Development of a porin-based anti-Salmonella multi-valent vaccine formulation for non-invasive immunisation

Constantino III Roberto López-Macías

Professor Constantino III Roberto López-Macías 
Principal Investigator
Medical Research Unit of Immunochemistry (Mexico) 

Collaborators:

Professor Yvonne Perrie, Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde (UK)
Professor Sevda Senel, Hacettepe University, Faculty of Pharmacy Department of Pharmaceutical Technology (Ankara-Turkey) 

Summary

Salmonella infections in humans are the cause of enteric fevers (Typhoid (TF) and Paratyphoid (PT)) and Non-Typhoidal Salmonellosis (NTS), which are major causes of morbidity and mortality in developing countries. There are no commercially available vaccines for PT and NTS and current vaccines for TF do not offer effective control of the disease. Thus a multi-valent vaccine that protects against all the different clinical manifestations remains an unmet public health need. Porins are outer membrane proteins from Salmonella enterica that generate immune responses in acute and convalescent TF and NTS patients. Purified porins have shown promise as a multivalent vaccine in preclinical testing and have also been shown to be safe and well tolerated in human volunteers. In addition, volunteers who received the porin-based vaccine carry circulating bactericidal antibodies up to 10 years after receiving one single immunisation. So far the porin-based vaccine formulation has been tested using conventional systemic delivery. In addition to being a non-invasive method for vaccine administration, mucosal delivery has the potential of eliciting protective immune responses at the pathogen site of entry. However, mucosal vaccination requires potent adjuvants and delivery systems to enhance immunogenicity, and to decrease the degradation rate. Particulate delivery systems such as micro/nano particles and liposomes have the ability to protect and carry subunit antigens to mucosal inductive sites. We aim to formulate particulate delivery systems for a porin multivalent vaccine for mucosal administration.