Enhanced Immunogenicity and Protective Efficacy of a Campylobacter jejuni Conjugate Vaccine Coadministered with Liposomes Containing Monophosphoryl Lipid A and QS-21

Author:

Ramakrishnan Amritha1,Schumack Nina M.23,Gariepy Christina L.23,Eggleston Heather23,Nunez Gladys1,Espinoza Nereyda1,Nieto Monica1,Castillo Rosa1,Rojas Jesus1,McCoy Andrea J.1,Beck Zoltan4,Matyas Gary R.5,Alving Carl R.5,Guerry Patricia3,Poly Frédéric3,Laird Renee M.23

Affiliation:

1. Bacteriology Department, U.S. Naval Medical Research Unit No. 6, Callao, Peru

2. Henry M. Jackson Foundation for Military Medicine, Bethesda, Maryland, USA

3. Department of Enteric Diseases, Naval Medical Research Center, Silver Spring, Maryland, USA

4. U.S. Military HIV Research Program, Henry M. Jackson Foundation for Military Medicine, Bethesda, Maryland, USA

5. Laboratory of Adjuvant and Antigen Research, U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA

Abstract

Campylobacter jejuni is a leading cause of diarrheal disease worldwide, and currently no preventative interventions are available. C. jejuni is an invasive mucosal pathogen that has a variety of polysaccharide structures on its surface, including a capsule. In phase 1 studies, a C. jejuni capsule conjugate vaccine was safe but poorly immunogenic when delivered alone or with aluminum hydroxide. Here, we report enhanced immunogenicity of the conjugate vaccine delivered with liposome adjuvants containing monophosphoryl lipid A without or with QS-21, known as ALF and ALFQ, respectively, in preclinical studies. Both liposome adjuvants significantly enhanced immunity in mice and nonhuman primates and improved protective efficacy of the vaccine compared to alum in a nonhuman primate C. jejuni diarrhea model, providing promising evidence that these potent adjuvant formulations may enhance immunogenicity in upcoming human studies with this C. jejuni conjugate and other malaria and HIV vaccine platforms.

Funder

DOD | U.S. Navy

Publisher

American Society for Microbiology

Subject

Molecular Biology,Microbiology

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