Autoantibodies induced by chimeric cytokine-HIV envelope glycoprotein immunogens. Academic Article uri icon

Overview

MeSH

  • Animals
  • Cell Line, Tumor
  • Humans
  • Mice
  • Protein Structure, Secondary
  • Rabbits

MeSH Major

  • Autoantibodies
  • Autoimmune Diseases
  • HIV-1
  • Interleukins
  • Recombinant Fusion Proteins
  • env Gene Products, Human Immunodeficiency Virus

abstract

  • Cytokines are often used as adjuvants to increase the immunogenicity of vaccines because they can improve the immune response and/or direct it into a desired direction. As an alternative to codelivering Ags and cytokines separately, they can be fused into a composite protein, with the advantage that both moieties act on the same immune cells. The HIV-1 envelope glycoprotein (Env) spike, located on the outside of virus particles and the only relevant protein for the induction of neutralizing Abs, is poorly immunogenic. The induction of anti-Env Abs can be improved by coupling Env proteins to costimulatory molecules such as a proliferation inducing ligand (APRIL). In this study, we evaluated the immunogenicity of chimeric molecules containing uncleaved Env gp140 fused to the species-matched cytokines IL-21 or GM-CSF in rabbits and mice. Each cytokine was either fused to the C terminus of Env or embedded within Env at the position of the variable loops 1 and 2. The cytokine components of the chimeric Env-GM-CSF and Env-IL-21 molecules were functional in vitro, but none of the Env-cytokine fusion proteins resulted in improved Ab responses in vivo. Both the Env-GM-CSF and the Env-IL-21 molecules induced strong anticytokine Ab responses in both test species. These autoimmune responses were independent of the location of the cytokine in the chimeric Env molecules in that they were induced by cytokines inserted within the variable loops 1 and 2 of Env or fused to its C terminus. The induction of undesired autoimmune responses should be considered when using cytokines as costimulatory molecules in fusion proteins.

publication date

  • May 15, 2014

has subject area

  • Animals
  • Autoantibodies
  • Autoimmune Diseases
  • Cell Line, Tumor
  • HIV-1
  • Humans
  • Interleukins
  • Mice
  • Protein Structure, Secondary
  • Rabbits
  • Recombinant Fusion Proteins
  • env Gene Products, Human Immunodeficiency Virus

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC4018769

Digital Object Identifier (DOI)

  • 10.4049/jimmunol.1303401

PubMed ID

  • 24729614

Additional Document Info

start page

  • 4628

end page

  • 4635

volume

  • 192

number

  • 10