excluding at least one BTV protein so that detected antibodies against that protein indicate infection rather than vaccination. Thus, they are often protein based using expression systems based on viruses (13)(14)(15)(16)(17)(18), bacteria (19), yeast (20), or plants (21). To aid purification and thus reduce safety and regulatory concerns (22,23), affinity tags can be added to expressed antigens.…”