The development of adjuvants will represent a major challenge for this century. Indeed the need for safer vaccines leads to the development of a new generation of antigens like synthetic peptide, recombinant proteins or even vectored DNA. However, this is to the detriment of their immunogenicity. The addition of adjuvant is becomes necessary to enhance immune responses and improve vaccine potency. However, adjuvants can be responsible for the apparition of secondary reactions and they must be adapted according to various criteria such as the route of immunization, the type of the immune response, the duration of immunity, or the quality of the antigen, in order to get the best balance between efficacy and safety.

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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.

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