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The development of vaccines to prevent Shigella infections

The University of Rome La Sapienza and the Pasteur Institute of Paris filed a patent application for industrial investment, titled "Shigella mutants in the functions pertaining to the processes of maturing and recycling peptidoglycans and their uses as immunogens".

The two institutes are partners in the FP5 project "The development of vaccines to prevent Shigella infections" ,(INNOVAX, contract No. QLK2-CT-1999-00938). The inventors are: Maria Lina Bernardini (University of Rome "La Sapienza", Dept Cell and Developmental Biology) and Philippe Sansonetti (Institut Pasteur of Paris, Unité de Pathogènie Microbienne Moléculaire).,Human resources were supported by INNOVAX and many students had the opportunity to share the knowledge and the expertise developed in this context. Shigellosis or bacillary dysentery is an intestinal disease that claims around 170 millions cases per year with 1 million of deaths. This disease mainly strikes impoverished people in developing countries. About 70% of the cases affects children between the ages of 1 and 5 years. Considering that about 2 millions of children less than five years old die each year throughout the world for diarrheic diseases it can be concluded that shigellosis accounts for one half of these deaths. Refugee camps or regions in the world where an inadequate water supply, poor sanitation, overcrowding, and malnutrition occur are exposed to the high risk of this unusually severe enteric infection. In industrialized world Shigella may cause outbreaks of diarrhea in day-care centers, military installations, institutions and cruise ships. ,The most important aspect of Shigellosis pathogenesis from a public health perspective is its extremely low infective dose, as low as 10-100 microorganisms, compared, for instance, to 10 millions of Salmonella microorganisms necessary to induce salmonellosis, another enteric disease. The spread of multidrug-resistant strains among the epidemic Shigella strains strengthens the need for new vaccines. The patent application includes 23 new Shigella mutants to be used as vaccines and as source of immunogenic molecules. The vaccine strains have been conceived to implement their immunogenic potential by improving the transition from innate to acquired immunity in the host along with the virulence attenuation. ,The vaccines have been extensively analyzed in suitable animal models - purposely developed in the course of the INNOVAX project - in order to determine their actual degree of virulence, to characterize their relevant features and, finally, to define a unique profile for each strain. At present, research on Shigella vaccine at the University of Rome proceeds in two innovative approaches. A first research line is aimed at characterizing the molecular mechanisms underlying the immune response provided by the individual vaccine strain. The other research line is finalized to construct a human vaccine based on some of the mutations identified during the INNOVAX project, following the rules established by the ethical committees. World Health Organization, that considers Shigella vaccine development first in line among priorities in the context of infectious diseases, partially funds this latter research line. The University of Rome La Sapienza and the Pasteur Institute of Paris are collaborating to these research lines.EU's Fifth Framework programme has greatly improved collaborative research and innovation in vaccine field.,The development of vaccines to prevent Shigella infections (INNOVAX) project was funded under FP5 with the objective to create a new generation of vaccines against Shigellosis and to improve collaboration among European laboratories with expertise in this field.,The results obtained include: basic knowledge improvement, animal model development and vaccine strains' construction.,Diarrheic diseases in developing countries is one of the main direct causes of death among children.,In refugee populations, epidemics of severe diarrheic diseases are commonly due to Shigella. ,Vaccine projects broaden basic knowledge of European Union Research institutions and promote industrial R&D and market-oriented innovation. Maria Lina Bernardini, PhD,Dip. Biologia Cellulare e dello Sviluppo,Sez. Scienze Microbiologiche,Universita "La Sapienza",Via dei Sardi 70 - 00185 Roma - Italy,Ph. ++ 39 06 49917579 - 4991 7850,Fax ++ 39 06 49917594,e-mail:


Research in vaccine field and vaccine development