Novel Adenovirus type 5 vaccine platform induces cellular immunity against HIV-1 Gag, Pol, Nef despite the presence of Ad5 immunity

Vaccine. 2009 Oct 30;27(46):6394-8. doi: 10.1016/j.vaccine.2009.06.028. Epub 2009 Jun 24.

Abstract

Recombinant Adenovirus serotype 5 (Ad5) vectors have been used as vaccine platforms in numerous animal and human clinical studies. The immune response induced by Ad5 vaccines can be mitigated due to pre-existing Ad5 immunity. We previously reported the use of a novel Ad5 platform to induce cellular immune responses (CMI) against HIV-1 Gag in Ad5 hyper immune mice. Here, the effectiveness of the Ad5 [E1-, E2b-] vaccine platform was evaluated using a triad mixture of HIV-1 Gag, Pol, and Nef as antigenic transgenes. Broad CMI was induced following vaccination with the HIV-1 expressing vectors in Ad5 naïve and Ad5 immunized mice. A mixture of the three vaccines induced CMI against each transgene product even in the presence of hyper Ad5 immunity. These studies revealed that CMI responses to immunization with Ad5 [E1-, E2b-]-gag, Ad5 [E1-, E2b-]-pol or Ad5 [E1-, E2b-]-nef vectors were transgene specific and did not induce CMI responses against irrelevant antigens such as carcinoembryonic antigen (CEA), herpes simplex virus glycoprotein B (HSV), cytomegalovirus (CMV) or influenza virus antigens. We are evaluating this recombinant triad viral vector as an HIV-1 vaccine in a non-human primate model and the data indicate that the vaccine is worthy of clinical evaluation.

Publication types

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

MeSH terms

  • AIDS Vaccines / immunology*
  • Adenoviridae / immunology*
  • Animals
  • Female
  • Genetic Vectors
  • HIV Infections / immunology
  • HIV Infections / prevention & control*
  • HIV-1 / immunology
  • Immunity, Cellular*
  • Interferon-gamma / immunology
  • Mice
  • Mice, Inbred BALB C
  • Neutralization Tests
  • Spleen / cytology
  • Spleen / immunology
  • Transgenes
  • Vaccines, Synthetic / immunology
  • gag Gene Products, Human Immunodeficiency Virus / immunology
  • nef Gene Products, Human Immunodeficiency Virus / immunology
  • pol Gene Products, Human Immunodeficiency Virus / immunology

Substances

  • AIDS Vaccines
  • Vaccines, Synthetic
  • gag Gene Products, Human Immunodeficiency Virus
  • nef Gene Products, Human Immunodeficiency Virus
  • nef protein, Human immunodeficiency virus 1
  • pol Gene Products, Human Immunodeficiency Virus
  • Interferon-gamma