title: Expression of human rotavirus chimeric fusion proteins from replicating but non disseminating adenovectors and elicitation of rotavirus-specific immune responses in mice.
abstract: The aim of this study was to evaluate the usefulness of replicating but non disseminating adenovirus vectors (AdVs) as vaccine vector using human rotavirus (HRV) as a model pathogen. HRV VP7, VP4, or VP4Δ (N-terminal 336 amino acids of VP4) structural proteins as well as the VP4Δ::VP7 chimeric fusion protein were expressed in mammalian cells when delivered with the AdVs. A preliminary experiment demonstrated that VP4Δ was able to induce a HRV-specific IgG response in BALB/c mice inoculated intramuscularly with AdVs expressing the rotaviral protein. Moreover, an AdV-prime/plasmid DNA-boost regimen of vectors resulted in VP4Δ-specific antibody (Ab) titers ~4 times higher than those obtained from mice immunized with AdVs alone. Subsequently, the various HRV protein-encoding AdVs were compared using the AdV-prime/plasmid DNA-boost regimen. Higher IgG and IgA responses to HRV were obtained when VP4Δ::VP7 fusion protein was used as an immunogen as compared to VP7 or VP4 alone or to a mix of both proteins delivered independently by AdVs. A synergetic effect in terms of Ab was obtained with VP4Δ::VP7. In conclusion, this study demonstrated for the first time the suitability of using replicating but non disseminating AdVs as vaccine vector and the VP4Δ::VP7 fusion protein as an immunogen for vaccination against HRV.
authors: Department of Biological Sciences, University of Quebec at Montreal, P.O. Box 8888, Succursale Centre-Ville, Montréal, Québec, H3C 3P8, Canada.
authors: Aurélie
authors: A
authors: Girard
authors: Elodie
authors: E
authors: Roques
authors: Marie-Claude
authors: MC
authors: St-Louis
authors: Bernard
authors: B
authors: Massie
authors: Denis
authors: D
authors: Archambault
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000704:Analysis of Variance; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood / Q000276:immunology; D000956:Antigens, Viral / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D036022:Capsid Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D045744:Cell Line, Tumor; D005260:Female; D005822:Genetic Vectors / Q000235:genetics*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D012401:Rotavirus / Q000235:genetics / Q000276:immunology*; D012400:Rotavirus Infections / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D022243:Rotavirus Vaccines / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D014162:Transfection
chemical_list: D057134:Antibodies, Neutralizing; D000956:Antigens, Viral; D036022:Capsid Proteins; D011993:Recombinant Fusion Proteins; D022243:Rotavirus Vaccines; C060339:VP4 protein, Rotavirus; C050779:VP7 protein, Rotavirus