Characterization of an experimental vaccine for bovine respiratory syncytial virus.
Bovine respiratory syncytial virus (BRSV) and human respiratory syncytial virus (HRSV) are major causes of respiratory disease in calves and children, respectively, and are priorities for vaccine development. We previously demonstrated that an experimental vaccine, BRSV-immunostimulating complex (ISCOM), is effective in calves with maternal antibodies. The present study focuses on the antigenic characterization of this vaccine for the design of new-generation subunit vaccines. The results of our study confirmed the presence of membrane glycoprotein (G), fusion glycoprotein (F), and nucleoprotein (N) proteins in the ISCOMs, and this knowledge was extended by the identification of matrix (M), M2-1, phosphoprotein (P), small hydrophobic protein (SH) and of cellular membrane proteins, such as the integrins αVβ1, αVβ3, and α3β1. The quantity of the major protein F was 4- to 5-fold greater than that of N (∼77 μg versus ∼17 μg/calf dose), whereas G, M, M2-1, P, and SH were likely present in smaller amounts. The polymerase (L), M2-2, nonstructural 1 (NS1), and NS2 proteins were not detected, suggesting that they are not essential for protection. Sera from the BRSV-ISCOM-immunized calves contained high titers of IgG antibody specific for F, G, N, and SH. Antibody responses against M and P were not detected; however, this does not exclude their role in protective T-cell responses. The absence of immunopathological effects of the cellular proteins, such as integrins, needs to be further confirmed, and their possible contribution to adjuvant functions requires elucidation. This work suggests that a combination of several surface and internal proteins should be included in subunit RSV vaccines and identifies absent proteins as potential candidates for differentiating infected from vaccinated animals.
Swedish University of Agricultural Sciences, Host Pathogen Interaction Group, Department of Clinical Sciences, Uppsala, Sweden sara.hagglund@slu.se.
Sara
S
Hägglund
Swedish University of Agricultural Sciences, Host Pathogen Interaction Group, Department of Clinical Sciences, Uppsala, Sweden.
Kefei
K
Hu
Swedish University of Agricultural Sciences, Host Pathogen Interaction Group, Department of Clinical Sciences, Uppsala, Sweden.
Krister
K
Blodörn
The Pirbright Institute, Pirbright, Surrey, United Kingdom.
Boby
B
Makabi-Panzu
INRA, Unité de Virologie et Immunologie Moléculaires, Jouy-en-Josas, France.
Anne-Laure
AL
Gaillard
Swedish University of Agricultural Sciences, Host Pathogen Interaction Group, Department of Clinical Sciences, Uppsala, Sweden.
Karin
K
Ellencrona
INRA, UMR1319 Micalis, Plateforme d'Analyse Protéomique de Paris Sud-Ouest, Jouy-en-Josas, France.
Didier
D
Chevret
Uppsala University, Department of Cell and Molecular Biology, Chemical Biology, Uppsala, Sweden.
Lars
L
Hellman
Novavax AB, Uppsala, Sweden.
Karin Lövgren
KL
Bengtsson
INRA, Unité de Virologie et Immunologie Moléculaires, Jouy-en-Josas, France.
Sabine
S
Riffault
The Pirbright Institute, Pirbright, Surrey, United Kingdom.
Geraldine
G
Taylor
Swedish University of Agricultural Sciences, Host Pathogen Interaction Group, Department of Clinical Sciences, Uppsala, Sweden National Veterinary Institute, Department of Virology, Immunobiology and Parasitology, Uppsala, Sweden.
Jean François
JF
Valarcher
INRA, Unité de Virologie et Immunologie Moléculaires, Jouy-en-Josas, France.
Jean-François
JF
Eléouët
D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology*; D000917:Antibody Formation; D002417:Cattle; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D016023:Integrins / Q000276:immunology; D008562:Membrane Glycoproteins / Q000276:immunology; D009698:Nucleoproteins / Q000276:immunology; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology / Q000517:prevention & control*; D022261:Respiratory Syncytial Virus Vaccines / Q000276:immunology*; D018112:Respiratory Syncytial Virus, Bovine / Q000276:immunology* / Q000472:pathogenicity; D018113:Respiratory Syncytial Virus, Human / Q000276:immunology / Q000472:pathogenicity; D014611:Vaccination; D022223:Vaccines, Subunit / Q000276:immunology*; D014760:Viral Fusion Proteins / Q000276:immunology
D000914:Antibodies, Viral; D007074:Immunoglobulin G; D016023:Integrins; D008562:Membrane Glycoproteins; D009698:Nucleoproteins; D022261:Respiratory Syncytial Virus Vaccines; D022223:Vaccines, Subunit; D014760:Viral Fusion Proteins