Exploratory Program
The Exploratory Program is where the majority of the ‘upstream research’ takes place in NVGH. The main role of the program is to explore the potential for new vaccines against infectious diseases in the Developing World. Proposals for exploratory projects may originate either from within NVGH or from external collaborators. Such projects seek to address the following questions:
- The technical feasibility of producing the vaccine,
- The likelihood that the vaccine induces a protective immune response,
- The likelihood that a successful vaccine would make a significant impact on health.
The Exploratory Program offers opportunities for collaboration with academic institutions and for graduate student PhD research projects within NVGH. Current active collaborations involve Prof Gordon Dougan at the Wellcome Trust Sanger Institute, near Cambridge, UK; Prof Gerd Pluschke at the Swiss Tropical Public Health Institute, Basel, Switzerland; Prof Sam Kariuki, of the Kenyan Medical Research Institute, Nairobi; Prof Andrew Pollard, Director of the Oxford Vaccine Group, UK, and Prof Dan Granoff from the Children’s Hospital Oakland Research Institute, California, USA.
Currently, there are Exploratory Projects aimed at producing vaccines against:
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Neisseria meningitidis (also known as meningococcus) is responsible for devastating epidemics of meningitis in the African Meningitis Belt, which stretches from Senegal to the Horn of Africa. These epidemics can paralyse the fragile health systems of the countries they affect and occur on a background of meningococcal meningitis that is much higher than found in developed countries (Stephens DS et al, 2007). Although a vaccine has recently been introduced into Africa that can protect against the Serogroup A form of meningococcus, this is unable to help against meningitis caused by other serogroups, in particular Serogroups W-135 and X. As with NTS, two parallel vaccine approaches against meningococcus are currently under investigation at NVGH. One approach aims to produce a vaccine with broad coverage against current and future serotypes of meningococcus that cause meningitis epidemics within the African Meningitis Belt. The other is looking to specifically develop a vaccine specifically against meningococcus serogroup X, for which no vaccine is currently available. Stephen DS, et al. (2007.) Lancet 369: 2196-2210. |
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Nontyphoidal Salmonellae (NTS), particularly Salmonella enterica serovars Typhimurium and Enteritidis, are a major cause of bacterial blood stream infections and meningitis in sub-Saharan Africa (Reddy et al, 2011). Young children under two years of age, often also affected by malaria, anaemia, malnutrition or HIV infection, and HIV-infected adults are most susceptible. Case-fatality rates are over 20% and antibiotic resistance is an increasing problem. Together with difficulties in diagnosing NTS disease in Africa (many patients do not have diarrhea), this makes the need for a vaccine against NTS for Africa particularly urgent. Teams at NVGH are investigating two parallel vaccine approaches against NTS. With one, we are exploring the potential of a protein-based approach to produce a vaccine with broad coverage against a broad-range of Salmonella serovars and strains that cause invasive disease in the Developing World, particularly sub-Saharan Africa. The other approach is assessing the potential of O-Antigen glycoconjugates as vaccines against the two most common serovars responsible for NTS disease in Africa, serovars Typhimurium and Enteritidis. Reddy EA, et al. (2010.) Lancet Infect Dis 10: 417-432. |
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Shigella species are the major causative agents of bacillary dysentery. The World Health Organization estimates approximately 90 million cases of shigellosis per year of in developing countries with 100,000 deaths. Almost all deaths occur in developing countries and most of them in children under the age of five. Complications are especially common in malnourished children, with possible long-term consequences, including stunting and mental retardation in children experiencing multiple episodes. No vaccine is currently available and the prevalence of antibiotic resistance in Shigella isolates is increasing. Shigella is divided into 50 different serotypes by the outer polysaccharide (O antigen) of the lipoposysaccharide. The prevalence of these serotypes varies between regions and changes over time even within one region presenting a major challenge for vaccine development. The goal of NVGH’s Shigella vaccine project is to develop a low-cost, protein-based vaccine that is broadly protective against most, or ideally, all of the different Shigella serotypes. NVGH is working with various groups in the global community in Shigella research. The NVGH Shigella project has benefited from a grant from the Grand Challenges Explorations in Global Health of the Bill and Melinda Gates Foundation. Learn more about NVGH Shigella Project References: |
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