Humoral and cellular immune responses of nonhuman primates to long-term repeated lung exposure to Ad2/CFTR-2

Gene Ther. 1996 Feb;3(2):117-27.


To evaluate the host immune response to long-term repeat administration of adenovirus vector, rhesus monkeys were treated at intervals of approximately 3 weeks with up to 18 instillations of Ad2/CFTR-2, a second generation vector encoding the cystic fibrosis transmembrane conductance regulator (CFTR). All monkeys instilled with Ad2/CFTR-2 developed a significant humoral immune response against adenovirus but not CFTR. Antibodies with virus neutralizing activity were detected in the serum and bronchoalveolar lavage (BAL) of all vector-treated monkeys and included both IgG and secretory IgA. Virus-specific T cells capable of proliferating in response to stimulation with adenovirus antigen were detected in all vector-treated monkeys. No CFTR-specific proliferation of peripheral blood lymphocytes was detected. An increase in the proportion of CD8+ T cells was noted in the BAL of virus-treated monkeys but cells from the BAL displayed little or no cytolytic activity against infected autologous fibroblasts when tested under a variety of culture conditions. However, MHC-restricted cytolytic activity was detected in the tracheobronchial lymph nodes and spleen of one of three virus-treated monkeys tested. MHC-unrestricted killing of infected fibroblasts was also observed with spleen cells from all animals tested. From these results, it appears that both the humoral and cell-mediated arms of the immune response were stimulated by repeated administration of high doses of Ad2/CFTR-2 suggesting that effective, long-term adenovirus gene therapy may require modification of the vector or treatment of the host to allow the virus to evade host immune defenses.

Publication types

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

MeSH terms

  • Adenoviruses, Human / genetics
  • Adenoviruses, Human / immunology*
  • Animals
  • Antibodies, Viral / analysis*
  • Antibodies, Viral / blood
  • Antigens, CD / analysis
  • Bronchoalveolar Lavage Fluid / immunology
  • Cystic Fibrosis / immunology
  • Cystic Fibrosis / therapy
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics*
  • Cytotoxicity, Immunologic / immunology*
  • Dose-Response Relationship, Drug
  • Genetic Therapy / methods
  • Genetic Vectors / administration & dosage
  • Genetic Vectors / immunology*
  • Immunoglobulin A / analysis
  • Lymph Nodes / immunology
  • Lymphocyte Activation
  • Macaca mulatta
  • Neutralization Tests
  • Spleen / immunology
  • T-Lymphocytes / immunology


  • Antibodies, Viral
  • Antigens, CD
  • Immunoglobulin A
  • Cystic Fibrosis Transmembrane Conductance Regulator