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Burkholderia vaccines

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Burkholderia are uniquely dangerous pathogens and biodefense threats. Currently, B. mallei and B. pseudomallei are considered category B Select Agents. Both bacteria are capable of causing rapidly fatal disease in humans. Burkholderia mallei is a pathogen primarily of equidae (donkeys, horses) that has no ...

Burkholderia are uniquely dangerous pathogens and biodefense threats. Currently, B. mallei and B. pseudomallei are considered category B Select Agents. Both bacteria are capable of causing rapidly fatal disease in humans. Burkholderia mallei is a pathogen primarily of equidae (donkeys, horses) that has no natural reservoir other than infected animals. In contrast, B. pseudomallei is primarily a soil microorganism that can infect humans if inhaled, ingested, or introduced into the skin. Both bacteria are endemic in certain parts of the world, with B. pseudomallei infection being widespread throughout Southeast Asia and northern Australia. Indeed, the range of B. pseudomallei appears to be increasing, with endemic infections now documented in India, China, Brazil, and parts of Central America. The mortality rate for humans infected with B. pseudomallei is over 90% if untreated and approaches 50% even with antibiotic therapy .

Several features of Burkholderia make these particularly dangerous pathogens relative to other bacterial agents. Both bacteria are extremely virulent when inhaled, inducing rapidly fatal pneumonia; and both can also cause oral and cutaneous infections. In addition, both organisms exhibit high levels of intrinsic antibiotic resistance, thereby limiting treatment choices to only a few antimicrobials. Burkholderia readily establishes persistent, disseminated infection (lymph nodes, spleen, liver, skin, brain, joints) that may persist for decades before reactivation of infection. Prolonged, aggressive and high-dose therapy is required to fully eradicate these organisms. Notably, B. pseudomallei can be readily cultured from soil and water in endemic regions, making it very easy to obtain cultures of the organism. Thus, Burkholderia species possess a number of unique features that make these bacteria particularly dangerous pathogens and high-risk bioweapons.

Development of new Burkholderia vaccines. Vaccination is a logical approach to reducing the risk of deliberate or accidental Burkholderia infection, given the challenges associated with relying only on antimicrobial therapy. Thus, there have been several attempts to develop Burkholderia vaccines, with most of the efforts directed towards vaccines against B. pseudomallei. To date, most work on Burkholderia vaccines has focused on use of live-attenuated bacterial vaccines . While live, attenuated vaccines generally induce more effective immunity than subunit or killed bacterial vaccines, live attenuated vaccines are more difficult to produce and store and entail risks related to reversion to virulence and adverse effects in immunosuppressed individuals. There have been fewer attempts to develop subunit vaccines against B. pseudomallei, though protection has been achieved with a vaccine that used the ABC transporter protein LolC, with dendritic cells pulsed with heat-killed Burkholderia, a DNA vaccine encoding flagellin (16-20), and two recently published studies involving our group using Burkholderia thailandensis LPS and four protein antigens. To date, the use of multivalent subunit vaccines to elicit protection and/or cross-protection from Burkholderia is a highly under-exploited area of research.


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