Production and characterization of chimeric human papillomavirus l1 virus-like particles for use as a contraceptive vaccine

Abstract

The global unplanned pregnancy rate remains high (nearly 50%) despite decades of workto provide contraception to all who want it. Contraceptive availability is good, but manyunplanned pregnancies are the result of contraceptive failure or deliberate non-use. An anti-sperm contraceptive vaccine seems likely to have a low failure rate and to be attractive tocurrent non-users because of ease of use, and a nonhormonal, prefertilization mechanism ofaction. This thesis details the expression in E. coliand characterization by transmissionelectron microscopy, of a potential anti-sperm vaccine consisting of the self-assembling ma-jor capsid protein of Human Papillomavirus, L1, chimerically decorated with extracellularfragments of the sperm specific calcium channel, CatSper, which is necessary for fertility. L1is well suited to be a scaffold for vaccine design because of the size, structure and stabilityof the particles it spontaneously forms, This is the first use of L1 as a scaffold for the pre-sentation of non-viral antigens, and may help pave the way for a broader adoption of L1 asa standardized scaffold for vaccine design.