Burkholderia pseudomallei is a pathogen that infects humans causing melioidosis, a non-transmissible disease resulting in high mortality and morbidity.
Evidence is evolving to suggest that B. pseudomallei is present in many tropical and sub-tropical regions of the world (Limmathurotsakul 2016, Currie 2008). Identification and diagnosis are problematic due to non-specific symptoms of infection and inaccurate identification because of cross reactivity with closely related environmental bacteria. Treatment of infection can be ineffective due to inherent antibiotic resistance of the pathogen resulting in lengthy treatment regimes with high rates of failure. B. pseudomallei is designated as a select agent by the centre for disease control because of its potential as a bioweapon and its ability to cause lethal disease in humans and animals.
The challenges of developing a Melioidosis vaccine
Developing an effective B. pseudomallei vaccine is a considerable challenge. There are several different types of vaccine in the research phase, demonstrating varying levels of efficacy in a number of animal models. Progress in the B. pseudomallei vaccine field of research is impeded by the lack of an agreed animal vaccine challenge model. This results in generation of data from a number of different laboratories that cannot be directly compared. There is a requirement for both a public health and military vaccine. In the public health case the vaccine would need to protect humans against infection from ingestion, aerosolisation or subcutaneous injection of the pathogen, whereas the most likely route of exposure in a military scenario would be by aerosolisation.
In order to progress a potential B. pseudomallei vaccine it may be that the ‘animal rule’ to obtain licensure would be used. This requires that animal efficacy data is compiled along with human safety data to progress a vaccine to licensure. This is because it may be difficult to generate sufficient data for a phase 3 trial in the disparate at risk human population.
Further challenges include:
Lack of immune correlates
For some vaccines, the level and particular kind of immune response that is needed for the vaccine to work – i.e. to stop someone getting disease, is known. For melioidosis, we do not know what kind of immune response is needed, let alone what level of response is required.
Uncertain predictive value of animal models
It is not possible to test a vaccine in humans without testing it first in animals. However, we do not know which, if any, of the animal models to assess B. pseudomallei vaccines best predicts efficacy in humans. This means we can only determine if a vaccine will evoke a potentially appropriate immune response in humans by immunogenicity testing.
Difficulty of working with B. pseudomallei in the lab
B. pseudomallei is a highly infectious pathogen, which means we can only safely work with it in the lab using special containment measures (called Category or BSL 3). This limits the number of laboratories that can work on B. pseudomallei.
How VALIDATE will help
By bringing together researchers working on different (but similar) pathogens, discoveries in one field can be more quickly taken advantage of in research against another pathogen. Bringing together researchers from different disciplines and institutes in new collaborations means knowledge can be exchanged and new research ideas for the field can be generated and investigated. Bringing new researchers into this field, and progressing the careers of early career researchers, will aid with new ideas and the continuation of the field into the future.
There are several reviews available on the internet and the ‘Melioidosis.info’ webpages have a lot of useful information.
Limmathurotsakul D et al. Predicted global distribution of Burkholderia pseudomallei and burden of melioidosis. Nat Microbiol 2016;1:15008.
Currie BJ, et al. The global distribution of Burkholderia pseudomallei and melioidosis: an update. Trans R Soc Trop Med Hyg 2008;102 (Suppl 1):S1–4.