title: 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.
abstract: 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 (IC(50)) 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 IC(50) 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 IC(50) titer and viremia is common to both HIV-1 and HIV-2 infections.
authors.affiliation: Department of Immunology and Infectious Diseases, Harvard School of Public Health, 651 Huntington Avenue, Boston, MA 02115, USA.
authors.forename: Shaun K
authors.initials: SK
authors.lastname: Rodriguez
authors.forename: Abdoulaye Dieng
authors.initials: AD
authors.lastname: Sarr
authors.forename: Adam
authors.initials: A
authors.lastname: MacNeil
authors.forename: Seema
authors.initials: S
authors.lastname: Thakore-Meloni
authors.forename: Aissatou
authors.initials: A
authors.lastname: Gueye-Ndiaye
authors.forename: Ibrahima
authors.initials: I
authors.lastname: Traoré
authors.forename: Mamadou C
authors.initials: MC
authors.lastname: Dia
authors.forename: Souleymane
authors.initials: S
authors.lastname: Mboup
authors.forename: Phyllis J
authors.initials: PJ
authors.lastname: Kanki
mesh_terms: D000328:Adult; D003429:Cross Reactions; D018450:Disease Progression; D005260:Female; D015483:HIV Antibodies / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology* / Q000503:physiopathology / Q000821:virology*; D015497:HIV-1 / Q000276:immunology*; D015498:HIV-2 / Q000276:immunology*; D006801:Humans; D009500:Neutralization Tests; D012675:Senegal; D019562:Viral Load; D014766:Viremia
chemical_list: D015483:HIV Antibodies