Prevention of Infection by a Granulocyte-Macrophage Colony-Stimulating Factor Co-Expressing DNA/modified Vaccinia Ankara Simian Immunodeficiency Virus Vaccine

J Infect Dis. 2011 Jul 1;204(1):164-73. doi: 10.1093/infdis/jir199.

Abstract

A simian immunodeficiency virus (SIV) vaccine coexpressing granulocyte-macrophage colony stimulating factor (GM-CSF) prevented infection in 71% of macaques that received 12 rectal challenges. The SIVsmE660 challenge had the tropism of incident human immunodeficiency virus (HIV) infections and a similar genetic distance from the SIV239 vaccine as intraclade HIV isolates. The heterologous prime-boost vaccine regimen used recombinant DNA for priming and recombinant modified vaccinia Ankara for boosting. Co-expression of GM-CSF in the DNA prime enhanced the avidity of elicited immunoglobulin G for SIV envelope glycoproteins, the titers of neutralizing antibody for easy-to-neutralize SIV isolates, and antibody-dependent cellular cytotoxicity. Impressively, the co-expressed GM-CSF increased vaccine-induced prevention of infection from 25% in the non-GM-CSF co-expressing vaccine group to 71% in the GM-CSF co-expressing vaccine group. The prevention of infection showed a strong correlation with the avidity of the elicited Env-specific antibody for the Env of the SIVsmE660 challenge virus (r = 0.9; P < .0001).

Publication types

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

MeSH terms

  • Animals
  • Antibodies, Neutralizing / blood
  • Antibodies, Viral / blood
  • Cytotoxicity Tests, Immunologic
  • Genetic Vectors
  • Granulocyte-Macrophage Colony-Stimulating Factor / genetics
  • Granulocyte-Macrophage Colony-Stimulating Factor / immunology*
  • Immunization, Secondary / methods
  • Macaca mulatta
  • Male
  • Neutralization Tests
  • SAIDS Vaccines / genetics
  • SAIDS Vaccines / immunology*
  • Simian Acquired Immunodeficiency Syndrome / immunology
  • Simian Acquired Immunodeficiency Syndrome / prevention & control*
  • Simian Immunodeficiency Virus / immunology
  • Simian Immunodeficiency Virus / pathogenicity
  • Vaccination / methods
  • Vaccines, DNA / genetics
  • Vaccines, DNA / immunology*
  • Vaccinia virus / genetics

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • SAIDS Vaccines
  • Vaccines, DNA
  • Granulocyte-Macrophage Colony-Stimulating Factor