MONOCLONAL-ANTIBODIES TO P24-CORE PROTEIN OF HIV-1 MEDIATE ADCC AND INHIBIT VIRUS SPREAD IN-VITRO

Background: Certain antigens of the HIV-1, e.g., gp 120-envelop protei ns, can be expressed on the membrane of HIV-infected cells. Little is known about the membrane expression of other HIV-antigens and their in teraction with specific antibodies. Objective: To develop murine monoc lonal antibodies (mAbs) to the p24-core protein of HIV-1 and to charac terise their binding sites and biological activities on HIV-infected T cells. Methods: Monoclonal antibodies were developed from mice hyperi mmunised with a recombinant p24-core protein from HIV-1. Two mAbs were epitope-mapped on overlapping peptides and characterised for their re activity with non-fixed HIV-infected T cells by immunofluorescence sta ining and flow cytometric analysis. Their biological activities were s tudied for antibody-dependent cellular cytotoxicity (ADCC) and suppres sion of viral spread in vitro. Results: The epitopes of two selected m Abs were located on the amino terminal region of p24 in the regions 14 7-152 aa and 178-187 aa, respectively. The antibodies were able to rea ct with living HIV-1 infected cells. The expression of the antigens wa s time-dependent after the infection of certain cell lines by HIV-1. T he mAbs mediated a strong HIV-1-specific ADCC and were able to delay t he spread of HIV-1 for about 6 days in cell cultures. Conclusions: Cer tain epitopes of the p24-core protein of HIV-1 can be expressed on liv ing, HIV-infected T cells and are recognised by specific antibodies. S uch antibodies can destroy infected cells by ADCC or delay the virus s pread, and therefore, should be considered in immunisation strategies against HIV.