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Journal of Virology, June 2006, p. 5211-5218, Vol. 80, No. 11
0022-538X/06/$08.00+0     doi:10.1128/JVI.00201-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Evidence for Potent Autologous Neutralizing Antibody Titers and Compact Envelopes in Early Infection with Subtype C Human Immunodeficiency Virus Type 1

Bing Li,1,2,{dagger} Julie M. Decker,6,7,8,{dagger} Roy W. Johnson,1,2 Frederic Bibollet-Ruche,6,7,8 Xiping Wei,6,7,8 Joseph Mulenga,9 Susan Allen,3 Eric Hunter,1,2,4 Beatrice H. Hahn,7,8 George M. Shaw,6,7,8 Jerry L. Blackwell,1,4,5 and Cynthia A. Derdeyn1,2,4*

Yerkes National Primate Research Center,1 Department of Pathology and Laboratory Medicine,2 Department of Global Health, Rollins School of Public Health,3 Emory Vaccine Center,4 Division of Infectious Diseases, Emory University, Atlanta, Georgia 30329,5 Howard Hughes Medical Institute,6 Department of Medicine,7 Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama 35294,8 Zambia Blood Transfusion Service, Lusaka, Zambia9

Received 27 January 2006/ Accepted 14 March 2006

Information about neutralizing antibody responses in subtype C-infected individuals is limited, even though this viral subtype causes the majority of AIDS cases worldwide. Here we compared the course and magnitude of the autologous neutralizing antibody (NAb) response against viral envelope (Env) glycoproteins present during acute and early infection with subtypes B and C human immunodeficiency virus type 1 (HIV-1). NAb responses were evaluated in 6 subtype B-infected and 11 subtype C-infected subjects over a mean evaluation period of 25 months using a pseudovirus reporter gene assay. All subjects in the C cohort were infected through heterosexual contact, while five of the six subjects in the B cohort were infected via male-to-male contact. The kinetics and magnitude of the NAb responses varied among subjects in the B and C cohorts; however, the median 50% inhibitory concentration (IC50 titer) reached by antibody in the plasma of subtype C-infected subjects, overall, was 3.5-fold higher than in the subtype B-infected subjects (P = 0.06). The higher titers of NAbs in the C cohort were associated with viruses having significantly shorter amino acid length (P = 0.002) in the V1 to V4 region of the surface Env glycoprotein, gp120, compared to the B cohort. Despite the potency of the autologous subtype C NAb response, it was not directed against cross-neutralizing epitopes. These data demonstrate that subtype C Envs elicit a potent yet restricted NAb response early in infection that frequently reaches IC50 titers in excess of 1:1,000 and suggest that clade-specific differences may exist in Env immunogenicity or susceptibility to neutralization.

* Corresponding author. Mailing address: Emory Vaccine Center, Emory University, 954 Gatewood Rd., Suite 1024, Atlanta, GA 30329. Phone: (404) 727-8594. Fax: (404) 727-9316. E-mail: cynthia.derdeyn{at}emory.edu.

{dagger} B.L. and J.M.D. contributed equally to this work.

Journal of Virology, June 2006, p. 5211-5218, Vol. 80, No. 11
0022-538X/06/$08.00+0     doi:10.1128/JVI.00201-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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