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Melioidosis

Melioidosis is a tropical infectious disease caused by the bacterium Burkholderia pseudomallei. At our company, we are committed to advancing the development of melioidosis vaccines and therapeutics through innovative research and collaboration, with the ultimate goal of providing customers with a one-stop solution.

Overview of Melioidosis

Melioidosis is a severe and potentially life-threatening infectious disease caused by the bacterium Burkholderia pseudomallei. This environmental pathogen is endemic to certain regions, particularly Southeast Asia and Northern Australia, where it is a major cause of sepsis and pneumonia. Melioidosis presents with a wide spectrum of manifestations, ranging from acute, fulminant disease to chronic, latent infections. The varied presentation and the inherent antibiotic resistance of B. pseudomallei make melioidosis a challenging infection to manage effectively.

Schematic diagram of milestones in the history of melioidosis.Fig.1 Milestones in the history of melioidosis. (Wiersinga W. J., et al., 2018)

Vaccine Development for Melioidosis

The development of a vaccine against melioidosis is a critical step in controlling this disease. Given the high morbidity and mortality rates associated with melioidosis, particularly in high-risk groups such as those with diabetes or compromised immune systems, a prophylactic vaccine could offer significant benefits.

Table 1 Vaccines for the prevention of melioidosis. (Johnson M. M., et al., 2017)

Vaccine Route of administration (vaccine/challenge) Challenge model (strain) Survival (%) post-challenge
Live attenuated
purN mutant (∆purN) i.n./i.p. B. pseudomallei (E8) 100% at day 9
purM mutant strain (∆purM/Bp82) SubQ/i.n. B. pseudomallei (1026b) 100% (C57BL/6) and 60% (BALB/c) at day 60
aroC mutant (∆aroC/A2) i.p./i.p. B. pseudomallei (A2) 80% (C57BL/6) and 0% (BALB/c) at 5 months
asd mutant (∆asd) i.n./i.n. B. pseudomallei (1026b) 100% at day 80 (acute infection); 0% at day 60 (chronic infection)
relA/spT mutant (∆relA/spT) i.n./i.n. B. pseudomallei (576) 100% at day 30 (C57BL/6)
Capsular polysaccharide (CPS)- expressing mutant B. thailandensis strain i.p./i.p. B. pseudomallei (K96243) 100% at day 35
Subunit
Purified outer membrane protein W (ompW) i.p./i.p. B. pseudomallei (576) 75% at day 21
Purified outer membrane protein 85 (omp85) i.p./i.p; B. pseudomallei (D286) 70% at day 15
Purified outer membrane vesicles (OMVs) i.p./i.p. B. pseudomallei (K96243) 67% at day 21
Purified MprA protein (SmBpF4) i.p./i.p. B. pseudomallei (D286) 100% at day 25
Purified LolC protein SubQ/i.p. B. pseudomallei (K96243) 80% at day 42
Purified PilV protein SubQ/SubQ B. pseudomallei (G207) NS
Purified proteins BPSL1897, BPSL3369, BPSL2287 i.p./i.p. B. pseudomallei (K96243) 75% at day 40
CPS and O-polysaccharide glycoconjugate (CPS2B1) SubQ/i.p. B. pseudomallei (K96243) 90% at day 21
OPS II glycoconjugate i.p./i.n. B. pseudomallei (K96243) 40% at day 14
Polymer-encapsulated adjuvant and whole-killed B. pseudomallei SubQ/i.p. B. pseudomallei (1026b) 88% at day 14
Cationic liposomes complexed with adjuvant and whole-killed B. pseudomallei i.m./i.p. B. pseudomallei (1026b) 100% at day 30
Cationic liposomes complexed with plasmid DNA and whole-killed B. pseudomallei i.n./i.n. B. pseudomallei (1026b) 100% at day 40

Therapeutics Development for Melioidosis

Therapy development for melioidosis has been challenging due to the intrinsic antibiotic resistance of B. pseudomallei. Current therapeutic options are limited to a few antibiotics with variable efficacy. The development of new drugs and therapies involves:

Drug Repurposing

Investigating drugs approved for other conditions for their potential activity against B. pseudomallei. This approach can expedite the development process, as the safety profiles of these drugs are already established.

Novel Antimicrobial Agents

Developing drugs that target specific virulence factors of B. pseudomallei, such as the type III secretion system or quorum sensing mechanisms, to inhibit bacterial pathogenicity.

Immunotherapies

Therapies that regulate the immune response of the host, such as cytokine inhibitors or enhancers, have the potential to be advantageous in controlling the condition.

Our Services

The development of effective vaccines and therapies is crucial to reducing the burden of this disease. Our services in the development of melioidosis vaccines and therapies are grounded in a deep understanding of the bacterium's biology and the host's immune response. We offer a comprehensive suite of services, including:

Disease Models

  • Mouse Models: BALB/c mice, C57BL/6 mice
  • Hamster Models: acute model of experimental melioidosis
  • Large Animal Models
  • Non-mammalian Models: nematode, amoeba

Preclinical Research

  • Drug Safety Evaluation
  • In Vivo Pharmacokinetics Study
  • In Vitro Pharmacokinetics Study
  • Activity Testing
  • Drug Resistance Evaluation

By leveraging our expertise in microbiology, immunology, and drug development, we are committed to advancing the field of melioidosis therapeutics and prevention. Through our preclinical research services and development programs, we strive to bring innovative solutions to the forefront of melioidosis therapeutics. If our services have piqued your interest, we warmly welcome you to reach out to us for further information and to obtain a detailed quotation for the services you require.

References

  1. Wiersinga W. J., et al. "Melioidosis." Nature reviews Disease primers 4.1 (2018): 1-22.
  2. Johnson Monica M., and Kristy M. Ainslie. "Vaccines for the prevention of melioidosis and glanders." Current tropical medicine reports 4 (2017): 136-145.

All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.