Burkholderia pseudomallei and Burkholderia mallei vaccines: Are we close to clinical trials?
Section snippets
Melioidosis; The global incidence
B. pseudomallei is the cause of melioidosis, a serious and often fatal disease of humans and animals. The closely related bacterium B. mallei, which causes glanders, is a clonal derivative of B. pseudomallei [1], with a reduced host range. In this review we have included references to B. mallei where appropriate. Human melioidosis can range from a localised skin infection to an acute septicaemia or a pneumonia. Some individuals develop chronic disease, whilst others apparently clear the
Live attenuated vaccines
A range of attenuated B. pseudomallei (and B. mallei) mutants able to induce protective immunity in mice have been reported [14], [20], [21], [22], [23], [24], [25], [26]. However, not all attenuated mutants can induce protective immunity. Some are over-attenuated and are cleared too rapidly or the disrupted gene may play a role in biosynthesis of a protective antigen [27]. Immunisation with Burkholderia thailandensis, a naturally attenuated species that is related to B. pseudomallei can induce
Criteria for candidate selection
An efficacious melioidosis/glanders vaccine would ideally provide high level protection against multiple routes of infection, protect against multiple LPS types and provide sterilizing immunity. Additionally, it would be both safe and cost-effective to produce. At present, some of the most promising vaccine candidates undergoing pre-clinical evaluation include LPS- and CPS-based glycoconjugates, protein sub-units, OMVs and live attenuated strains. Important properties associated with these
Correlates of protection
All vaccine discovery and evaluation projects benefit from an understanding of the immune responses underlying protection. The term ‘immunological correlates of protection’ describes an immunological response, typically measured by laboratory assay, which is statistically associated with vaccine efficacy and based on clinical trial data in humans [85], [86]. Correlates of protection may be mechanistic, where the response measured directly mediates protection, or non-mechanistic serving as an
Conclusion
There have been a number of important developments since the publication of previous reviews on the development of B. pseudomallei and B. mallei vaccines. In this review we highlight the DTRA guidelines on vaccine performance, and which might drive any assessment of the candidates which could be selected for development and clinical trials. These criteria might be equally applicable to vaccines for biodefence and public health purposes. We also consider some of the important the criteria for
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