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141 Characteristics of the Earliest Cross-Neutralizing Antibody Response to HIV-1

Mikell, Iliyana1,2; Sather, D Noah1; Kalams, Spyros3; Altfeld, Marcus4; Alter, Galit4; Stamatatos, Leonidas1,2*

JAIDS Journal of Acquired Immune Deficiency Syndromes: April 2011 - Volume 56 - Issue - p 57
doi: 10.1097/01.qai.0000397327.26622.5c

1Seattle BioMed, Seattle, Washington; 2Department of Global Health, University of Washington, Seattle, Washington; 3Division of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN; and 4Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Boston, MA

Recent cross-sectional analyses of HIV-1+ plasmas indicated that broadly cross-reactive neutralizing antibody responses are developed by 10% - 30% of anti-retroviral naïve HIV-1+ subjects. The timing of the development of such anti-viral responses is unknown. It is also unknown whether the emergence of these responses coincides with the appearance of antibody specificities to a single or multiple regions of the viral envelope glycoprotein (Env). Here we report that anti-HIV-1 cross-neutralizing antibody responses first become evident, on average, at 2.5 years, and as early as 1 year, following infection. Broad cross-neutralizing antibody responses do not appear to develop later in infection. Although plasma neutralizing antibody responses of narrow breadth, target epitopes on the monomeric gp120 Env subunit that are located outside the conserved CD4-binding site (CD4-BS), the earliest cross-neutralizing antibody responses primarily target epitopes that are located within the CD4-BS or epitopes that are not present on monomeric gp120 but present on virion-associated trimeric form of Env. The relative contribution of these two epitope specificities to the plasma's overall cross-neutralizing activities is patient-depended. Once cross-neutralizing antibody responses emerge, they do not wane for extended periods of time and their epitope-specificities remain unchanged.

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