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Protection of non-human primates against glanders with a gold nanoparticle glycoconjugate vaccine
Alfredo G Torres1, Anthony E Gregory2, Christopher L Hatcher3
1Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA; Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA.
Abstract:
The Gram-negative Burkholderia mallei is a zoonotic pathogen and the causative agent of glanders disease. Because the bacteria maintain the potential to be used as a biothreat agent, vaccine strategies are required for human glanders prophylaxis. A rhesus macaque (Macaca mulatta) model of pneumonic (inhalational) glanders was established and the protective properties of a nanoparticle glycoconjugate vaccine composed of Burkholderia thailandensis LPS conjugated to FliC was evaluated. An aerosol challenge dose of ∼1×10(4) CFU B. mallei produced mortality in 50% of naïve animals (n=2/4), 2-3 days post-exposure. Although survival benefit was not observed by vaccination with a glycoconjugate glanders vaccine (p=0.42), serum LPS-specific IgG titers were significantly higher on day 80 in 3 vaccinated animals who survived compared with 3 vaccinated animals who died. Furthermore, B. mallei was isolated from multiple organs of both non-vaccinated survivors, but not from any organs of 3 vaccinated survivors at 30 days post-challenge. Taken together, this is the first time a candidate vaccine has been evaluated in a non-human primate aerosol model of glanders and represents the initial step for consideration in pre-clinical studies.
Insights
A novel nanoparticle glycoconjugate vaccine showed no survival benefit against glanders disease in a non-human primate model. However, vaccinated survivors exhibited higher antibody titers and reduced bacterial load, suggesting potential for further development.
Area of Science:
- Microbiology
- Immunology
- Vaccinology
Background:
- Burkholderia mallei is a Gram-negative zoonotic pathogen causing glanders.
- Glanders poses a biothreat risk, necessitating human prophylaxis strategies.
- A rhesus macaque model for inhalational glanders was established.
Purpose of the Study:
- To evaluate the efficacy of a nanoparticle glycoconjugate vaccine against B. mallei.
- To assess vaccine-induced immune responses in a non-human primate model.
Main Methods:
- A nanoparticle vaccine (B. thailandensis LPS conjugated to FliC) was tested.
- Rhesus macaques were challenged via aerosol with B. mallei.
- Survival, antibody titers, and bacterial dissemination were monitored.
Main Results:
- The vaccine did not improve survival rates (p=0.42).
- Vaccinated survivors had significantly higher LPS-specific IgG titers.
- B. mallei was not isolated from organs of vaccinated survivors, unlike unvaccinated animals.
Conclusions:
- This study is the first to evaluate a glanders vaccine candidate in a non-human primate aerosol model.
- The vaccine induced an immune response, indicated by higher antibody titers and reduced bacterial load in survivors.
- Further pre-clinical studies are warranted to optimize this vaccine strategy.
