IGF::OT::IGF SUPPORT FOR HPV16L1/RG1 CHIMERIC VIRUS-LIKE PARTICLE VACCINE CLINICAL DEVELOPMENT TASKS 1&2 PP: 9/25/2015 TO 9/24/2018

University Of Illinois At Urbana-Champaign, Urbana IL

Investigators

Abstract

Background: Currently marketed HPV vaccines protect against infection by virus types associated with up to 90% of cervical/mucosal cancers (Guardasil 9). To potentially expand protection to all HPV types, Drs. Richard Roden, of Johns Hopkins University, and Reinhard Kirnbauer, of the Medical University of Vienna, have designed a chimeric HP16 L1 virus like particle that displays a highly conserved, immunogenic epitope of L2 on the surface of the VLP. Preclinical studies support the effectiveness of this vaccine against a large number of HPV types. The NCI PREVENT Cancer Preclinical Drug Development Program is currently producing clinical grade HPV16L1/RG1 chimeric VLP vaccine for Phase I and Phase II, proof of concept testing. The product will be adjuvanted with alum/MPL and thus very similar to Cervarix. While the details of the clinical testing plan are still under development, it is anticipated that the Phase I testing will involve three vaccinations (at 0, 2 and 6 months) with dose-escalation through three dose-levels (20, 40, and 80 µg). The primary objective will be to establish safety of the vaccine. The secondary objective will be to demonstrate immunogenicity (generation of neutralizing antibodies to HPV16L1 VLP and L1/L2 VLP from at least one HPV type not represented in the currently marketed vaccines). Immunogenicity will be determined from in vitro serum neutralization assays and protection (by passive transfer) of mice from vaginal challenge with pseudotyped reporter VLP. Phase II testing will be directed towards definitive studies of the spectrum of HPV protection.