Interactions between human plasma components and a xenogenic adenovirus vector: reduced immunogenicity during gene transfer

Mol Ther. 2007 Nov;15(11):1998-2007. doi: 10.1038/ Epub 2007 Aug 21.


By the time we are adolescents most of us have been in contact with several of the >50 human adenovirus (HAd) serotypes. These common subclinical infections lead to an efficient anti-adenovirus cross-reacting adaptive immunity. During gene therapy, the ubiquitous anti-adenovirus humoral response and complement activation will modify and dictate vector biodistribution, as well as the response to the virion and transgene(s). In this study, we assayed the interactions of a xenogenic adenovirus derived from canine serotype 2 (CAV-2) with naturally occurring human antibodies (Abs) and the complement system. In our cohort, we found class G immunoglobulins (Igs) that recognized the intact CAV-2 virion and the external virion proteins. However, the majority of donors had low or no neutralizing Abs, class A, or class M Igs. Purified anti-HAd serotype 5 Abs also recognized CAV-2 virion proteins. In addition, in spite of the presence of anti-CAV-2 IgGs, CAV-2 poorly activated the classical and alternative complement cascades. This atypical response was due to a block upstream of the component 3 (C3) convertase and interplay between the component 1 (C1) inhibitor, the C1q-C1r2-C1s2 complex and CAV-2. Our data demonstrate that some xenogenic adenovirus vectors, like CAV-2, could lead to notably different outcomes following systemic delivery.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics*
  • Adenoviridae / immunology*
  • Antibody Formation / immunology
  • Blood Proteins / immunology*
  • Blood Proteins / metabolism*
  • Cross Reactions
  • Genetic Vectors / genetics*
  • Genetic Vectors / immunology*
  • Humans
  • Immunogenetics*
  • Immunoglobulin G / immunology
  • Plant Lectins / metabolism
  • Ribosome Inactivating Proteins / metabolism
  • Signal Transduction
  • Transduction, Genetic*


  • Blood Proteins
  • Immunoglobulin G
  • Plant Lectins
  • Sambucus nigra lectins
  • Ribosome Inactivating Proteins