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

The frequency of circulating integrin α4β7+ cells correlates with protection against Helicobacter pylori infection in immunized mice

“…In the current study, we have evaluated immune correlates in the blood to vaccine-induced protection against H pylori infection. We were able to confirm previous findings that the non-toxic adjuvant mmCT was as effective as an adjuvant as native CT in a H pylori vaccine for enhancing antigen-specific T-cell responses and cytokine secretion 14 and report several important new findings, namely that (a) the populations of innate and memory cells are increased in the circulation after vaccination and that (b) the frequency of α4β7 + CD4 + T cells emerging in the blood after 1st and 2nd immunization, irrespective of route or adjuvant correlated inversely with the bacterial load in the stomach of mice. We believe that the results from this study will be useful for the design of a H pylori vaccine and the evaluation of vaccine efficacy in clinical trials.…”

“…A detailed mechanism of adjuvant activity of mmCT has also been recently demonstrated in human in vitro activated co‐cultures of T cells and antigen‐presenting cells . Furthermore, preclinical studies have shown that mmCT is as effective as CT in promoting mucosal and systemic immune responses to the co‐administered model antigen ovalbumin and a H pylori whole cell vaccine and thus seems to be a promising mucosal adjuvant …”

“…Groups of mice were immunized sublingually twice at a bi‐weekly interval with 200 μg of H pylori lysate antigens reconstituted in 7.5 μg of CT or 15 μg of mmCT on each occasion (hereafter referred to as SL + CT or SL + mmCT) (Figure A). H pylori vaccination regimen (route and vaccine) was carefully chosen based on our previous studies …”

“…H pylori vaccination regimen (route and vaccine) was carefully chosen based on our previous studies. 14,18…”

“…13 Furthermore, preclinical studies have shown that mmCT is as effective as CT in promoting mucosal and systemic immune responses to the co-administered model antigen ovalbumin and a H pylori whole cell vaccine and thus seems to be a promising mucosal adjuvant. 14 During vaccination, dendritic cells can take up the vaccine antigens from the delivery site and migrate to the draining lymph node for presentation and activation of CD4 + T cells. Activated and differentiated CD4 + T cells can then migrate back to the mucosal sites including stomach and intestine via the blood guided by the expression of the mucosal tissue-specific integrin molecule α4β7 which binds to the endothelial cell adhesion molecule, mucosal vascular addressin cell adhesion molecule 1 (MAdCAM-1).…”