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Journal of Virology, May 2007, p. 5331-5338, Vol. 81, No. 10
0022-538X/07/$08.00+0     doi:10.1128/JVI.02789-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Comparison of Heterologous Neutralizing Antibody Responses of Human Immunodeficiency Virus Type 1 (HIV-1)- and HIV-2-Infected Senegalese Patients: Distinct Patterns of Breadth and Magnitude Distinguish HIV-1 and HIV-2 Infections{triangledown}

Shaun K. Rodriguez,1 Abdoulaye Dieng Sarr,1 Adam MacNeil,1 Seema Thakore-Meloni,1 Aissatou Gueye-Ndiaye,2 Ibrahima Traoré,2 Mamadou C. Dia,2 Souleymane Mboup,2 and Phyllis J. Kanki1*

Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts,1 Laboratory of Bacteriology and Virology, Cheikh Anta Diop University, Dakar, Senegal2

Received 18 December 2006/ Accepted 6 February 2007

Neutralizing antibody responses against heterologous isolates in human immunodeficiency virus type 1 (HIV-1) and HIV-2 infections were compared, and their relationships with established clinical markers of progression were examined. Neutralizing responses against 7 heterologous primary isolates and 1 laboratory strain were compared between 32 untreated HIV-1-infected subjects and 35 untreated HIV-2-infected subjects using a pseudotyped reporter virus assay. The breadth of the neutralizing response, defined as the proportion of panel viruses positively neutralized by patient plasma, was significantly greater among HIV-2-infected subjects than among HIV-1-infected subjects. Notably, for fully one-third of HIV-2 subjects, all viruses were effectively neutralized in our panel. Magnitudes of responses, defined as reciprocal 50% inhibitory concentration (IC50) titers for positive reactions, were significantly greater among HIV-1-infected subjects than among HIV-2-infected subjects. When plasma samples from HIV-1 patients were tested for cross-neutralization of HIV-2 and vice versa, we found that these intertype responses are very rare and their prevalences comparable in both HIV-1 and HIV-2 infection. The significantly higher magnitude of heterologous responses for HIV-1 compared to HIV-2 prompted us to examine associations with viremia, which is known to be significantly higher in HIV-1 infection. Importantly, there was a significant positive correlation between the IC50 titer and viral load within both the HIV-1 and HIV-2 groups, suggesting heterologous antibodies may be driven by viral replication. We conclude that HIV-2 infection is characterized by a broad, low-magnitude intratype neutralization response, while HIV-1 is characterized by a narrower but higher-magnitude intratype response and that a significant positive association between the IC50 titer and viremia is common to both HIV-1 and HIV-2 infections.

* Corresponding author. Mailing address: Department of Immunology and Infectious Diseases, Harvard School of Public Health, 651 Huntington Avenue, Boston, MA 02115. Phone: (617) 432-1267. Fax: (617) 432-3575. E-mail: pkanki{at}hsph.harvard.edu

{triangledown} Published ahead of print on 14 February 2007.

Journal of Virology, May 2007, p. 5331-5338, Vol. 81, No. 10
0022-538X/07/$08.00+0     doi:10.1128/JVI.02789-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.





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