title: 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.
abstract: The development of safe and effective vaccines against both bovine and human respiratory syncytial viruses (BRSV, HRSV) to be used in the presence of RSV-specific maternally-derived antibodies (MDA) remains a high priority in human and veterinary medicine. Herein, we present safety and efficacy results from a virulent BRSV challenge of calves with MDA, which were immunized with one of three vaccine candidates that allow serological differentiation of infected from vaccinated animals (DIVA): an SH gene-deleted recombinant BRSV (ΔSHrBRSV), and two subunit (SU) formulations based on HRSV-P, -M2-1, and -N recombinant proteins displaying BRSV-F and -G epitopes, adjuvanted by either oil emulsion (Montanide ISA71VG, SUMont) or immunostimulating complex matrices (AbISCO-300, SUAbis). Whereas all control animals developed severe respiratory disease and shed high levels of virus following BRSV challenge, ΔSHrBRSV-immunized calves demonstrated almost complete clinical and virological protection five weeks after a single intranasal vaccination. Although mucosal vaccination with ΔSHrBRSV failed to induce a detectable immunological response, there was a rapid and strong anamnestic mucosal BRSV-specific IgA, virus neutralizing antibody and local T cell response following challenge with virulent BRSV. Calves immunized twice intramuscularly, three weeks apart with SUMont were also well protected two weeks after boost. The protection was not as pronounced as that in ΔSHrBRSV-immunized animals, but superior to those immunized twice subcutaneously three weeks apart with SUAbis. Antibody responses induced by the subunit vaccines were non-neutralizing and not directed against BRSV F or G proteins. When formulated as SUMont but not as SUAbis, the HRSV N, P and M2-1 proteins induced strong systemic cross-protective cell-mediated immune responses detectable already after priming. ΔSHrBRSV and SUMont are two promising DIVA-compatible vaccines, apparently inducing protection by different immune responses that were influenced by vaccine-composition, immunization route and regimen.
authors.affiliation: Swedish University of Agricultural Sciences, Host Pathogen Interaction Group, Department of Clinical Sciences, Uppsala, Sweden.
authors.forename: Krister
authors.initials: K
authors.lastname: Blodörn
authors.affiliation: Swedish University of Agricultural Sciences, Host Pathogen Interaction Group, Department of Clinical Sciences, Uppsala, Sweden.
authors.forename: Sara
authors.initials: S
authors.lastname: Hägglund
authors.affiliation: INRA, Unité de Virologie et Immunologie Moléculaires, Jouy-en-Josas, France.
authors.forename: Jenna
authors.initials: J
authors.lastname: Fix
authors.affiliation: INRA, Unité de Virologie et Immunologie Moléculaires, Jouy-en-Josas, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Dubuquoy
authors.affiliation: The Pirbright Institute, Pirbright, Surrey, United Kingdom.
authors.forename: Boby
authors.initials: B
authors.lastname: Makabi-Panzu
authors.affiliation: The Pirbright Institute, Pirbright, Surrey, United Kingdom.
authors.forename: Michelle
authors.initials: M
authors.lastname: Thom
authors.affiliation: National Veterinary Institute, Department of Virology, Immunology, and Parasitology, Uppsala, Sweden.
authors.forename: Per
authors.initials: P
authors.lastname: Karlsson
authors.affiliation: Clinique Veterinaire des Mazets, Riom es Montagnes, France.
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Roque
authors.affiliation: National Veterinary Institute, Department of Pathology and Wildlife Diseases, Uppsala, Sweden.
authors.forename: Erika
authors.initials: E
authors.lastname: Karlstam
authors.affiliation: Swedish University of Agricultural Sciences, Host Pathogen Interaction Group, Department of Clinical Sciences, Uppsala, Sweden.
authors.forename: John
authors.initials: J
authors.lastname: Pringle
authors.affiliation: INRA, Unité de Virologie et Immunologie Moléculaires, Jouy-en-Josas, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Eléouët
authors.affiliation: INRA, Unité de Virologie et Immunologie Moléculaires, Jouy-en-Josas, France.
authors.forename: Sabine
authors.initials: S
authors.lastname: Riffault
authors.affiliation: The Pirbright Institute, Pirbright, Surrey, United Kingdom.
authors.forename: Geraldine
authors.initials: G
authors.lastname: Taylor
authors.affiliation: Swedish University of Agricultural Sciences, Host Pathogen Interaction Group, Department of Clinical Sciences, Uppsala, Sweden; National Veterinary Institute, Department of Virology, Immunology, and Parasitology, Uppsala, Sweden.
authors.forename: Jean François
authors.initials: JF
authors.lastname: Valarcher
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology*; D002417:Cattle; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D017353:Gene Deletion; D005814:Genes, Viral; D006801:Humans; D008168:Lung / Q000276:immunology / Q000473:pathology / Q000821:virology; D008198:Lymph Nodes / Q000473:pathology; D008214:Lymphocytes / Q000276:immunology; D008969:Molecular Sequence Data; D018357:Respiratory Syncytial Virus Infections / Q000097:blood / Q000276:immunology / Q000821:virology; D022261:Respiratory Syncytial Virus Vaccines / Q000009:adverse effects* / Q000276:immunology; D018112:Respiratory Syncytial Virus, Bovine / Q000235:genetics* / Q000276:immunology* / Q000472:pathogenicity; D018113:Respiratory Syncytial Virus, Human / Q000276:immunology / Q000378:metabolism*; D013045:Species Specificity; D014611:Vaccination; D022223:Vaccines, Subunit / Q000009:adverse effects / Q000276:immunology; D019562:Viral Load; D014764:Viral Proteins / Q000378:metabolism*; D014774:Virulence
chemical_list: D000914:Antibodies, Viral; D000939:Epitopes; D022261:Respiratory Syncytial Virus Vaccines; D022223:Vaccines, Subunit; D014764:Viral Proteins