>> Immunogenic Display of Cross-Neutralizing L2 Peptides on bacteriophage Virus-like Particles
14:00 PM - 14:15 PM
1Department of Molecular Genetics and Microbiology, University of New Mexico, Albuquerque, NM, USA; 2Laboratory of Cellular Oncology, National Cancer Institute, Bethesda, MD, USA.
The immunogenicity of an antigen can be dramatically increased by displaying it in a dense, multivalent context, such as on the surface of a virus or virus-like particle (VLP). We have developed highly versatile platforms for display of target antigens based on VLPs of several related RNA bacteriophage. These platforms can be used to generate recombinant VLPs, in which target peptides are genetically inserted into surface-exposed loops on VLPs. Alternatively, we can conjugate synthetic peptides to the surface of VLPs using chemical crosslinkers. We have used both approaches to develop vaccines against a broadly cross-neutralizing epitope found in the HPV minor capsid protein L2. Both recombinant bacteriophage PP7 VLPs displaying an HPV16 L2 epitope (representing amino acids 17-31) and bacteriophage Qß VLPs conjugated with a synthetic cyclic HPV16 L2 peptide (representing amino acids 14-40) induced high titer L2-peptide specific IgG antibody responses in mice. The flexible nature of our conjugation approaches has allowed us to generate hybrid particles, in which multiple peptides derived from different HPV types are displayed on a single VLP. The immunogenicity of these hybrid particles will also be presented. We tested the efficacy of one of our vaccines in an in vivo genital challenge model. PP7 VLPs displaying the HPV16 L2 epitope generated robust anti-HPV16 L2 antibodies that protected mice (>98% reduction in luciferase signal) from high-dose (10^8 IU) genital challenge with HPV16 pseudovirus. In addition, vaccination protected mice (84% protection) from pseudoinfection with a similar dose of a heterologous HPV type, HPV45. Thus, VLP-display of cross-neutralizing HPV L2 epitopes is an effective approach for inducing high titer neutralizing antibodies.