Application of a Campylobacter jejuni mouse infection model to test efficacy of a C. jejuni capsule conjugate vaccine delivered with a potent liposome adjuvant containing monophosphoryl lipid A and QS-21

Abstract

Abstract Campylobacter jejuni is a major cause of infectious diarrhea worldwide. Increasing incidence of C. jejuni is attributed to new non-culture based detection methods and antibiotic resistance is unfortunately on the rise, necessitating development of interventions. Therapeutics development like vaccines have been hampered by lack of a small animal model that recapitulates campylobacteriosis symptoms. To better facilitate vaccine efficacy testing, we adapted a recently-published mouse C. jejuni infection model to adult mice fed a zinc-deficient diet and pre-treated with antibiotics prior to oral infection with C. jejuni strain 81–176. Non-vaccinated infected mice develop diarrhea, lose weight and show increased expression of fecal inflammatory markers indicating development of campylobacteriosis. We tested whether an 81–176 C. jejuni capsule conjugate vaccine delivered with a potent liposome adjuvant containing monophosphoryl lipid A and QS-21 known as ALFQ could protect mice against 81–176. Vaccinated mice developed high levels of anti-CPS IgG1 and IgG2b titers and serum bactericidal responses against 81–176. Vaccinated infected mice were protected against development of diarrhea, did not lose weight, and had significantly lower levels of fecal inflammatory marker expression. Importantly, vaccinated infected animals were protected against C. jejuni colonization indicating that parenteral vaccination with a conjugate vaccine plus the ALFQ adjuvant may provide protection against both C. jejuni disease and colonization. These promising results support further development of a multivalent C. jejuni conjugate vaccine platform delivered with potent adjuvant systems for use in human clinical studies.