Project 2 - VLP-based vaccines displaying PorB peptides that induce functional antibodies (CIIG)

PROJECT SUMMARY Neisseria gonorrhoeae (Ng) is an obligate human pathogen that causes gonorrhea, one of the most common sexually transmitted infections. The incidence of Ng infection in the United States is rising, and the emergence of multi-antibiotic resistant strains have led to fears that treatment options for gonorrhea are decreasing. The overall goal of the Center for Immunological Interventions against Gonorrhea (CIIG) is to advance promising approaches to combat Ng infection. In this project, our central hypothesis is that a vaccine targeting the immunomodulatory function of Ng will be an important component of a successful Ng vaccine. To accomplish this goal, we will develop vaccines that specifically target the Ng porin, PorB, a stably expressed, highly abundant surface protein that plays an important immunomodulatory role by binding to C4BP and factor H, negative regulators of the classical and alternative pathways of complement activation. In Aim 1, we will utilize a flexible and highly immunogenic vaccine platform technology that is based of bacteriophage virus-like particles (VLPs) to produce vaccines targeting loops of PorB that are involved in complement regulatory protein binding. In Aim 2, we will measure the immunogenicity of candidate vaccines and will evaluate the activity of induced antibodies. Vaccines that elicit antibodies that block C4BP and factor H binding will be evaluated for their ability to protect mice from Ng challenge both alone and in combination with optimal vaccine regimens developed elsewhere in the CIIG. In Aim 3 will focus on IND-enabling activities, including development of a comprehensive product development plan. These studies will benefit from extensive collaborations with the CIIG Core facilities and complement the vaccine and delivery development efforts of the other Projects.