title: A recombinant subunit vaccine for bovine RSV and Histophilus somni protects calves against dual pathogen challenge.
abstract: Bovine respiratory syncytial virus (BRSV) and Histophilus somni synergize to cause respiratory disease in cattle. These pathogens cause enhanced disease during dual-infection and an IgE response to antigens of H. somni in dual-infected but not singly infected calves. Vaccines containing whole inactivated BRSV or H. somni have been associated with IgE responses A vaccine strategy that avoids stimulation of IgE antibodies would provide superior protection from dual infection. We hypothesized that a subunit vaccine consisting of the nucleoprotein (NP) from BRSV and the recombinant antigen IbpA DR2 (a surface antigen of H. somni with two toxic fic motifs) in Quil A adjuvant would elicit protection without disease enhancement. Three groups of calves were vaccinated twice with either: Formalin inactivated BRSV (FI) plus Somnivac®, NP & IbpA DR2 plus Quil A or Quil A alone, followed by BRSV and H. somni challenge. Clinical scores and antibody levels (to whole pathogens and to the subunits) were evaluated. Lungs were examined at necropsy on day 23 after infection. Clinical scores were significantly greatest for the FI & Somnivac® group and both clinical scores and lung pathology were lowest for the subunit group. All calves shed BRSV in nasal secretions. FI & Somnivac® induced IgE antibodies to H. somni and BRSV, but not to NP or DR2. The subunit vaccine did not induce an IgE antibody response to IbpA DR2 antigen and induced little IgE to H. somni. It did not induce an IgG antibody response to BRSV and H. somni, but stimulated production of IgG antibodies against the subunits. In summary, the subunit vaccine, consisting of the BRSV NP and H. somni IbpA DR2 in Quil A, protected against severe clinical signs and decreased lung pathology but did not prevent viral shedding. Importantly it prevented synergistic disease expression in response to dual infection.
authors.affiliation: Department of Pathology, Microbiology, & Immunology, School of Veterinary Medicine, University of California, Davis, United States. Electronic address: ljgershwin@ucdavis.edu.
authors.forename: Laurel J
authors.initials: LJ
authors.lastname: Gershwin
authors.affiliation: Department of Pathology, Microbiology, & Immunology, School of Veterinary Medicine, University of California, Davis, United States.
authors.forename: Nicole E
authors.initials: NE
authors.lastname: Behrens
authors.affiliation: Department of Pathology, Microbiology, & Immunology, School of Veterinary Medicine, University of California, Davis, United States.
authors.forename: Heather A
authors.initials: HA
authors.lastname: McEligot
authors.affiliation: Department of Pathology, Microbiology, & Immunology, School of Veterinary Medicine, University of California, Davis, United States.
authors.forename: Francisco R
authors.initials: FR
authors.lastname: Carvallo-Chaigneau
authors.affiliation: Department of Pathology, School of Medicine, University of California, San Diego, United States.
authors.forename: Lauren T
authors.initials: LT
authors.lastname: Crum
authors.affiliation: Department of Pathology, Microbiology, & Immunology, School of Veterinary Medicine, University of California, Davis, United States.
authors.forename: Brianna M
authors.initials: BM
authors.lastname: Gunnarson
authors.affiliation: Department of Pathology, School of Medicine, University of California, San Diego, United States.
authors.forename: Lynette B
authors.initials: LB
authors.lastname: Corbeil
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D000917:Antibody Formation; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D002417:Cattle; D008168:Lung / Q000473:pathology; D015661:Pasteurellaceae / Q000276:immunology*; D016871:Pasteurellaceae Infections / Q000473:pathology / Q000517:prevention & control / Q000662:veterinary*; D062605:Quillaja Saponins / Q000008:administration & dosage; D018357:Respiratory Syncytial Virus Infections / Q000517:prevention & control / Q000662:veterinary*; D012136:Respiratory Syncytial Viruses / Q000276:immunology*; D012720:Severity of Illness Index; D016896:Treatment Outcome; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D001428:Bacterial Vaccines; D062605:Quillaja Saponins; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic; D014765:Viral Vaccines; C046386:Quil A
keywords: BRSV; Histophilus somni; IgE; Nucleoprotein; Subunit; Vaccine