The effect of adenovirus-specific antibodies on adenoviral vector-induced, transgene product-specific T cell responses

J Leukoc Biol. 2014 Nov;96(5):821-31. doi: 10.1189/jlb.1A0813-451RR. Epub 2014 Jul 31.

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.

Keywords: AdHu5 immune serum; HIV vaccine; STEP trial; adenovirus hexon; virus neutralizing antibodies.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenoviridae / classification
  • Adenoviridae / genetics*
  • Adenoviridae / immunology*
  • Adenoviridae Infections / immunology
  • Adenoviridae Infections / prevention & control
  • Animals
  • Antibodies, Viral / immunology*
  • Antibody Specificity / immunology
  • Cross Reactions / immunology
  • Epitopes / immunology
  • Female
  • Genetic Vectors / genetics*
  • Genetic Vectors / immunology*
  • Humans
  • Immune Sera / immunology
  • Immunization, Passive
  • Immunologic Memory
  • Immunophenotyping
  • Mice
  • Phenotype
  • T-Cell Antigen Receptor Specificity / immunology
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism
  • Transduction, Genetic
  • Transgenes / immunology*
  • gag Gene Products, Human Immunodeficiency Virus / genetics
  • gag Gene Products, Human Immunodeficiency Virus / immunology

Substances

  • Antibodies, Viral
  • Epitopes
  • Immune Sera
  • gag Gene Products, Human Immunodeficiency Virus