GM-CSF DNA: An Adjuvant for Higher Avidity IgG, Rectal IgA, and Increased Protection Against the Acute Phase of a SHIV-89.6P Challenge by a DNA/MVA Immunodeficiency Virus Vaccine

Virology. 2007 Dec 5;369(1):153-67. doi: 10.1016/j.virol.2007.07.017. Epub 2007 Aug 14.

Abstract

Single intradermal or intramuscular inoculations of GM-CSF DNA with the DNA prime for a simian-human immunodeficiency virus (SHIV)-89.6 vaccine, which consists of DNA priming followed by modified vaccinia Ankara (MVA) boosting, increased protection of both the blood and intestines against the acute phase of an intrarectal SHIV-89.6P challenge. GM-CSF appeared to contribute to protection by enhancing two antibody responses: the avidity maturation of anti-Env IgG in blood (p=or<0.01) and the presence of long lasting anti-viral IgA in rectal secretions (p<0.01). The avidity of anti-Env IgG showed strong correlations with protection both pre and post challenge. Animals with the highest avidity anti-Env Ab had 1000-fold reductions in peak viremia over those with the lowest avidity anti-Env Ab. The enhanced IgA response was associated with the best protection, but did not achieve significance.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS Vaccines / genetics
  • AIDS Vaccines / immunology*
  • Adjuvants, Immunologic / administration & dosage*
  • Adjuvants, Immunologic / genetics
  • Animals
  • Antibodies, Viral / immunology*
  • Antibody Affinity / immunology
  • Granulocyte-Macrophage Colony-Stimulating Factor / genetics
  • Granulocyte-Macrophage Colony-Stimulating Factor / immunology*
  • Immunization, Secondary
  • Immunoglobulin A / analysis
  • Immunoglobulin A / immunology
  • Immunoglobulin G / blood
  • Immunoglobulin G / immunology
  • Injections, Intradermal
  • Injections, Intramuscular
  • Macaca mulatta
  • Rectum / immunology*
  • SAIDS Vaccines / genetics
  • SAIDS Vaccines / immunology*
  • Simian Acquired Immunodeficiency Syndrome / drug therapy
  • Simian Acquired Immunodeficiency Syndrome / prevention & control
  • Vaccines, DNA / genetics
  • Vaccines, DNA / immunology*
  • Vaccinia virus / genetics
  • Vaccinia virus / immunology
  • Viral Load
  • Viral Vaccines / genetics
  • Viral Vaccines / immunology
  • Viremia / immunology

Substances

  • AIDS Vaccines
  • Adjuvants, Immunologic
  • Antibodies, Viral
  • Immunoglobulin A
  • Immunoglobulin G
  • SAIDS Vaccines
  • Vaccines, DNA
  • Viral Vaccines
  • Granulocyte-Macrophage Colony-Stimulating Factor