Epitopes described in "Hexon-modified recombinant E1-deleted adenovirus vectors as dual specificity vaccine carriers for influenza virus."

Article Authors:Dongming Zhou; Te-Lang Wu; Kristel L Emmer; Raj Kurupati; Steven Tuyishime; Yan Li; Wynetta Giles-Davis; Xiangyang Zhou; Zhiquan Xiang; Qin Liu; Sarah J Ratcliffe; Hildegund C J Ertl
Article Title:Hexon-modified recombinant E1-deleted adenovirus vectors as dual specificity vaccine carriers for influenza virus.
Reference Detail
Reference ID:1025578
Abstract:To determine if an ordered and repetitive display of an epitope promoted induction of superior antibody responses, we compared B-cell responses to an influenza A virus epitope that was either encoded as a transgene by an adenovirus (Ad) vector or expressed on the vector's surface. To this end, we constructed a panel of influenza A virus vaccines based on chimpanzee-derived replication-defective adenovirus (AdC) vectors of serotype SAd-V25 also called AdC68. AdC68 vectors were modified to express a linear B-cell epitope of the ectodomain of matrix 2 (M2e) within variable regions 1 (VR1) or 4 (VR4) of the adenovirus hexon. Additional vectors with wild-type or M2e-modified hexon encoded M2e fused to the influenza A virus nucleoprotein (NP) as a transgene product. Hexon-modified vectors were tested for immunogenicity and efficacy in mice in comparison to vectors with native hexon expressing the M2e-NP fusion protein. Upon priming, vectors expressing M2e within VR1 of hexon induced M2e-specific antibody responses of higher magnitude and avidity than those carrying M2e within VR4 or vectors expressing the M2e as part of a transgene product. CD8(+) T-cell responses to the transgenic NP were comparable between vectors. M2e-specific antibody responses could be boosted by a second dose of the VR1 hexon-modified vector but not by repeated immunization with the VR4 hexon-modified vector.
Affiliations:The Wistar Institute, Philadelphia, PA, USA.
Reference Type:Literature
PubMed ID:23229092
Journal:Mol Ther
Journal Volume:21
Article Pages:696-706
Journal ISSN:1525-0024
Article Chemical List:gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@219ba3d6;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@712147d6;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@3ff36ca0;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@6609d2d;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@30eef8a0;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@1904e979;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@117c13c4;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@68f5b1d3
Article MeSH List:Adenoviridae(genetics); Animals; CD8-Positive T-Lymphocytes(immunology); Epitopes, B-Lymphocyte(immunology); Genetic Therapy; Genetic Vectors; Influenza A virus(immunology); Influenza Vaccines(genetics; immunology); Mice; Mice, Inbred C57BL; Mice, Inbred ICR; RNA-Binding Proteins(genetics; immunology); Recombinant Fusion Proteins(genetics; immunology); Sensitivity and Specificity; Viral Core Proteins(genetics; immunology); Viral Matrix Proteins(genetics; immunology)
Curation Last Updated:2015-01-18 00:44:45