Program Director/Principal Investigator: Schryvers, Anthony B.
Neisseria gonorrhoeae, the bacterial pathogen that causes gonorrhea, is now considered an “Urgent Threat”
due to the recent emergence of strains with multi-drug resistance to the antibiotics that are frequently used
during treatment. Due to the emergence of these `superbug' strains, we are progressing towards the spread of
untreatable gonococcal infections. This situation has added to the urgency for developing a vaccine to prevent
these infections, as untreated gonococcal infections can lead to pelvic inflammatory disease, ectopic
pregnancy, infertility and invasive infections. Development of a gonococcal vaccine has been challenging due
to the remarkable ability of the bacterium to vary its surface components and suppress the development of a
protective immune response against reinfection in humans, and due to the lack of appropriate animal models
available to study infection and immunity of this pathogen. The primary focus of this proposal is to further
develop a protein-based vaccine that targets the constitutively-expressed gonococcal transferrin binding
protein B (TbpB), which captures iron from human transferrin. It is an ideal target since the transferrin receptor
in N. gonorrhoeae is required for survival on the mucosa and we have shown that it is capable of reducing
colonization in a mouse model. We have demonstrated that transferrin-binding defective mutants of TbpB
induce a more protective immune response than the wild type proteins, and are currently finalizing the
antigenic composition of our TbpB-based vaccine. In this project, we will scale-up and optimize production and
purification of our antigens, develop an optimal vaccine formulation and perform all the steps required for
implementing Phase I trials in humans. Cross-protection will be evaluated in a lower genital tract colonization
model and a model of pelvic inflammatory disease using female transgenic mice expressing human CEACAM
receptors and human transferrin, which facilitate gonococcal mucosal attachment and growth, respectively.
Together with an industrial sponsor, Vaxiron, Inc., we will develop quality control tools and metrics for
assessing vaccine antigen formulations, transfer production of our vaccine formulation to a contract
manufacturing organization, complete all the quality, stability and toxicology studies required for regulatory
approval to proceed to a future Phase I clinical trial after the culmination of this project.