A chimeric HIV-1 envelope glycoprotein trimer with an embedded granulocyte-macrophage colony-stimulating factor (GM-CSF) domain induces enhanced antibody and T cell responses

J Biol Chem. 2011 Jun 24;286(25):22250-61. doi: 10.1074/jbc.M111.229625. Epub 2011 Apr 22.


An effective HIV-1 vaccine should ideally induce strong humoral and cellular immune responses that provide sterilizing immunity over a prolonged period. Current HIV-1 vaccines have failed in inducing such immunity. The viral envelope glycoprotein complex (Env) can be targeted by neutralizing antibodies to block infection, but several Env properties limit the ability to induce an antibody response of sufficient quantity and quality. We hypothesized that Env immunogenicity could be improved by embedding an immunostimulatory protein domain within its sequence. A stabilized Env trimer was therefore engineered with the granulocyte-macrophage colony-stimulating factor (GM-CSF) inserted into the V1V2 domain of gp120. Probing with neutralizing antibodies showed that both the Env and GM-CSF components of the chimeric protein were folded correctly. Furthermore, the embedded GM-CSF domain was functional as a cytokine in vitro. Mouse immunization studies demonstrated that chimeric Env(GM-CSF) enhanced Env-specific antibody and T cell responses compared with wild-type Env. Collectively, these results show that targeting and activation of immune cells using engineered cytokine domains within the protein can improve the immunogenicity of Env subunit vaccines.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies, Neutralizing / immunology*
  • Antibody Specificity
  • Granulocyte-Macrophage Colony-Stimulating Factor / genetics*
  • Granulocyte-Macrophage Colony-Stimulating Factor / immunology*
  • HEK293 Cells
  • HIV Envelope Protein gp120 / chemistry
  • HIV Envelope Protein gp120 / genetics*
  • HIV Envelope Protein gp120 / immunology*
  • HIV-1 / immunology
  • Humans
  • Mice
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Engineering
  • Protein Multimerization
  • Protein Structure, Quaternary
  • Protein Structure, Tertiary
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / immunology*
  • T-Lymphocytes, Helper-Inducer / immunology*
  • Viral Vaccines / chemistry
  • Viral Vaccines / genetics
  • Viral Vaccines / immunology


  • Antibodies, Neutralizing
  • HIV Envelope Protein gp120
  • Recombinant Fusion Proteins
  • Viral Vaccines
  • gp120 protein, Human immunodeficiency virus 1
  • Granulocyte-Macrophage Colony-Stimulating Factor