Mucosal immune responses in four distinct compartments of women infected with human immunodeficiency virus type 1: a comparison by site and correlation with clinical information.

Because mucosal immune responses may be important in protection against human immunodeficiency virus type 1 (HIV-1), HIV-1-specific immune responses at mucosal sites in natural infection were compared. Total antibody concentrations and HIV-1-specific binding antibody responses in four distinct mucosal sites and serum were assessed in 41 HIV-infected and 19 HIV-seronegative women. HIV-1 gp160-specific IgG responses were detected in >99% of mucosal samples in infected subjects, with the highest titers in genital secretions. HIV-1-specific IgA was detected in the majority of endocervical secretions (94%) and nasal washes (95%) but less often in vaginal washes (51%) and parotid saliva (38%). There was no significant correlation between mucosal immune response and most clinical factors. Based on methodologic considerations, frequencies of detection, and HIV-1-specific responses, nasal washes and genital secretions may each provide important measures of HIV-1-specific mucosal immune responses in infected women.

Characterization of a soluble, oligomeric HIV-1 gp160 protein as a potential immunogen.

We have assessed the oligomeric structure and antigenic properties of an affinity purified gp160 protein (oligo-gp160) using biosensor technology. Sucrose gradient purification analysis identified the existence of tetrameric, dimeric and monomeric forms of the protein. Reactivity to a broad panel of monoclonal antibodies specific for oligomeric gp160, discontinuous epitopes within monomeric gp120 and several linear epitopes within gp120 (V3) and gp41 was demonstrated. International sera from several countries, where HIV-1 clades A-F are prevalent, including type O from Cameroon, were reactive with oligo-gp160 indicating conserved antigenic epitopes. Enhanced immunologic reactivity per gp160 molecule was obtained with oligo-gp160 as compared to other current HIV-1(IIIB) subunit monomeric envelope gp120/gp160 immunogens suggesting higher HIV-1 envelope protein mimicry. HIV-1 antibodies from sera during acute HIV-1 infection were detectable by oligo-gp160 prior to detection with either a recombinant, monomeric gp120 protein or several commercial HIV-1 screening kits suggesting antibodies sensitive to oligomeric gp160 structure may be present earlier in infection. The oligomeric nature of this gp160 protein preparation and high reactivity with divergent mAbs and HIV-1 sera support the use of this protein as an HIV-1 immunogen.