title: The effect of adenovirus-specific antibodies on adenoviral vector-induced, transgene product-specific T cell responses.
abstract: In this study, we tested the effect of neutralizing Abs to different serotypes of E1-deleted Ad vectors on the immunogenicity of the homologous Ad vector or a vector derived from a heterologous serotype. Our results showed that, as expected, even low titers of passively transferred neutralizing Abs significantly reduced the homologous vectors' ability to elicit transgene-specific CD8(+) T cell responses. In addition, Abs changed the fate of transgene product-specific CD8(+) T cells by promoting their transition into the central memory cell pool, which resulted in markedly enhanced expansion of transgene product-specific CD8(+) T cells after a boost with a heterologous Ad vector. Non-neutralizing Abs specific to a distinct Ad serotype had no effect on the magnitude of transgene product-specific CD8(+) T cells induced by a heterologous Ad vector, nor did such Abs promote induction of more resting memory CD8(+) T cells. These results show that Abs to an Ad vaccine carrier affect not only the magnitude but also the profile of a vector-induced CD8(+) T cell response.
authors.affiliation: The Wistar Institute, Philadelphia, Pennsylvania, USA; and Biomedical Graduate Group, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Juliana C
authors.initials: JC
authors.lastname: Small
authors.affiliation: The Wistar Institute, Philadelphia, Pennsylvania, USA; and.
authors.forename: Larissa H
authors.initials: LH
authors.lastname: Haut
authors.affiliation: The Wistar Institute, Philadelphia, Pennsylvania, USA; and.
authors.forename: Ang
authors.initials: A
authors.lastname: Bian
authors.affiliation: The Wistar Institute, Philadelphia, Pennsylvania, USA; and ertl@wistar.upenn.edu.
authors.forename: Hildegund C J
authors.initials: HC
authors.lastname: Ertl
mesh_terms: D000256:Adenoviridae / Q000145:classification / Q000235:genetics* / Q000276:immunology*; D000257:Adenoviridae Infections / Q000276:immunology / Q000517:prevention & control; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology*; D000918:Antibody Specificity / Q000276:immunology; D003429:Cross Reactions / Q000276:immunology; D000939:Epitopes / Q000276:immunology; D005260:Female; D005822:Genetic Vectors / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D007106:Immune Sera / Q000276:immunology; D007116:Immunization, Passive; D007156:Immunologic Memory; D016130:Immunophenotyping; D051379:Mice; D010641:Phenotype; D037182:T-Cell Antigen Receptor Specificity / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D014161:Transduction, Genetic; D019076:Transgenes / Q000276:immunology*; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D000939:Epitopes; D007106:Immune Sera; D054301:gag Gene Products, Human Immunodeficiency Virus
keywords: AdHu5 immune serum; HIV vaccine; STEP trial; adenovirus hexon; virus neutralizing antibodies
references.citation: J Immunol. 1976 Jan;116(1):25-9
references.pmid: 54389
references.citation: J Immunol. 2005 Sep 15;175(6):3502-7
references.pmid: 16148092
references.citation: Nature. 2011 May 26;473(7348):523-7
references.pmid: 21562493
references.citation: Lancet. 2008 Nov 29;372(9653):1894-1905
references.pmid: 19012957
references.citation: J Exp Med. 2008 Nov 24;205(12):2717-25
references.pmid: 18981239
references.citation: Curr Top Microbiol Immunol. 2000;251:167-71
references.pmid: 11036772
references.citation: J Virol. 2002 Nov;76(21):10608-16
references.pmid: 12368303
references.citation: J Immunol. 2005 Nov 1;175(9):6032-41
references.pmid: 16237098
references.citation: Nat Protoc. 2010 Nov;5(11):1775-1785
references.pmid: 21030953
references.citation: Blood. 2007 Sep 15;110(6):1916-23
references.pmid: 17510320
references.citation: J Virol. 2002 Mar;76(6):2667-75
references.pmid: 11861833
references.citation: Virology. 2003 Jul 5;311(2):384-93
references.pmid: 12842627
references.citation: Nature. 2002 Jan 17;415(6869):331-5
references.pmid: 11797011
references.citation: J Virol. 2007 Jun;81(12):6594-604
references.pmid: 17428852
references.citation: Mol Ther. 2009 Aug;17(8):1333-9
references.pmid: 19513019
references.citation: Proc Natl Acad Sci U S A. 2009 Nov 24;106(47):19940-5
references.pmid: 19918060
references.citation: Emerg Infect Dis. 2006 Oct;12(10):1596-9
references.pmid: 17176582
references.citation: Vaccine. 2011 Jul 18;29(32):5203-9
references.pmid: 21619905
references.citation: J Immunol. 2005 Oct 1;175(7):4677-85
references.pmid: 16177115
references.citation: Nat Immunol. 2003 Dec;4(12):1191-8
references.pmid: 14625547
references.citation: AIDS Res Hum Retroviruses. 2009 Jan;25(1):103-14
references.pmid: 19108693
references.citation: J Exp Med. 2008 Mar 17;205(3):625-40
references.pmid: 18316415
references.citation: J Immunol. 2010 Jul 1;185(1):263-72
references.pmid: 20519649
references.citation: J Virol. 1995 Apr;69(4):2004-15
references.pmid: 7884845
references.citation: Lancet. 2008 Nov 29;372(9653):1881-1893
references.pmid: 19012954
references.citation: J Virol. 2004 Mar;78(6):2666-73
references.pmid: 14990686
references.citation: Eur J Immunol. 2010 Dec;40(12):3426-38
references.pmid: 21108465
references.citation: J Infect Dis. 2013 Jan 15;207(2):248-56
references.pmid: 23125443
references.citation: J Virol. 2010 Oct;84(20):10522-32
references.pmid: 20686035