Combining vaccination and postexposure CpG therapy provides optimal protection against lethal sepsis in a biodefense model of human melioidosis
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Updated: May 30, 2026
Protective Efficacy and Pulmonary Immune Response Following Subcutaneous and Intranasal BCG Administration in Mice
Published on: September 19, 2016
Anna Easton1, Ashraful Haque, Karen Chu
1Centre for Clinical Microbiology, Royal Free Campus University College London, United Kingdom.
Abstract:
The Gram-negative bacterium Burkholderia pseudomallei is the causative agent of melioidosis, a major cause of lethal sepsis and morbidity in endemic areas of Southeast Asia and a potential bioterrorism threat. We have used susceptible BALB/c mice to evaluate the potential of targeting vaccination and generic immunotherapy to the lung for optimal protection against respiratory challenge. Intranasal vaccination with live attenuated B. pseudomallei increased survival and induced interferon-γ-secreting T cells in the lung. Intranasal delivery of CpG oligodeoxynucleotides also provided significant protection; however, combining preexposure vaccination with CpG treatment at the time of infection or up to 18 hours after infection, provided significantly greater protection than either treatment alone. This combination prolonged survival, decreased bacterial loads by >1000-fold, and delayed the onset of sepsis. This novel approach may be applicable to other potential biodefense agents for which existing countermeasures are not fully effective.
Insights
This study shows that combining intranasal vaccination against Burkholderia pseudomallei with CpG immunotherapy significantly enhances protection against melioidosis. This approach offers improved survival and reduced bacterial load in mice, suggesting a novel strategy for biodefense.
Area of Science:
- Immunology
- Microbiology
- Infectious Diseases
Background:
- Burkholderia pseudomallei causes melioidosis, a severe disease in Southeast Asia and a bioterrorism concern.
- Effective countermeasures against B. pseudomallei infection are limited.
Purpose of the Study:
- To evaluate intranasal vaccination and immunotherapy for protection against respiratory B. pseudomallei challenge.
- To determine if combining vaccination with CpG oligodeoxynucleotides improves outcomes.
Main Methods:
- BALB/c mice were used to test intranasal vaccination with live attenuated B. pseudomallei.
- CpG oligodeoxynucleotides were administered intranasally as immunotherapy.
- Mice were challenged with B. pseudomallei via respiratory route.
Main Results:
- Intranasal vaccination increased survival and induced lung T cell responses.
- CpG immunotherapy alone provided significant protection.
- Combination therapy markedly improved survival, reduced bacterial load (>1000-fold), and delayed sepsis onset.
Conclusions:
- Combined intranasal vaccination and CpG immunotherapy offer superior protection against B. pseudomallei.
- This strategy presents a promising novel approach for melioidosis and other biodefense threats.
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