Use of transient CD4 lymphocyte depletion to prolong transgene expression of E1-deleted adenoviral vectors

Hum Gene Ther. 1996 Mar 1;7(4):489-97. doi: 10.1089/hum.1996.7.4-489.


E1-deleted adenoviral vectors are increasingly being utilized for in vivo gene transfer. The potential use of these vectors is limited by transient expression of the transgene and a markedly reduced rate of transduction following readministration, presumably due to a host immune response to the vector. We hypothesized that CD4+ lymphocytes are necessary to generate an immune response to these vectors and that administration of a depleting anti-CD4 antibody (GK1.5) might prolong transgene expression in vivo. We found that pretreatment of mice with a single injection (transient depletion) or weekly injections of GK1.5 (persistent depletion), markedly prolonged expression of an adenovirus-encoded tumor necrosis factor (TNF) inhibitor or luciferase gene compared to controls. Moreover, mice treated with GK1.5 showed no antiadenoviral antibody response to repeat administration of the vector and a second adenoviral transgene could be expressed in these animals. However, control mice developed a significant neutralizing antibody response that prevented transgene expression with administration of a second adenovirus. These findings demonstrate that manipulation of the host immune response may expand potential applications of gene transfer utilizing adenoviral vectors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenovirus E1 Proteins / genetics
  • Adenoviruses, Human / genetics*
  • Adenoviruses, Human / immunology
  • Animals
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / immunology
  • Antibody Formation
  • Base Sequence
  • CD4-Positive T-Lymphocytes / immunology*
  • DNA Primers
  • Gene Deletion
  • Gene Expression
  • Genetic Vectors / genetics*
  • Genetic Vectors / immunology
  • Humans
  • Liver / immunology
  • Lymphocyte Depletion
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Molecular Sequence Data
  • Recombination, Genetic
  • Time Factors
  • Transgenes*


  • Adenovirus E1 Proteins
  • Antibodies, Monoclonal
  • DNA Primers