Breadth of Human Immunodeficiency Virus-Specific Neutralizing Activity in Sera: Clustering Analysis and Association with Clinical Variables

Induction of antibodies that neutralize a broad range of human immunodeficiency virus type 1 (HIV-1) isolates is a major goal of vaccine development. To study natural examples of broad neutralization, we analyzed sera from 103 HIV-1-infected subjects. Among progressor patients, 20 % of sera neutralized more than 75 % of a panel of 20 diverse viral isolates. Little activity was observed in sera from long-term nonprogressors (elite controllers). Breadth of neutralization was correlated with viral load, but not with CD4 count, history of past antiretroviral use, age, gender, race/ethnicity, or route of exposure. Clustering analysis of sera by a novel method identified a statistically robust subgrouping of sera that demonstrated broad and potent neutralization activity. Eliciting neutralizing antibodies (NAbs) against human im-munodeficiency virus type 1 (HIV-1) is likely to be crucial for an optimally effective vaccine. To date, the antibodies elicited by vaccines have had weak activity against a limited spectrum of HIV-1 strains (10, 22, 33). However, many HIV-infected patients make NAbs, and a small fraction make extremely potent NAbs with broad cross-reactivity (3, 4, 9, 26, 29, 32)