Expression of human rotavirus chimeric fusion proteins from replicating but non disseminating adenovectors and elicitation of rotavirus-specific immune responses in mice

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DOIResolve DOI: http://doi.org/10.1007/s12033-013-9653-9
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TypeArticle
Journal titleMolecular Biotechnology
ISSN1073-6085
Volume54
Issue3
Pages10101020; # of pages: 11
SubjectImmunogenicity; Neutralizing antibodies; Replicating but non disseminating adenovectors; Rotaviruses; VP4; VP7; Amino acids; Antibodies; Vaccines; Vectors; Viruses; Mammals; adenovirus vector; chimeric protein; immunoglobulin A; immunoglobulin G; plasmid DNA; protein VP4; protein VP7; virus fusion protein; animal experiment; article; controlled study; female; human; human cell; Human rotavirus; immune response; immunogenicity; lymphocyte; lymphocyte proliferation; mammal cell; mouse; nonhuman; nucleotide sequence; protein expression; virus expression; Adenoviridae; Analysis of Variance; Animals; Antibodies, Neutralizing; Antigens, Viral; Capsid Proteins; Cell Line, Tumor; Female; Genetic Vectors; Humans; Mice; Mice, Inbred BALB C; Recombinant Fusion Proteins; Rotavirus; Rotavirus Infections; Rotavirus Vaccines; Transfection; Adenoviridae; Human rotavirus A; Mammalia; Mus; Rotavirus
AbstractThe 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. © 2013 Springer Science+Business Media New York.
Publication date
LanguageEnglish
AffiliationNational Research Council Canada (NRC-CNRC)
Peer reviewedYes
NPARC number21270683
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Record identifiera90ed368-b8c5-4901-bb19-655a1fb26f74
Record created2014-02-17
Record modified2016-05-09
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