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Preclinical immunogenicity and protective efficacy of an oral Helicobacter pylori inactivated whole cell vaccine and multiple mutant cholera toxin: A novel and non-toxic mucosal adjuvant

Journal article
Authors Jan Holmgren
Stefan Nordqvist
Margareta Blomquist
Frida Jeverstam
Michael Lebens
Sukanya Raghavan
Published in Vaccine
Volume 36
Issue 41
Pages 6223-6230
ISSN 0264-410X
Publication year 2018
Published at Institute of Biomedicine, Department of Microbiology and Immunology
Pages 6223-6230
Language en
Links dx.doi.org/10.1016/j.vaccine.2018.0...
Keywords Helicobacter pylori, Whole cell vaccines, Adjuvants, Cytokines, regulatory t-cells, pylori infection, escherichia-coli, immune-responses, th17 responses, dmlt adjuvant, etec vaccine, immunization, safety, mice, Immunology, Research & Experimental Medicine
Subject categories Clinical immunology

Abstract

Mucosal vaccines against Helicobacter pylori consisting of either whole cell bacteria or recombinant antigens can induce immune protection against challenge in mice only when co-administrated with a strong mucosal adjuvant such as cholera toxin (CT) or Escherichia coli heat labile enterotoxin (LT). The strong enterotoxicity of these adjuvants however preclude their use in human vaccines. The recently developed multiple mutant CT (mmCT) is a strong, yet practically non-toxic novel mucosal adjuvant which here was admixed with a formalin-inactivated H. pylori whole cell vaccine (WCV) as a potential vaccine candidate against H. pylori infection. We report that intragastric immunizations with H. pylori WCV together with mmCT, similar to immunization with WCV together with CT, resulted in 50-125-fold reduction in colonization of H. pylori in the stomach of mice associated with rises in both serum IgG and intestinal-mucosal IgA anti-H. pylori antibody responses and strong T cell and IFN gamma and IL-17A cytokine responses. Data presented in this study also supports that the proposed vaccine can be grown in a bioreactor and would be effective against infection caused by a multitude of pathogenic H. pylori strains isolated from patients from various continents. The results warrant immunization studies in humans to evaluate the safety, immunogenicity and efficacy of the proposed H. pylori WCV and mmCT. (C) 2018 Published by Elsevier Ltd.

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