Intranasal proteosome-based respiratory syncytial virus (RSV) vaccines protect BALB/c mice against challenge without eosinophilia or enhanced pathology.
A safe and effective vaccine against respiratory syncytial virus (RSV) is still unavailable. Proteosome-based adjuvants are derived from the outer membrane proteins (OMP) of Neisseria species and are potent inducers of both mucosal and systemic immunity in humans and animals. Candidate RSV subunit vaccines comprising enriched RSV proteins (eRSV) formulated with proteosomes alone or with LPS (Protollin) were produced. Administered intranasally in BALB/c mice, both vaccines elicited long-lasting systemic and mucosal RSV-specific antibodies and fully protected against challenge. In vitro restimulation of lymphocytes from the Protollin-eRSV immunized mice with F (MHC-I) and G (MHC-II) peptides elicited F peptide-specific CD8(+) T cells and supernatant IFNgamma, TNFalpha, IL-2 and IL-10 while the formalin-inactivated RSV (FI-RSV) vaccine elicited predominantly IL-5. Pulmonary eosinophilia did not develop following immunization with either proteosome-based vaccine following challenge compared to mice immunized with FI-RSV. Proteosome-based eRSV vaccines can therefore protect against RSV challenge in mice without increasing the risk of pulmonary immunopathologic responses.
Cyr
Sonya L
SL
McGill Center for Tropical Diseases, Montreal General Hospital, Montreal, Quebec H3G IA4, Canada. sonya.l.cyr@gskbio.com
Jones
Taff
T
Stoica-Popescu
Ioana
I
Brewer
Angela
A
Chabot
Sophie
S
Lussier
Michelle
M
Burt
David
D
Ward
Brian J
BJ
D000281:Administration, Intranasal; D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis / Q000097:blood; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003546:Cysteine Endopeptidases / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D004338:Drug Combinations; D004802:Eosinophilia / Q000517:prevention & control; D005260:Female; D007371:Interferon-gamma / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology; D008168:Lung / Q000473:pathology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests; D046988:Proteasome Endopeptidase Complex / Q000276:immunology*; D018357:Respiratory Syncytial Virus Infections / Q000517:prevention & control*; D022261:Respiratory Syncytial Virus Vaccines / Q000276:immunology*; D012136:Respiratory Syncytial Viruses / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology; D022223:Vaccines, Subunit / Q000276:immunology; D014764:Viral Proteins / Q000276:immunology
D000914:Antibodies, Viral; D016207:Cytokines; D004338:Drug Combinations; D008070:Lipopolysaccharides; C493785:Protollin; D022261:Respiratory Syncytial Virus Vaccines; D022223:Vaccines, Subunit; D014764:Viral Proteins; D007371:Interferon-gamma; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex