Enhancing a live attenuated Francisella novicida vaccine for protection against Francisella tularensis

F. tularensis ssp tularensis is pathogenic Gram-negative facultative bacteria. It is the causative agent of tularemia with the pneumonia being the most fatal manifestation. The Center for Disease Control has labeled this Category A bio-threat a tier 1 select agent for its ease of dissemination and low infectious does. Currently there are no vaccines approved for use in the United States. Previous work from the lab of Karl E. Klose, Ph.D. utilized the avirulent F. novicida bacteria and generated a live attenuated vaccine by removing the function of a type 6 secretion system that contributes to its virulence in mice. The resulting strain, was named FniglD. Fn iglD vaccinated Fischer344 rats and cynomolgus macaques were protected against F. tularensis ssp tularensis infections. Although protection was high, complete protection was not consistent. The purpose of this study is to genetically manipulate Fnigld and modify the O-antigen of the lipopolysaccharide on the outer-surface of the bacteria to resemble the lipopolysaccharide of F. tularensis ssp tularenis. The resulting modifications were characterized, to determine if the protective immunity of FniglD can be enhanced.