Dichotomy in Cross-Clade Reactivity and Neutralization by HIV-1 Sera: Implications for Active and Passive Immunotherapy

Authors

• Lisa A. Cavacini, Harvard Medical SchoolFollow
• Mark Duval, Beth Israel Deaconess Medical Center
• Ajay Patil, Beth Israel Deaconess Medical Center
• Charles Wood, University of Nebraska-LincolnFollow
• Kanneth H. Mayer, Brown University
• Ruth M. Ruprecht, Harvard Medical School
• Marshall L. Posner, Harvard Medical School

Document Type

Article

Date of this Version

2005

Comments

Published in the Journal of Medical Virology 76: 146–152 (2005). DOI: 10.1002/jmv.20339. Copyright 2005, Wiley-Liss. Used by permission.

Abstract

The identification of broadly reactive and cross-clade neutralizing antibodies will facilitate the development of a more universally effective vaccine for human immunodeficiency virus (HIV). Antibodies in sera from individuals infected with Clade B HIV bind native primary viral isolates, and virus binding correlates with neutralization and stable clinical disease. In this study, we quantified cross-clade antibody reactivity and neutralization by Clades B and C sera. Primary viral isolates were captured by serum IgG bound to anti-human IgG and quantitated as p24 released by lysis of captured virus. Neutralization was determined using PHA-stimulated PBMC. Clade B antibodies reacted more frequently with Clade B R5 virus, but positive sera captured quantitatively more X4 virus than R5 and R5X4 virus. Clade B sera reacted less frequently and captured less Clade C virus than Clade B virus. Antibodies in Clade C sera captured Clades B and C isolates with equal frequency and quantity. There was no difference in neutralization of Clade B virus by either group of sera; however, Clade C sera neutralized Clade C virus, whereas Clade B sera were ineffective against Clade C virus. Thus, there are distinct differences in cross-clade reactivity of and neutralization by antibodies induced in response to Clade C infection compared to Clade B infection. Understanding antibody responses to native virions after Clade C infection and cross clade antibody behavior has implications for understanding pathogenesis and vaccine development.