BPV VLPs presenting HIV-1 epitopes from membrane-proximal external region of gp41 induced HIV-specific mucosal and systemic cross-clade neutralizing antibodies (P4507)

Abstract

Abstract Two conserved epitopes, located in the membrane-proximal external region (MPER) of gp41 of the human immunodeficiency virus type 1 (HIV-1) envelope spike, are promising targets for vaccine design in efforts to elicit 2F5 and 4E10-like anti-HIV-1 broadly neutralizing antibodies. Since most HIV-1 infections initiate at mucosal surfaces, the induction of mucosal neutralizing antibodies is necessary and of utmost importance to counteract HIV-1 infection. Here, we utilized a mucosal vaccine vector, bovine papillomavirus (BPV) virus-like particles (VLPs), as a platform to present HIV-1 neutralizing epitopes by inserting the extended 2F5 (ELLELDKWASLWN) or 4E10 epitope (NWFDITNWLWYIK) or the MPER domain into surface loops of BPV L1 respectively. In order to enhance the presentation of the neutralizing epitopes, the modified 4E10 and 2F5 epitope were presented by inserting two alanines (AA) in N-terminal, C-terminal or both terminals of the epitopes. The chimeric VLPs presenting MPER domain resembled the HIV-1 natural epitopes better than the chimeric VLPs presenting unmodified single ones. Moreover, N-terminal modified 2F5 epitope further enhanced the epitope presentation when inserted in D-E loop. Oral immunization of mice with the chimeric VLPs displaying 2F5 or MPER elicited epitope-specific serum IgGs and mucosal secretory IgAs. The antibodies induced by chimeric VLPs presenting MPER domain are capable of neutralizing clade B and clade C HIV-1 viruses, although modest.