Glanders is a highly contagious and often fatal zoonotic disease caused by the bacterium Burkholderia mallei. The challenges associated with developing effective vaccines and therapies against this disease have been daunting, but our team of experts at our company remains steadfast in our pursuit of innovative solutions.
Overview of Glanders
Glanders primarily affects horses, mules, and donkeys, but can also infect humans through direct contact with infected animals or their secretions, or via inhalation of aerosolized bacteria. The disease manifests in both acute and chronic forms, with the acute presentation characterized by severe pneumonia, septicemia, and multi-organ abscesses. Even with appropriate antibiotic therapeutic, the mortality rate for acute glanders can reach 40-50%. The chronic form can lie dormant for years before reactivating, leading to potentially fatal relapses.
Fig. 1 Overview of the immunization and challenge strategy for direct comparison of Burkholderia vaccine candidates that were challenged with Bp K96243. (Biryukov S. S., et al., 2022)
Vaccine Development for Glanders
The development of glanders vaccines faces several unique challenges. Burkholderia mallei, the causative agent, is a Biosafety Level 3 (BSL-3) pathogen, requiring specialized laboratory facilities and safety protocols that can impede research progress. Additionally, the bacterium's ability to evade the host immune system and establish chronic, latent infections makes it particularly difficult to design vaccines that can provide robust, long-lasting protection against both acute and chronic forms of the disease. Nonetheless, there are already some Glanders vaccines in preclinical research.
Table 1 Glanders vaccines under preclinical development. (Johnson M. M., et al., 2017)
Vaccine |
Route of administration (vaccine/challenge) |
Challenge model (strain) |
Survival (%) post-challenge |
Live attenuated |
tonB/hcp1 mutant (∆tonB/hcp1 CLH001) |
i.n./i.n. |
B. mallei (CSM001) |
100% survival at day 35 |
B. mallei |
tonB mutant (∆tonB/TMM001) |
i.n./i.n. |
B. mallei (CSM001) and B. pseudomallei (K96243) |
100% at day 28; 75% at day 36 |
tssN mutant strain (∆tssN/BMAA0728) |
aerosol/aerosol |
B. mallei |
67% at day 21 |
Subunit |
Gold nanoparticles (AuNPs) glycoconjugates (TetHc, Hcp1, FliC) |
i.n./i.n. |
B. mallei |
90% (TetHc; Hcp1) and 60% (FliC) at day 21 |
AuNP glycoconjugates (LPS-FliC) |
Aerosol/aerosol |
B. mallei |
50% at day 80 (Rhesus macaque) |
Therapeutics Development for Glanders
Antibiotic therapy is a cornerstone of glanders therapeutics. In vitro susceptibility testing has identified several potential agents, but in vivo efficacy is complicated by the bacterium's ability to evade host immune responses and resist antibiotic penetration. Notable among the antibiotics that have shown promise are doxycycline, imipenem, and sulfadiazine. Combination therapies are often used to enhance efficacy and prevent the development of resistance.
Additionally, our researchers have been investigating alternative antimicrobial approaches, such as the use of antibiotic-loaded nanoparticles, antimicrobial peptides, and host-directed therapies that can potentiate the immune system's ability to clear B. mallei infections. Please click on the link below to learn more about our one-stop therapy development solutions.
Our Services
At our company, we are committed to advancing the fight against glanders through the development of innovative vaccine and therapy solutions. Our multidisciplinary team of experts, including microbiologists, immunologists, and formulation scientists, is dedicated to exploring cutting-edge approaches to combat this rare but deadly infectious disease.
Infectious Disease Models
- Mouse Models: Intraperitoneal inoculation with either a sublethal or a lethal dose of Burkholderia mallei
- Equine Models: Intratracheal deposition of Burkholderia mallei to produce clinical glanders
By harnessing the power of live attenuated strains, subunit antigens, and combination therapies, we are working tirelessly to unlock the key to long-lasting protection and effective therapeutic against glanders. 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
- Biryukov, Sergei S., et al. "Evaluation of two different vaccine platforms for immunization against melioidosis and glanders." Frontiers in Microbiology 13 (2022): 965518.
- Johnson, Monica M., and Kristy M. Ainslie. "Vaccines for the prevention of melioidosis and glanders." Current tropical medicine reports 4 (2017): 136-145.
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only and cannot be used to diagnose, treat or manage patients.