Display of conserved Human Immunodeficiency Virus Type 1 gp41 membrane-proximal external region epitopes on bovine papilloma virus-like particles (53.19)

Abstract

Abstract Human immunodeficiency virus type 1 (HIV-1) is mainly transmitted via mucosa; an effective vaccine must induce appropriate mucosal immunity to contain virus transmission. To induce 2F5/4E10-like broadly neutralizing antibody at mucosa sites, the HIV-1 epitopes ELLELDKWASLWN and NWFDITNWLWYIK, recognized by broadly neutralizing antibodies 2F5 and 4E10, respectively, and a short membrane-proximal external region (MPER) (LELDKWASLWNWFDITNW) of HIV gp41 (containing both epitopes) were displayed on three surface loops of bovine papillomavirus (BPV) 1 L1 protein. BPV L1 can form virus-like particles which are mucosa-tropic. Chimeric virus-like particles (CVLPs) were assembled when the fusion proteins were expressed in sf9 cells. CVLPs had sizes similar to those of BPV particles and could be recognized by HIV broadly neutralizing antibodies 2F5 and 4E10. By competition ELISA, CVLP showed strong abilities for competitively binding to 2F5 in the presence of competitors, the peptide ELLELDKWASLWN or to 4E10 in the presence of peptide NWFDITNWLWYIK. Epitope-specific serum IgG and intestinal secretory IgA responses were elicited after oral immunization of mice with the CVLPs. The antibodies specifically recognized HIV-1 gp160 envelope glycoprotein expressed on the cell surface. These findings provide valuable information for an HIV vaccine immunogen design to induce 2F5/4E10-like broadly neutralizing antibody via presenting HIV-1 gp41MPER epitope on BPV VLPs.