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Journal of Virology, May 2009, p. 4102-4111, Vol. 83, No. 9
0022-538X/09/$08.00+0 doi:10.1128/JVI.02173-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
Preclinical Studies of Human Immunodeficiency Virus/AIDS Vaccines: Inverse Correlation between Avidity of Anti-Env Antibodies and Peak Postchallenge Viremia 
,
Jun Zhao ,1,2,
,
Lilin Lai,1,2,
Rama Rao Amara,1,2
David C. Montefiori,3
Francois Villinger,2,4
Lakshmi Chennareddi,1,2
Linda S. Wyatt,5
Bernard Moss,5 and
Harriet L. Robinson1,2*
Emory Vaccine Center, 954 Gatewood Road, Atlanta, Georgia 30329,1 Yerkes National Primate Research Center of Emory University, 954 Gatewood Road, Atlanta, Georgia 30329,2 Department of Surgery, Duke University Medical Center, SORF Building, LaSalle Street Extension, Durham, North Carolina 27710,3 Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia 30322,4 Laboratory of Viral Diseases, National Institutes of Health, National Institute of Allergy and Infectious Diseases, 33 North Drive, Bethesda, Maryland 208925
Received 14 October 2008/ Accepted 7 February 2009
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.
* Corresponding author. Present address: GeoVax, Inc., 1256 Briarcliff Rd. NE, Atlanta, GA 30306. Phone: (404) 727-4397. Fax: (404) 712-9357. E-mail: hrobinson{at}geovax.com
Published ahead of print on 18 February 2009.
Supplemental material for this article may be found at http://jvi.asm.org/.
J.Z. and L.L. contributed equally to this report.
Present address: National Cancer Institute, Vaccine Branch, 41 Medlars Drive, Bethesda, MD 20892.
Journal of Virology, May 2009, p. 4102-4111, Vol. 83, No. 9
0022-538X/09/$08.00+0 doi:10.1128/JVI.02173-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
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