Preclinical studies of human immunodeficiency virus/AIDS vaccines: inverse correlation between avidity of anti-Env antibodies and peak postchallenge viremia.

Published

Journal Article

A major challenge for human immunodeficiency virus (HIV)/AIDS vaccines is the elicitation of anti-Env antibodies (Ab) capable of neutralizing the diversity of isolates in the pandemic. Here, we show that high-avidity, but nonneutralizing, Abs can have an inverse correlation with peak postchallenge viremia for a heterologous challenge. Vaccine studies were conducted in rhesus macaques using DNA priming followed by modified vaccinia Ankara boosting with HIV type 1 (HIV-1) immunogens that express virus-like particles displaying CCR5-tropic clade B (strain ADA) or clade C (IN98012) Envs. Rhesus granulocyte-macrophage colony-stimulating factor was used as an adjuvant for enhancing the avidity of anti-Env Ab responses. Challenge was with simian/human immunodeficiency virus (SHIV)-162P3, a CCR5-tropic clade B chimera of SIV and HIV-1. Within the groups receiving the clade B vaccine, a strong inverse correlation was found between the avidity of anti-Env Abs and peak postchallenge viremia. This correlation required the use of native but not gp120 or gp140 forms of Env for avidity assays. The high-avidity Ab elicited by the ADA Env had excellent breadth for the Envs of incident clade B but not clade C isolates, whereas the high-avidity Ab elicited by the IN98012 Env had excellent breadth for incident clade C but not clade B isolates. High-avidity Ab elicited by a SHIV vaccine with a dual-tropic clade B Env (89.6) had limited breadth for incident isolates. Our results suggest that certain Envs can elicit nonneutralizing but high-avidity Ab with broad potential for blunting incident infections of the same clade.

Full Text

Duke Authors

Cited Authors

  • Zhao, J; Lai, L; Amara, RR; Montefiori, DC; Villinger, F; Chennareddi, L; Wyatt, LS; Moss, B; Robinson, HL

Published Date

  • May 2009

Published In

Volume / Issue

  • 83 / 9

Start / End Page

  • 4102 - 4111

PubMed ID

  • 19224993

Pubmed Central ID

  • 19224993

Electronic International Standard Serial Number (EISSN)

  • 1098-5514

Digital Object Identifier (DOI)

  • 10.1128/JVI.02173-08

Language

  • eng

Conference Location

  • United States