Tags

Type your tag names separated by a space and hit enter

Evaluation of Burkholderia mallei ΔtonB Δhcp1 (CLH001) as a live attenuated vaccine in murine models of glanders and melioidosis.
PLoS Negl Trop Dis. 2019 07; 13(7):e0007578.PN

Abstract

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 ΔtonB Δhcp1 (CLH001) live-attenuated vaccine demonstrated that it is attenuated, safe and protective against B. mallei wild-type strains 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.

Authors+Show Affiliations

Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, United States of America.Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, United States of America.Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, United States of America.Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, United States of America.Department of Pathology, University of Texas Medical Branch, Galveston, Texas, United States of America.Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, United States of America.Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, United States of America. Department of Pathology, University of Texas Medical Branch, Galveston, Texas, United States of America.

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

31306423

Citation

Khakhum, Nittaya, et al. "Evaluation of Burkholderia Mallei ΔtonB Δhcp1 (CLH001) as a Live Attenuated Vaccine in Murine Models of Glanders and Melioidosis." PLoS Neglected Tropical Diseases, vol. 13, no. 7, 2019, pp. e0007578.
Khakhum N, Bharaj P, Myers JN, et al. Evaluation of Burkholderia mallei ΔtonB Δhcp1 (CLH001) as a live attenuated vaccine in murine models of glanders and melioidosis. PLoS Negl Trop Dis. 2019;13(7):e0007578.
Khakhum, N., Bharaj, P., Myers, J. N., Tapia, D., Walker, D. H., Endsley, J. J., & Torres, A. G. (2019). Evaluation of Burkholderia mallei ΔtonB Δhcp1 (CLH001) as a live attenuated vaccine in murine models of glanders and melioidosis. PLoS Neglected Tropical Diseases, 13(7), e0007578. https://doi.org/10.1371/journal.pntd.0007578
Khakhum N, et al. Evaluation of Burkholderia Mallei ΔtonB Δhcp1 (CLH001) as a Live Attenuated Vaccine in Murine Models of Glanders and Melioidosis. PLoS Negl Trop Dis. 2019;13(7):e0007578. PubMed PMID: 31306423.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Evaluation of Burkholderia mallei ΔtonB Δhcp1 (CLH001) as a live attenuated vaccine in murine models of glanders and melioidosis. AU - Khakhum,Nittaya, AU - Bharaj,Preeti, AU - Myers,Julia N, AU - Tapia,Daniel, AU - Walker,David H, AU - Endsley,Janice J, AU - Torres,Alfredo G, Y1 - 2019/07/15/ PY - 2019/03/07/received PY - 2019/06/25/accepted PY - 2019/07/25/revised PY - 2019/7/16/pubmed PY - 2020/1/7/medline PY - 2019/7/16/entrez SP - e0007578 EP - e0007578 JF - PLoS neglected tropical diseases JO - PLoS Negl Trop Dis VL - 13 IS - 7 N2 - 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 ΔtonB Δhcp1 (CLH001) live-attenuated vaccine demonstrated that it is attenuated, safe and protective against B. mallei wild-type strains 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. SN - 1935-2735 UR - https://www.unboundmedicine.com/medline/citation/31306423/Evaluation_of_Burkholderia_mallei_ΔtonB_Δhcp1__CLH001__as_a_live_attenuated_vaccine_in_murine_models_of_glanders_and_melioidosis_ L2 - https://dx.plos.org/10.1371/journal.pntd.0007578 DB - PRIME DP - Unbound Medicine ER -