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Dichotomy in cross-clade reactivity and neutralization by HIV-1 sera: Implications for active and passive immunotherapy

✍ Scribed by Lisa A. Cavacini; Mark Duval; Ajay Patil; Charles Wood; Kenneth H. Mayer; Ruth M. Ruprecht; Marshall R. Posner


Publisher
John Wiley and Sons
Year
2005
Tongue
English
Weight
156 KB
Volume
76
Category
Article
ISSN
0146-6615

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✦ Synopsis


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. J. Med. Virol. 76:146–152, 2005. © 2005 Wiley‐Liss, Inc.