Synergistic neutralization of simian-human immunodeficiency virus SHIV- vpu+ by triple and quadruple combinations of human monoclonal antibodies and high-titer anti-human immunodeficiency virus type 1 immunoglobulins

An Li, Hermann Katinger, Marshall R. Posner, Lisa Cavacini, Susan Zolla-Pazner, Miroslaw K. Gorny, Joseph Sodroski, Ting Chao Chou, Timothy W. Baba, Ruth M. Ruprecht

Research output: Contribution to journalArticlepeer-review

74 Scopus citations

Abstract

We have tested triple and quadruple combinations of human monoclonal antibodies (MAbs), which are directed against various epitopes on human immunodeficiency virus type 1 (HIV-1) envelope glycoproteins, and a high- titer anti-HIV-1 human immunoglobulin (HMG) preparation for their abilities to neutralize a chimeric simian-human immunodeficiency virus (SHIV-vpu+). This virus encodes the HIV. 1 strain IHB env, tat, rev, and vpu genes. The quantitative nature of the Chou-Talalay method (Adv. Enzyme Regul. 22:27-55, 1984) allows ranking of various combinations under identical experimental conditions. Of all triple combinations tested, the most potent neutralization was seen with MAbs 694/98D plus 2F5 plus 2G12 (directed against domains on V3, gp41, and gp120, respectively) as measured by the total MAb concentration required to reach 90% neutralization (90% effective concentration [EC90], 2.0 μ/ml). All triple combinations involving MAbs and/or HMG that were tested yielded synergy with combination index values of < 1; the dose reduction indices (DRIs) ranged from 3.1 to 26.2 at 90% neutralization. When four MAbs (the previous three plus MAb F105, directed against the CD4 binding site) were combined, higher neutralization potency (EC90, 1.8 μml) and a higher degree of synergy compared to any triple combination were seen. The mean DRIs of the quadruple combination were approximately twice that of the most synergistic triple combination. We conclude that human MAbs targeting different HIV-I envelope glycoprotein epitopes exhibit strong synergy when used in combination, a fact that could be exploited clinically for passive immunoprophylaxis against HIV-1.

Original languageEnglish
Pages (from-to)3235-3240
Number of pages6
JournalJournal of Virology
Volume72
Issue number4
DOIs
StatePublished - Apr 1998
Externally publishedYes

Fingerprint

Dive into the research topics of 'Synergistic neutralization of simian-human immunodeficiency virus SHIV- vpu+ by triple and quadruple combinations of human monoclonal antibodies and high-titer anti-human immunodeficiency virus type 1 immunoglobulins'. Together they form a unique fingerprint.

Cite this