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  • Oral presentation
  • Open Access

Natural and engineered antibodies against HIV

  • 1
Retrovirology20063 (Suppl 1) :S100

https://doi.org/10.1186/1742-4690-3-S1-S100

  • Published:

Keywords

  • Infected Person
  • Primary Isolate
  • Potent Neutralize
  • Bifunctional Protein
  • Coreceptor Binding

The humoral arm of the immune system exerts continual selective pressure on HIV replication in the infected person. We have described a conserved epitope within the gp120 V3 loop that is masked in the native Env trimer on CCR5-restricted (R5) HIV-1 virions, but fully exposed on CXCR4-using (X4, R5X4) virions. The ability of a monoclonal antibody against this epitope to selectively neutralize CXCR4-using but not CCR5-restricted primary isolates raises the question of whether in vivo neutralizing antibody selection pressure in the acutely infected person plays a major role in the selective transmission of R5 viruses.

We are exploiting antibodies to engineer novel bifunctional proteins against HIV infection. One agent, designated sCD4-17b, is based on the sequential receptor binding mechanism of gp120: first to CD4, then to coreceptor. The sCD4 moiety of the chimeric protein binds and induces the conformational change required to expose/create the highly conserved "bridging sheet" involved in coreceptor binding and containing the 17b epitope. The potent neutralizing activity of sCD4-17b against diverse HIV-1 primary isolates suggests its potential utility as a topical microbicide to protect against HIV-1 sexual transmission. [1, 2].

Authors’ Affiliations

(1)
Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA

References

  1. Lusso P, Earl PL, Sironi F, Santoro F, Ripamonti C, Scarlatti G, Longhi R, Berger EA, Burastero SE: Cryptic nature of a conserved, CD4-inducible V3 loop neutralization epitope in the native envelope glycoprotein oligomer of CCR5-restricted, but not CXCR4-using, primary human immunodeficiency virus type 1 strains. J Virol. 2005, 79: 6957-6968. 10.1128/JVI.79.11.6957-6968.2005.PubMed CentralView ArticlePubMedGoogle Scholar
  2. Dey B, Del Castillo CS, Berger EA: Neutralization of human immunodeficiency virus type 1 by sCD4-17b, a single-chain chimeric protein, based on sequential interaction of gp120 with CD4 and coreceptor. J Virol. 2003, 77: 2859-2865. 10.1128/JVI.77.5.2859-2865.2003.PubMed CentralView ArticlePubMedGoogle Scholar

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