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Session 90 Poster Abstracts
HIV-1 Neutralizing Antibodies
Wednesday, 1:30 - 3:30 pm
Hall D


500    
Neutralization and Infectivity Characteristics of Envelope Glycoproteins from Human Immunodeficiency Virus Type 1- infected Donors Whose Sera Exhibit Broadly Cross-reactive Neutralizing Activity
Fatim Cham*1, P Zhang1, L Heyndrickx2, P Bouma1, M Zwick3, D Burton3, H Katinger4, J Robinson5, S Zolla-Pazner6, G van der Groen7, and G Quinnan8
1Uniformed Svcs Univ of the Hlth Sci, Bethesda, MD, USA; 2Inst of Tropical Med, Anwerp, Belgium; 3The Scripps Clin and Res Fndn, La Jolla, CA, USA; 4Inst of Applied Microbiology, Univ of Life Sci, Vienna, Ausria; 5Tulane Univ, New Orleans, LA, USA; 6New York Veterans Admin Med Ctr, NY, USA; 7Inst of Tropical Med, Anwerp, Belgium; and 8Uniformed Svcs Univ of the Hlth Sci, Bethesda, MD, USA

Background:  An HIV-1 vaccine capable of inducing broadly cross-reactive neutralizing (BCN) antibodies is a long-sought goal.

Methods:  In the present study, we characterized HIV-1 envelop (Env) glycoprotein of HIV-1 strains from 6 donors with BCN antibodies and control, non-BCN donors. The new BCN Env differed from a previously obtained BCN Env, designated R2, in being neither CD4-independent, nor sensitive to neutralization by monoclonal antibodies against CD4-induced epitopes. However, 5 of the 6 new BCN Env were highly sensitive to neutralization by the monoclonal antibodies 2F5 and 4E10. Env were obtained from 2 BCN donors, 1400 and 2400, at time points 6 months apart.

Results:  Late Env clones from each of these donors were comparatively resistant to 2F5 neutralization and had 2F5 epitope mutations that caused resistance to neutralization by 2F5, in 1 case, by 4E10. The converse mutation of the 1400 clone had the reverse effect on 2 non-BCN Env. Quasi-species analyses demonstrated emergence of the 2F5-resistant genotype in donor 2400. This is the first example reported of an apparent neutralization escape mutation at the 2F5 epitope occurring in vivo. A662T, the mutation in clone 1400, has been reported to the HIV database in only 1 other sequence.

Concluisions:  We suggest that the BCN antibodies in the sera of these 2 donors may have resulted from infection with HIV-1 strains that displayed Env that were particularly immunogenic with respect to induction of antibodies against neutralization epitopes in the membrane proximal region of gp41, and these Env may be useful vaccine components. The BCN antibodies in the sera of these 2 donors may have resulted from infection with HIV-1 strains that displayed Env that were particularly immunogenic with respect to induction of antibodies against neutralization epitopes in the membrane proximal region gp41. These Env may be useful vaccine components.

Keywords: HIV-1 Envelope glycoprotein; Neutralization; Monoclonal antibodies