Multiple aligned sequence editor (MASE). complexes differed between acute and chronic contamination (anti-gp41 Ab in acute contamination and anti-gp120 in chronic contamination), potentially suggesting different functions in immunopathogenesis for complexes arising at different stages of contamination. We also decided the ability of circulating IgG from AHI to bind infectious versus noninfectious virions. Similar to a nonneutralizing anti-gp41 monoclonal antibody (MAb), purified plasma IgG from acute HIV-1 subjects bound both infectious and noninfectious virions. This was in contrast to the neutralizing antibody 2G12 MAb that bound predominantly infectious virions. Moreover, the initial antibody response captured acute HIV-1 virions without selection for different HIV-1 envelope sequences. In total, this study demonstrates that this composition of immune complexes are dynamic over the course of HIV-1 contamination and are comprised initially of antibodies that nonselectively opsonize both infectious and noninfectious virions, likely contributing to the lack of efficacy of the antibody response during acute contamination. INTRODUCTION The major challenge to development of a successful human immunodeficiency computer virus type 1 (HIV-1) preventive vaccine is an incomplete understanding of the correlates of protective immunity to HIV-1 contamination. A clear understanding of the early events following HIV-1 transmission, especially HOE 32020 the short time windows from transmission to the establishment of the latent pool of HIV-1-infected CD4+ T cells, is critical to the design of a protective vaccine (reviewed in reference 26). Details of the earliest host-pathogen interactions can provide insights into the challenges that the initial immune response may face during transmission and establishment of contamination. We have previously reported that HOE 32020 this first detectable B-cell response to HIV-1 in acute HIV-1 contamination (AHI) is in the form of immunoglobulin (Ig)CHIV-1 virion immune complexes (ICs) approximately 8 days after the time of the first detectable plasma viral load ((13), and FcR alleles were associated with protection in a Vax004 vaccine trial (12), suggesting that Fc receptor-mediated activities do contribute to control of HIV-1. Opsonization of virions by complement may also be an important component of viral pathogenesis since CD21 on B cells can bind complement-coated virions and propagate contamination of T cells (27), although HIV-1 virions also incorporate host complement inhibitor molecules during virion budding HOE 32020 (37). Others have also found that antibody-opsonized HIV-1 without the presence of complement components could enhance HIV-1 contamination (2, 3, 18). The initial induced HIV-1-specific antibodies do not exhibit traditional neutralizing activity, do not mediate antibody-dependent cellular viral inhibition (ADCVI), do not drive HIV-1 Env escape mutations, and do not impact initial viral load dynamics (42). Thus, a critical question is whether the initial gp41 Env IgG response captures infectious virions, and if so, are a sufficient proportion of virions coated with Env antibody in AHI to potentially mediate an antiviral effect? To address these questions, we have quantified plasma IgG-virion ICs, decided the proportion of virions bound to IgG during AHI, decided the kinetics of the production of acute ICs, and decided the ability of acute HIV-1-purified IgG from AHI to bind infectious virions luciferase (LucR) reporter viruses (designated NL-LucR.T2A-Env.ecto) (9) expressing envelope regions from lab-adapted NL4-3 or transmitted/founder viruses (CH040 and WITO) (19) were generated as described previously (9, 14). Briefly, proviral DNA was transfected into 293T cells by Fugene HD HEY2 (Roche). Working stocks were amplified by passaging computer virus in human peripheral blood mononuclear cells (PBMCs) (American Red Cross). Computer virus supernatants were collected every 2 or 3 days and filtered through a 0.45-m syringe HOE 32020 filter, and titers were determined on TZM-bl cells (obtained through the NIH AIDS Research and Reference Reagent Program, Division of AIDS, NIAID, NIH, from John C. Kappes, Xiaoyun Wu, and Tranzyme, Inc.). Wild-type HIV-1 MN was amplified by the H9 cell line (obtained from the NIH AIDS Research and Reference Reagent Program, Division of AIDS, NIAID, NIH, from Robert Gallo). HIV-1-specific binding antibody assay. Plasma HIV-1-specific antibodies were measured by a custom HIV-1 binding antibody multiplex assay as previously described (44). HIV-specific Ab isotypes were detected with mouse-anti human IgG (Southern Biotech, Birmingham, AL), conjugated to phycoerythrin, at 4 g/ml. Antibody measurements are acquired on a Bio-Plex instrument (Bio-Rad, Hercules, CA), and the readout is in mean fluorescent intensity (MFI) or g/ml equivalents based on a 2F5.