Background:   A better understanding of the interactions between HIV-1 positive cells and the cervical epithelium is essential for development of microbicides to prevent sexual transmission of HIV-1 to women.  Our lab has previously demonstrated that cell-associated transmission of HIV-1 by monocytes is the most efficient route of transmission across a model cervical epithelial monolayer and in a hu-PBL-SCID model of vaginal HIV-1 transmission.  In addition, antibody to ICAM-1 has been shown to block transmission of cell-associated HIV-1 in both of these models.  Use of lactobacilli to produce antibody-like single-chain Fvs (scFv) offers many advantages over traditional microbicides, but the available concentration of antibody is limited by the amount of scFv that can be secreted in vivo.  In order to determine whether a significant reduction in the amount of antibody required to block HIV-1 transmission could be achieved, we evaluated the blocking capabilities of antibodies to CD18, the b-chain of the ICAM-1 ligands LFA-1 and Mac-1, both separately and in combination with anti-ICAM-1.

Methods:  Peripheral blood mononuclear cells (PBMC) infected with HIV-1 BaL were added to the apical side of confluent monolayers of HT-3 cervical epithelial cells grown on permeable transwell supports.  After 24 hours, PBMC in the basal compartment were counted, and HIV transmission was measured by p24 ELISA on the basal supernatant.   Data were analyzed using one-way ANOVA with Bonferroni correction by the STATA statistical package.

Results:  Two different anti-CD18 antibodies, H52 and 7E4, were able to reduce transmission of cell-associated HIV-1 by 90±1% and 67±6%, respectively.  Anti-CD18 and anti-ICAM-1 used in 50:50 combination at a total concentration of 5 ug/ml reduced migration of PBMC from HIV-1 infected cultures significantly better (p<0.05) than 20 ug/ml total of either antibody alone.

Conclusions:  These findings indicate that a combination of antibodies to the adhesion receptor pair ICAM-1 and CD18 offers better protection against cell-associated HIV-1 transmission than either antibody alone, and that this combination can protect at a concentration which is feasible for use in a lactobacillus-based microbicide delivery system.