An O-Antigen Glycoconjugate Vaccine Produced Using Protein Glycan Coupling Technology Is Protective in an Inhalational Rat Model of Tularemia

Abstract

There is a requirement for an efficacious vaccine to protect people against infection from <i>Francisella tularensis</i>, the etiological agent of tularemia. The lipopolysaccharide (LPS) of <i>F. tularensis</i> is suboptimally protective against a parenteral lethal challenge in mice. To develop a more efficacious subunit vaccine, we have used a novel biosynthetic technique of protein glycan coupling technology (PGCT) that exploits bacterial N-linked glycosylation to recombinantly conjugate <i>F. tularensis</i> O-antigen glycans to the immunogenic carrier protein <i>Pseudomonas aeruginosa</i> exoprotein A (ExoA). Previously, we demonstrated that an ExoA glycoconjugate with two glycosylation sequons was capable of providing significant protection to mice against a challenge with a low-virulence strain of <i>F. tularensis</i>. Here, we have generated a more heavily glycosylated conjugate vaccine and evaluated its efficacy in a Fischer 344 rat model of tularemia. We demonstrate that this glycoconjugate vaccine protected rats against disease and the lethality of an inhalational challenge with <i>F. tularensis</i> Schu S4. Our data highlights the potential of this biosynthetic approach for the creation of next-generation tularemia subunit vaccines.