Cross-reactive HIV-1-neutralizing activity of serum IgG from a rabbit immunized with gp41 fused to IgG1 Fc: possible role of the prolonged half-life of the immunogen

Vaccine. 2009 Feb 5;27(6):857-63. doi: 10.1016/j.vaccine.2008.11.083. Epub 2008 Dec 10.

Abstract

The elicitation of broadly cross-reactive HIV-1 neutralizing antibodies in humans remains a major challenge in developing a viable AIDS vaccine. We hypothesized that prolonged exposure to candidate vaccine immunogens could enhance the elicitation of such antibodies. In an attempt to develop HIV-1 vaccine immunogens with prolonged half-lives and increased stability, we constructed a fusion protein, gp41Fc, in which a truncated HIV-1 gp41(89.6) was fused to a human IgG(1) Fc. Gp41Fc is stable in solution, retains its antigenic structure and is highly immunogenic in rabbits. The serum titers reached 1:102,400 for the gp41Fc and 1:5,120 for gp140(89.6). Rabbit IgG neutralized diverse HIV-1 isolates and HIV-2, and the neutralization activity was attributed to gp41-specific IgG. The concentration of the gp41Fc in the serum correlated with the neutralization activity of rabbit IgG which recognized mostly conformation-independent epitopes on gp41 and predominantly bound to peptides derived from the gp41 immunodominant loop region. These results suggest that the prolonged half-life of gp41Fc in the serum may enhance the generation of cross-reactive neutralizing antibodies. Further research is needed to confirm and extend these results which may have implications for the development of vaccine immunogens with enhanced capability to elicit cross-reactive HIV-1-neutralizing antibodies.

Publication types

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

MeSH terms

  • AIDS Vaccines / genetics
  • AIDS Vaccines / immunology*
  • AIDS Vaccines / pharmacokinetics*
  • Adjuvants, Immunologic / genetics
  • Adjuvants, Immunologic / pharmacology*
  • Animals
  • Female
  • HIV Antibodies / blood*
  • HIV Envelope Protein gp41 / genetics
  • HIV Envelope Protein gp41 / immunology*
  • HIV-1 / genetics
  • HIV-1 / immunology*
  • HIV-2 / immunology
  • Half-Life
  • Humans
  • Immunoglobulin Fc Fragments / genetics
  • Immunoglobulin Fc Fragments / pharmacology*
  • Neutralization Tests
  • Rabbits
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / immunology
  • Recombinant Fusion Proteins / pharmacokinetics

Substances

  • AIDS Vaccines
  • Adjuvants, Immunologic
  • HIV Antibodies
  • HIV Envelope Protein gp41
  • Immunoglobulin Fc Fragments
  • Recombinant Fusion Proteins
  • gp41 protein, Human immunodeficiency virus 1