PMID: 1376135Apr 1, 1992Paper

Synergistic neutralization of HIV-1 by human monoclonal antibodies against the V3 loop and the CD4-binding site of gp120

AIDS Research and Human Retroviruses
S A TilleyAbraham Pinter

Abstract

Two distinct regions or epitope clusters of human immunodeficiency virus type 1 (HIV-1) gp120 have been shown to elicit neutralizing antibodies: the V3 loop and the CD4-binding site. We have isolated neutralizing human monoclonal antibodies (HuMAbs) against conserved epitopes in both of these regions. In this study, we demonstrate that an equimolar mixture of two of these HuMAbs, one directed against the V3 loop and the other against the CD4-binding site, neutralizes HIV-1 at much lower concentrations than does either of the individual HuMAbs. Mathematical analysis of this effect suggests cooperative neutralization of HIV-1 by the two HuMAbs and demonstrates a high level of synergy, with combination indices (CIs) of 0.07 and 0.16 for 90% neutralization of the MN and SF-2 strains, respectively. The dose reduction indices (DRIs) for each of the two HuMAbs at 99% neutralization range approximately from 10 to 150. A possible mechanism for this synergism is suggested by binding studies with recombinant gp160 of the MN strain; these show enhanced binding of the anti-CD4 binding site HuMAb in the presence of the anti-V3 loop HuMAb. These results demonstrate the advantage of including both V3 loop and CD4-binding site epitopes in a vac...Continue Reading

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Citations

Sep 1, 1994·Antiviral Research·M S Belen'kii, R F Schinazi
Feb 1, 1996·Immunotechnology : an International Journal of Immunological Engineering·C A DuarteJ Gavilondo
Jun 29, 2002·Current Opinion in Immunology·Flavia Ferrantelli, Ruth M Ruprecht
Oct 1, 1993·AIDS Research and Human Retroviruses·E MurphyF Barré-Sinoussi
Dec 1, 1994·AIDS Research and Human Retroviruses·E M van der DonkR W van der Heijden
Mar 1, 1994·AIDS Research and Human Retroviruses·A Douvas, Y Takehana
Sep 1, 1995·AIDS Research and Human Retroviruses·D N ForthalW E Robinson
Dec 1, 1995·AIDS Research and Human Retroviruses·S Zolla-Pazner, S Sharpe
Nov 28, 2012·AIDS Research and Human Retroviruses·Adi MoseriJacob Anglister
Dec 17, 2008·Journal of Virology·Yasushi AkahoriKimiyasu Shiraki
Jan 1, 1996·Annual Review of Microbiology·G Pantaleo, A S Fauci
Dec 7, 2007·PLoS Medicine·David MontefioriUNKNOWN Working Group convened by the Global HIV Vaccine Enterprise
Nov 18, 2016·Journal of Virology·Seth H PincusEllen S Vitetta

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