Dustin Mullaney,

Sponsor or Client: 

Title:

Generating a Novel, Adjuvanted HPV Vaccine Platform Using Click Chemistry: A proof of concept study

Abstract:

Human papillomavirus (HPV) is the primary cause of cervical cancer. Despite the availability of an HPV vaccine, Native Americans are disproportionately affected by HPV and cervical cancer. This is attributable to the fact that the current HPV vaccine does not cover several high risk (cancer causing) types of HPV (hrHPV). The current vaccine is based on virus-like-particles (VLPs) generated from the spontaneous self-assembly of the HPV L1 coat protein, but a vaccine built around the L2 coat protein, which does not spontaneously self-assemble into VLPs, would provide better coverage against hrHPVs that are prevalent in the Native American community. In addition, an adjuvanted HPV vaccine could be more immunogenic and not require two doses as does the current vaccine. The aim of this project is to generate an adjuvanted HPV vaccine using a genetically engineered MS2 VLP which displays the L2 antigen. The experiments presented here evaluated the feasibility of using a click chemistry reagent provided by collaborators at the University of Arizona to conjugate an adjuvant to this VLP platform. This click reagent does not require a copper catalyst, improving the feasibility of using click chemistry under biological conditions. We developed a conjugation protocol which uses this reagent, and report the successful conjugation of a PEG-Azide to an MS2 VLP derivative. In the future this protocol will be used to conjugate CpG DNA adjuvants to genetically engineered VLPs which display the L2 antigen.