Melhoramento de uma vacina multi-antigénica contra a Heliocobacter pylori

Abstract

Helicobacter pylori is a bacterium that colonizes the stomach about half the world’s population, being associated with increased risk of various diseases such gastritis, gastric and duodenal ulcers, mucosa-associated lymphoid tissue lymphomas and gastric adenocarcinomas. Emerging problems of the current therapy, based on antibiotics, makes the vaccine a promising alternative. However, the high genetic variability of this bacterium has hampered the development of efficient vaccines. A multi-antigenic vaccine could be a strategy to overcome this limitation and obtain a vaccine that represents globally the existing world strains. This work aims to improve an approach based on plasmid DNA and recombinant protein vaccine, consisting of multiple epitopes from different H. pylori antigens, and evaluate the ability to overcome the immune variability between different strains. To improve the vaccine was replaced the epitope of GroEL, due to its homology with human proteins, for a epitope of NapA, due to the relevance of this virulence factor in chronic infection. It was observed in the immunization studies in mice, with these two new constructions of vaccines (plasmid DNA and protein), an immune response. In Western blot we found that polyclonal antibodies generated during these immunizations recognized all protein extracts obtained from 15 H. pylori strains coming from different geographical regions and obtained from patients with various gastric disorders. The results confirm the potential of a multi-antigen vaccine to overcome the high immune variability of the H. pylori and and therefore this construction can form the basis of future vaccine H. pylori.

Date of Award	2014
Original language	Portuguese
Awarding Institution	Universidade Católica Portuguesa
Supervisor	Cecília R.C. Calado (Supervisor)