CREATING A MULTIVALENT SUBUNIT VACCINE USING TYPE III SECRETION SYSTEM TIP PROTEINS AS ANTIGENS

Abstract

Many gram-negative bacterial pathogens employ type III secretion systems (TTSS) to transport effector proteins into eukaryotic host cell membranes and cytoplasms to subvert normal cellular functions. TTSSs contain a basal body which spans the inner and outer bacterial membranes and a needle which extends the into extracellular space. With the increasing prevalence of drug resistant bacterial strains, vaccines represent one of the most promising strategies to combat these diseases. Proteins located at the extracellular needle tip of TTSSs appear to be excellent candidates for a sub-unit vaccine approach. These so called tip proteins are surface exposed and regulate the secretion of other effector proteins. This work presents pre-formulation, formulation and animal studies focused on creating a single multivalent sub-unit vaccine for five gram-negative pathogenic systems. In addition, a putative tip protein from Chlamydiae is compared to the other tip proteins using biophysical methods.