title: Effect of preexisting immunity on an adenovirus vaccine vector: in vitro neutralization assays fail to predict inhibition by antiviral antibody in vivo.
abstract: A major obstacle to the use of adenovirus vectors derived from common human serotypes, such as human adenovirus 5 (AdHu5), is the high prevalence of virus-neutralizing antibodies in the human population. We previously constructed a variant of chimpanzee adenovirus 68 (AdC68) that maintained the fundamental properties of the carrier but was serologically distinct from AdC68 and resisted neutralization by AdC68 antibodies. In the present study, we tested whether this modified vector, termed AdCDQ, could induce transgene product-specific CD8(+) T cells in mice with preexisting neutralizing antibody to wild-type AdC68. Contrary to our expectation, the data show conclusively that antibodies that fail to neutralize the AdCDQ mutant vector in vitro nevertheless impair the vector's capacity to transduce cells and to stimulate a transgene product-specific CD8(+) T-cell response in vivo. The results thus suggest that in vitro neutralization assays may not reliably predict the effects of virus-specific antibodies on adenovirus vectors in vivo.
authors.affiliation: Division of Infectious Diseases, the Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA. susan.l.gollon@gsk.com
authors.forename: Susan L
authors.initials: SL
authors.lastname: Pichla-Gollon
authors.forename: Shih-Wen
authors.initials: SW
authors.lastname: Lin
authors.forename: Scott E
authors.initials: SE
authors.lastname: Hensley
authors.forename: Marcio O
authors.initials: MO
authors.lastname: Lasaro
authors.forename: Larissa
authors.initials: L
authors.lastname: Herkenhoff-Haut
authors.forename: Mark
authors.initials: M
authors.lastname: Drinker
authors.forename: Nia
authors.initials: N
authors.lastname: Tatsis
authors.forename: Guang-Ping
authors.initials: GP
authors.lastname: Gao
authors.forename: James M
authors.initials: JM
authors.lastname: Wilson
authors.forename: Hildegund C J
authors.initials: HC
authors.lastname: Ertl
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Bergelson
mesh_terms: D000256:Adenoviridae / Q000235:genetics* / Q000276:immunology*; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology* / Q000494:pharmacology*; D000918:Antibody Specificity; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D017930:Genes, Reporter / Q000235:genetics; D005822:Genetic Vectors / Q000235:genetics* / Q000276:immunology*; D007118:Immunoassay; D051379:Mice; D008807:Mice, Inbred BALB C; D011961:Receptors, Fc / Q000276:immunology; D019076:Transgenes / Q000235:genetics; D014765:Viral Vaccines / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D011961:Receptors, Fc; D014765:Viral Vaccines