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

• DOI: 10.1155/2018/8087916
• Publication Date: 2018-11-29T23:31:04Z
• Authors: Laura E. Marshall; Michelle Nelson; Carwyn H. Davies; Adam O. Whelan; Dominic C. Jenner; Madeleine G. Moule; Carmen Denman; Jon Cuccui; Timothy P. Atkins; Brendan W. Wren; Joann L. Prior
• Keywords: Mice, Inbred BALB C; 0303 health sciences; Vaccination; RC581-607; Rats, Inbred F344; Rats; 3. Good health; Disease Models, Animal; Mice; 03 medical and health sciences; Hexosyltransferases; Inhalation; Bacterial Vaccines; Pseudomonas aeruginosa; Animals; Humans; Female; Immunologic diseases. Allergy; Francisella tularensis; Glycoconjugates; Tularemia; Cells, Cultured; Research Article; Protein Binding

There is a requirement for an efficacious vaccine to protect people against infection fromFrancisella tularensis, the etiological agent of tularemia. The lipopolysaccharide (LPS) ofF. tularensisis 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 conjugateF. tularensisO-antigen glycans to the immunogenic carrier proteinPseudomonas aeruginosaexoprotein 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 ofF. tularensis. 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 withF. tularensisSchu S4. Our data highlights the potential of this biosynthetic approach for the creation of next-generation tularemia subunit vaccines.