Short communication: Anti-HIV-1 envelope immunoglobulin Gs in blood and cervicovaginal samples of Beninese commercial sex workers

Abstract

Characterization of the immune correlates of protection against HIV infection is crucial for the development of preventive strategies. This study examined HIV-1 envelope (Env) glycoproteins, specifically immunoglobulin G (IgG), in systemic and mucosal compartments of female Beninese commercial sex workers (CSWs). Samples of 23 HIV-1-positive and 20 highly exposed HIV-1-seronegative (HESN) CSWs were studied. HIV-1 Env-specific IgG detection in sera and cervicovaginal lavages (CVLs) from the study population was done by cell-based ELISA. The HIV neutralizing activity was evaluated with a neutralization assay. The HIV-1-specific antibody-dependent cellular cytotoxicity (ADCC) response of the cohort was measured with a FACS-based assay evaluating the ADCC-mediated elimination of gp120-coated target cells. No anti-HIV-1 Env-specific IgG neutralizing or ADCC activities were detected in samples from HESN CSWs. Samples from HIV-1-infected CSWs presented ADCC activity in both sera and CVLs. Anti-Env IgG from sera and CVLs from HIV-1-infected CSWs preferentially recognized Env in its CD4-bound conformation. HIV-1-infected CSWs have ADCC-mediating IgG that preferentially recognizes Env in its CD4-bound conformation at the mucosal site.

FIG. 1.

Anti-immunoglobulin G (IgG) envelope HIV-1-specific antibody detection, neutralization, and antibody-dependent cellular cytotoxicity (ADCC) by sera and cervicovaginal lavages (CVLs) from the study population. In both sera and CVLs of HIV-1-positive commercial sex workers (CSWs), we observed that coexpression of cellular CD4 increased the detection of IgGs. Sera (A) and CVLs (B) from the cohort described in Table 1 were screened by a cell-based ELISA assay for the presence of IgG directed against Env in the absence or presence of coexpressed cellular CD4 receptor. The detection of IgG for each patient was calculated taking the relative luminescence unit (RLU) value for each condition subtracted by the RLU for murine leukemia virus (MLV) of each individual. The paired t-test (**p<0.01, ***p<0.001, ****p<0.0001) was used to assess the significance between groups. Sera from HIV-1-positive CSWs but not from HIV-1-negative CSWs neutralized HIV-1. Increasing serum and CVL dilutions from HIV-1-positive CSWs (C, D) or HIV-1-negative CSWs (E, F) were incubated for 1 h at 37°C with HIV-1 viral particles bearing the primary clade B (HIV-1_YU2) envelope before infection. Sera sample from every individual was also screened with MLV to test the specificity of the reduction of infectivity (not shown). The Wilcoxon matched-pairs test (*p<0.05, **p<0.01, ***p<0.001) was used to assess the significance between the different conditions. Sera and CVLs of some HIV-1-positive CSWs were able to mediate elimination of gp120-coated target cells by ADCC. HIV-1-positive CSWs and HIV-1-negative CSWs were screened by serum-mediated (G) and CVL-mediated (H) gp120-coated target CEM-NK cells. ADCC killing was measured using peripheral blood mononuclear cells (PBMCs) from healthy donors as effector cells. The Mann–Whitney test was used to assess statistical significance (*p<0.05, **p<0.01, ***p<0.001).