Related Experiment Video
Updated: Aug 29, 2025
Evaluation of Host-Pathogen Responses and Vaccine Efficacy in Mice
Published on: February 22, 2019
Evaluation of two different vaccine platforms for immunization against melioidosis and glanders
Sergei S Biryukov1, Christopher K Cote1, Christopher P Klimko1
1Bacteriology Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD, United States.
Abstract:
Burkholderia pseudomallei and the closely related species, Burkholderia mallei, produce similar multifaceted diseases which range from rapidly fatal to protracted and chronic, and are a major cause of mortality in endemic regions. Besides causing natural infections, both microbes are Tier 1 potential biothreat agents. Antibiotic treatment is prolonged with variable results, hence effective vaccines are urgently needed. The purpose of our studies was to compare candidate vaccines that target both melioidosis and glanders to identify the most efficacious one(s) and define residual requirements for their transition to the non-human primate aerosol model. Studies were conducted in the C57BL/6 mouse model to evaluate the humoral and cell-mediated immune response and protective efficacy of three Burkholderia vaccine candidates against lethal aerosol challenges with B. pseudomallei K96243, B. pseudomallei MSHR5855, and B. mallei FMH. The recombinant vaccines generated significant immune responses to the vaccine antigens, and the live attenuated vaccine generated a greater immune response to OPS and the whole bacterial cells. Regardless of the candidate vaccine evaluated, the protection of mice was associated with a dampened cytokine response within the lungs after exposure to aerosolized bacteria. Despite being delivered by two different platforms and generating distinct immune responses, two experimental vaccines, a capsule conjugate + Hcp1 subunit vaccine and the live B. pseudomallei 668 ΔilvI strain, provided significant protection and were down-selected for further investigation and advanced development.
Insights
Two experimental vaccines targeting melioidosis and glanders showed significant protection in mice against lethal aerosol challenges. These promising vaccines, a conjugate and a live attenuated strain, warrant further development for biodefense applications.
Area of Science:
- Microbiology
- Immunology
- Vaccinology
Background:
- * Burkholderia pseudomallei* and *Burkholderia mallei* cause severe diseases, including melioidosis and glanders, with high mortality in endemic areas.
- *B. pseudomallei* and *B. mallei* are classified as Tier 1 biothreat agents, necessitating urgent development of effective vaccines.
- Current antibiotic treatments for these infections are prolonged and yield variable results, highlighting the need for novel prophylactic strategies.
Purpose of the Study:
- * To compare the efficacy of three candidate vaccines against melioidosis and glanders.
- * To identify the most promising vaccine candidates for further development.
- * To define requirements for advancing these vaccines to non-human primate aerosol models.
Main Methods:
- * Evaluation of three *Burkholderia* vaccine candidates in the C57BL/6 mouse model.
- * Assessment of humoral and cell-mediated immune responses.
- * Determination of protective efficacy against lethal aerosol challenges with *B. pseudomallei* and *B. mallei* strains.
Main Results:
- * Recombinant vaccines induced significant immune responses to specific antigens.
- * A live attenuated vaccine elicited a stronger response to O-polysaccharide (OPS) and whole bacterial cells.
- * Protection in mice correlated with a reduced pulmonary cytokine response post-aerosol challenge.
- * Two vaccines, a capsule conjugate + Hcp1 subunit vaccine and a live attenuated *B. pseudomallei* strain, demonstrated significant protection.
Conclusions:
- * Two distinct vaccine platforms, a conjugate and a live attenuated strain, offer significant protection against *B. pseudomallei* and *B. mallei*.
- * These down-selected vaccines are suitable for further investigation and advanced development, including testing in non-human primate models.
- * The study identified key vaccine candidates for addressing melioidosis and glanders, crucial biodefense threats.
