title: Preclinical studies of human immunodeficiency virus/AIDS vaccines: inverse correlation between avidity of anti-Env antibodies and peak postchallenge viremia.
abstract: 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.
authors.affiliation: Emory Vaccine Center, Atlanta, Georgia 30329, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhao
authors.forename: Lilin
authors.initials: L
authors.lastname: Lai
authors.forename: Rama Rao
authors.initials: RR
authors.lastname: Amara
authors.forename: David C
authors.initials: DC
authors.lastname: Montefiori
authors.forename: Francois
authors.initials: F
authors.lastname: Villinger
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Chennareddi
authors.forename: Linda S
authors.initials: LS
authors.lastname: Wyatt
authors.forename: Bernard
authors.initials: B
authors.lastname: Moss
authors.forename: Harriet L
authors.initials: HL
authors.lastname: Robinson
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000818:Animals; D004353:Drug Evaluation, Preclinical; D015686:Gene Products, env / Q000276:immunology*; D015683:Gene Products, gag / Q000276:immunology; D015483:HIV Antibodies / Q000276:immunology* / Q000494:pharmacology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008253:Macaca mulatta; D008297:Male; D015302:Simian Immunodeficiency Virus / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D017186:Titrimetry; D014766:Viremia / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D015686:Gene Products, env; D015683:Gene Products, gag; D015483:HIV Antibodies