A feasibility study to establish recruitment and immunmonitoring for a first in man study of a therapeutic H. pylori vaccine in healthy infected volunteers
H. pylori colonizes the stomach of about half of the world's population. The infection is acquired in early childhood and remains asymptomatic in the vast majority of infected individuals. Although the infection elicits a strong inflammatory response, the bacterium cannot be cleared by the immune system. This chronic infection is a prerequisite for the development of gastric adenocarcinomas, leading to considerable morbidity and mortality. The high prevalence of the infection and the rapid emergence of antibiotic resistance implicate the need for an H. pylori vaccine. IMX101 is a vaccine that is being developed for the treatment and prevention of infections with H. pylori. IMX101 is composed of two highly conserved recombinant Helicobacter antigens in combination with a potent mucosal adjuvant, which are administered via oral priming and systemic boost. A clinical phase I trial is planned to be initiated in October 2016.
A feasibility study was performed in Hamburg to establish the recruiting strategy, endoscopy, sampling and immunological assays in H. pylori-infected healthy subjects. A set of assays was established including biopsy sampling, serology, PCR, histopathology, T-cell activation and stool test.
During the feasibility study, 365 healthy volunteers were pre-screened by serology and urea breath test (UBT), and 27 subjects (n = 21 H. pylori positive, n = 6 H. pylori negative) fulfilling the criteria were enrolled and a full sampling screening was performed. The full screening program involved a urea breath test, H. pylori serology, upper GI endoscopy with biopsies from the stomach for cell culture, histology, qPCR and immunological analyses. A systematic biopsy sampling protocol including 25 biopsies was successfully performed in all subjects, allowing for direct comparison of local humoral and cellular immunity, colonization, and histology. Immunmonitoring assays were validated from blood samples.
This feasibility trial provided valuable knowledge for the planning of the phase I vaccination clinical trial, and enabled the optimization of the inclusion/exclusion criteria, recruitment strategy, sampling protocols and validation of immunmonitoring assays.