Yok Teng Chionh1, Arthi Arulmuruganar2, Elena Venditti3, Garrett Z Ng2, Jia-Xi Han2, Claire Entwisle3, Ching-Seng Ang4, Camilo A Colaco3, Shaun McNulty3, Philip Sutton5. 1. Mucosal Immunology, Murdoch Childrens Research Institute, Royal Children's Hospital, Melbourne, Parkville, VIC 3052, Australia; Centre for Animal Biotechnology, School of Veterinary Science, University of Melbourne, Parkville, VIC 3010, Australia. 2. Mucosal Immunology, Murdoch Childrens Research Institute, Royal Children's Hospital, Melbourne, Parkville, VIC 3052, Australia. 3. ImmunoBiology Ltd., Babraham Research Campus, Babraham, Cambridge, UK. 4. Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, VIC 3010, Australia. 5. Mucosal Immunology, Murdoch Childrens Research Institute, Royal Children's Hospital, Melbourne, Parkville, VIC 3052, Australia; Centre for Animal Biotechnology, School of Veterinary Science, University of Melbourne, Parkville, VIC 3010, Australia. Electronic address: phil.sutton@mcri.edu.au.
Abstract
BACKGROUND: The development of a vaccine against the human gastric pathogen Helicobacter pylori, the main causative agent of gastric adenocarcinoma, has been hampered by a number of issues, including the lack of a mucosal adjuvant for use in humans. Heat shock proteins (Hsp), highly conserved molecules expressed by both bacteria and mammalian species, possess a range of functions, including acting as chaperones for cellular proteins and the ability to activate innate immune receptors. Hsp complex (HspC) vaccines, containing Hsp derived from pathogenic bacteria, are immunostimulatory without addition of an exogenous adjuvant and can induce immunity against their chaperoned proteins. In this study we explored in mice the potential utility of a H. pylori HspC vaccine. RESULTS: Vaccination with H. pylori HspC, by either the subcutaneous or respiratory mucosal route, induced a strong antibody response, elevated gastric cytokine levels and significant protection against subsequent live challenge with this pathogen. The level of protection induced by non-adjuvanted HspC vaccine was equivalent to that which resulted from vaccination with adjuvanted vaccines. While protection induced by immunisation with adjuvanted vaccines was associated with the development of a moderate to severe atrophic gastritis, that induced by H. pylori HspC only resulted in a mild inflammatory response, despite an increase in pro-inflammatory gastric cytokines. This reduced gastritis correlated with an increase in IL-10 and IL-13 levels in the gastric tissues of HspC vaccinated, H. pylori challenged mice. CONCLUSIONS: H. pylori HspC vaccines have the potential to overcome some of the issues preventing the development of a human vaccine against this pathogen: HspC induced protective immunity against H. pylori without addition of an adjuvant and without the induction of a severe inflammatory response. However, complete protection was not obtained so further optimisation of this technology is needed if a human vaccine is to become a reality.
BACKGROUND: The development of a vaccine against the human gastric pathogen Helicobacter pylori, the main causative agent of gastric adenocarcinoma, has been hampered by a number of issues, including the lack of a mucosal adjuvant for use in humans. Heat shock proteins (Hsp), highly conserved molecules expressed by both bacteria and mammalian species, possess a range of functions, including acting as chaperones for cellular proteins and the ability to activate innate immune receptors. Hsp complex (HspC) vaccines, containing Hsp derived from pathogenic bacteria, are immunostimulatory without addition of an exogenous adjuvant and can induce immunity against their chaperoned proteins. In this study we explored in mice the potential utility of a H. pylori HspC vaccine. RESULTS: Vaccination with H. pylori HspC, by either the subcutaneous or respiratory mucosal route, induced a strong antibody response, elevated gastric cytokine levels and significant protection against subsequent live challenge with this pathogen. The level of protection induced by non-adjuvanted HspC vaccine was equivalent to that which resulted from vaccination with adjuvanted vaccines. While protection induced by immunisation with adjuvanted vaccines was associated with the development of a moderate to severe atrophic gastritis, that induced by H. pylori HspC only resulted in a mild inflammatory response, despite an increase in pro-inflammatory gastric cytokines. This reduced gastritis correlated with an increase in IL-10 and IL-13 levels in the gastric tissues of HspC vaccinated, H. pylori challenged mice. CONCLUSIONS:H. pylori HspC vaccines have the potential to overcome some of the issues preventing the development of a human vaccine against this pathogen: HspC induced protective immunity against H. pylori without addition of an adjuvant and without the induction of a severe inflammatory response. However, complete protection was not obtained so further optimisation of this technology is needed if a human vaccine is to become a reality.
Authors: Win-Yan Chan; Claire Entwisle; Giuseppe Ercoli; Elise Ramos-Sevillano; Ann McIlgorm; Paola Cecchini; Christopher Bailey; Oliver Lam; Gail Whiting; Nicola Green; David Goldblatt; Jun X Wheeler; Jeremy S Brown Journal: Infect Immun Date: 2019-02-21 Impact factor: 3.441
Authors: Win-Yan Chan; Claire Entwisle; Giuseppe Ercoli; Elise Ramos-Sevillano; Ann McIlgorm; Paola Cecchini; Christopher Bailey; Oliver Lam; Gail Whiting; Nicola Green; David Goldblatt; Jun X Wheeler; Jeremy S Brown Journal: Infect Immun Date: 2018-12-10 Impact factor: 3.609