Development of a new prophylactic vaccine against Helicobacter pylori

Short description

Helicobacter pylori is one of the top 10 bacterial threats listed by the WHO, for which treatment is becoming increasingly difficult due to rising antibiotic resistance. More than half of the world's population is chronically infected with this bacterium. H. pylori is a recognised class I carcinogen responsible for at least 750,000 cases of gastric cancer each year. The project aims to further develop a vaccine against H. pylori. This approach is based on a selection of newly identified surface proteins as vaccine candidates that are prioritised in vivo for immunogenicity and protective efficacy. Subsequently, the protein vaccine is optimised in its composition, formulation, and application. In addition, studies with new vaccine approaches (RNAs, viral vectors) will be conducted and successful approaches compared and combined with the protein vaccine to define a preclinical candidate. This candidate will then be further developed via preclinical and toxicity studies up to clinical trials.

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One of the major challenges of this project is to identify effective mucosal adjuvant formulations with the potential to enhance mucosal immune response. So far, there are only a few mucosal adjuvants available that can also be used in humans. We are currently studying new promising mucosal adjuvants in a prophylactic vaccination setting where mice are immunised to induce local humoral and cellular immune responses against H. pylori. However, the induction of gastrointestinal mucosal immunity may influence the gut microbiome, and such alterations may be considered a relevant side effect from a regulatory perspective. In addition, such alterations may have supportive but also ameliorating effects on the efficacy of vaccination. Therefore, by 16S rRNA gene sequencing, we aim to study whether and to what extent these immunostimulatory mucosal adjuvants have the potential to change the microbial composition upon prophylactic vaccination.

We are further studying the H. pylori genomic diversity under vaccine-induced selective (immune) pressure in order to exclude immune evasion by antigen loss or non-synonymous mutations. To this end, H. pylori strains from the mouse models used to evaluate our vaccine candidates will be studied by genome sequencing, methylome analysis and transcriptome analysis. In this way, we seek to understand and quantify the selective (immune) pressure exerted by the prophylactic vaccine candidates.