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 Gonorrhea Vaccine Cooperative Research Center (GV CRC) is to identify promising new vaccine candidates for Ng. In this project, our central hypothesis is that an effective gonorrhea vaccine can be developed by engineering highly immunogenic vaccines that specifically target critical surface-exposed Ng epitopes. To do this, we will utilize a flexible and highly immunogenic vaccine platform technology that is based of bacteriophage virus-like particles (VLPs). In Aim 1, we will engineer VLP-based vaccines that target surface- exposed epitopes of four Ng antigens that are potential vaccine targets. In Aim 2, we will measure the immunogenicity of candidate vaccines and assess the bactericidal and opsonophagocytic activity of induced antibodies. In Aim 3, we will test the efficacy of the most promising VLP vaccines in challenge studies using mouse genital tract infection models. These studies will benefit from extensive collaborations with the GV CRC Core facilities and complement the vaccine development efforts of the other Projects.