Profiling of local disease-sparing responses to bovine respiratory syncytial virus in intranasally vaccinated and challenged calves

Abstract Bovine and human respiratory syncytial viruses (BRSV, HRSV) are primary causes of pneumonia in calves and children respectively, with vaccination offering protection via antibody and cellular immune responses. However, with no vaccines currently licensed for human use, evaluation of local responses to BRSV vaccination may provide insights to aid the design of effective safe HRSV vaccines. Calves received intranasal single component BRSV vaccine or “3-Way” vaccine (BRSV, Bovine Herpes Virus-1 (BHV-1), Bovine Parainfluenza Virus Type-3 (BPIV-3)), and were BRSV-challenged 42 days post-vaccination. All vaccinates exhibited reduced pulmonary lesioning with elevated anti-BRSV serum IgG, and higher nasal anti-BRSV IgA in 3-Way vaccinates. Thirty-nine proteins associated with homeostatic and immune processes were altered in vaccinates, with enhanced 3-Way vaccinate group proteins associated with Th1/Th2 balance and immunoglobulin class switching. Proteins altered in the pharyngeal tonsil of animals euthanized early related to anti-inflammatory responses and lymphoid tissue remodeling. These findings indicate that multivalent vaccines distinctly modulate local immune responses, with clear correlation between the pharyngeal tonsil proteome profile and resulting immune protection and disease-sparing. This suggests that the efficacy of low-antigenic subunit vaccine components for problematic pathogens such as HRSV could be enhanced by use in combination with existing safe live vaccines. Significance This study demonstrates that vaccine valency can alter post-challenge proteome responses within the pharyngeal tonsil, a sentinel site of primary immune responses, with the magnitude of response dependent on antigen formulation. Observed differential responses can be attributed to antigenic material and viral nucleic acid from multivalent formulations providing additional T-cell epitopes and PAMPS. These findings indicate that incorporation of subunits proteins within multivalent formulations containing live virus has the potential to induce/skew a favorable immune response, utilising the natural adjuvanting effects of safe proven live vaccines.