Open AccessEvaluation of Burkholderia mallei ΔtonB Δhcp1 (CLH001) as a live attenuated vaccine in murine models of glanders and melioidosis
Author(s) -
Nittaya Khakhum,
Preeti Bharaj,
Julia N. Myers,
Daniel Tapia,
David H. Walker,
Janice J. Endsley,
Alfredo G. Torres
Publication year - 2019
Publication title -
plos neglected tropical diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.99
H-Index - 135
eISSN - 1935-2735
pISSN - 1935-2727
DOI - 10.1371/journal.pntd.0007578
Subject(s) - melioidosis , microbiology and biotechnology , burkholderia pseudomallei , biology , burkholderia , immune system , virology , vaccination , attenuated vaccine , immunology , bacteria , virulence , biochemistry , genetics , gene
Background Glanders caused by Burkholderia mallei is a re-emerging zoonotic disease affecting solipeds and humans. Furthermore, B . mallei is genetically related to B . pseudomallei , which is the causative agent of melioidosis. Both facultative intracellular bacteria are classified as tier 1 select biothreat agents. Our previous study with a B . mallei Δ tonB Δ hcp1 (CLH001) live-attenuated vaccine demonstrated that it is attenuated, safe and protective against B . mallei wild-type strain s in the susceptible BALB/c mouse model. Methodology/Principal finding In our current work, we evaluated the protective efficacy of CLH001 against glanders and melioidosis in the more disease-resistant C57BL/6 mouse strain. The humoral as well as cellular immune responses were also examined. We found that CLH001-immunized mice showed 100% survival against intranasal and aerosol challenge with B . mallei ATCC 23344. Moreover, this vaccine also afforded significant cross-protection against B . pseudomallei K96243, with low level bacterial burden detected in organs. Immunization with a prime and boost regimen of CLH001 induced significantly greater levels of total and subclasses of IgG, and generated antigen-specific splenocyte production of IFN-γ and IL-17A. Interestingly, protection induced by CLH001 is primarily dependent on humoral immunity, while CD4 + and CD8 + T cells played a less critical protective role. Conclusions/Significance Our data indicate that CLH001 serves as an effective live attenuated vaccine to prevent glanders and melioidosis. The quantity and quality of antibody responses as well as improving cell-mediated immune responses following vaccination need to be further investigated prior to advancement to preclinical studies.