Campylobacter jejuni is a Category B agent that is one of the major bacterial causes of diarrheal disease, and there are no vaccines available. The hypothesis of this project is that capsule conjugate vaccines can protect against diarrheal disease caused by Campylobacter jejuni. We have developed prototype capsule conjugate vaccines against two capsule types, that of the HS23, 36 serogroup and that of the HS4 serogroup. These vaccines were synthesized by conjugation of purified capsular polysaccharide of each serotype to CRM197, a diptheria toxoid used in licensed CPS-conjugate vaccines. Both of these vaccines showed significant protection against disease in a mouse intra-nasal model of infection. The HS23, 36 vaccine was also protected Aotus nancymae from diarrheal disease following 3 doses (25 micrograms each) administered intramuscularly. Based on these results we propose to develop methods for cGMP manufacture of the capsule from C. jejuni strain 81-176 (HS23, 36), conjugation to CRM197, and vialing of the product. The product would be characterized for chemical composition, safety, and immunogenicity in anticipation of IND submission for phase 1 human testing.
|Pequegnat, Brittany; Laird, Renee M; Ewing, Cheryl P et al. (2017) Phase-Variable Changes in the Position of O-Methyl Phosphoramidate Modifications on the Polysaccharide Capsule of Campylobacter jejuni Modulate Serum Resistance. J Bacteriol 199:|