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Characterization of the Burkholderia mallei tonB Mutant and Its Potential as a Backbone Strain for Vaccine Development.

Mott TM, Vijayakumar S, Sbrana E, Endsley JJ, Torres AG - PLoS Negl Trop Dis (2015)

Bottom Line: At 21 days post-immunization, TMM001-treated animals showed significantly higher levels of B. mallei-specific IgG1, IgG2a and IgM when compared to PBS-treated controls.In a cross-protection study of acute inhalational melioidosis with B. pseudomallei, TMM001-treated mice were significantly protected.Although further work is needed to prevent chronic infection by TMM001 while maintaining immunogenicity, our attenuated strain demonstrates great potential as a backbone strain for future vaccine development against both glanders and melioidosis.

View Article: PubMed Central - PubMed

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

ABSTRACT

Background: In this study, a Burkholderia mallei tonB mutant (TMM001) deficient in iron acquisition was constructed, characterized, and evaluated for its protective properties in acute inhalational infection models of murine glanders and melioidosis.

Methodology/principal findings: Compared to the wild-type, TMM001 exhibits slower growth kinetics, siderophore hyper-secretion and the inability to utilize heme-containing proteins as iron sources. A series of animal challenge studies showed an inverse correlation between the percentage of survival in BALB/c mice and iron-dependent TMM001 growth. Upon evaluation of TMM001 as a potential protective strain against infection, we found 100% survival following B. mallei CSM001 challenge of mice previously receiving 1.5 x 10(4) CFU of TMM001. At 21 days post-immunization, TMM001-treated animals showed significantly higher levels of B. mallei-specific IgG1, IgG2a and IgM when compared to PBS-treated controls. At 48 h post-challenge, PBS-treated controls exhibited higher levels of serum inflammatory cytokines and more severe pathological damage to target organs compared to animals receiving TMM001. In a cross-protection study of acute inhalational melioidosis with B. pseudomallei, TMM001-treated mice were significantly protected. While wild type was cleared in all B. mallei challenge studies, mice failed to clear TMM001.

Conclusions/significance: Although further work is needed to prevent chronic infection by TMM001 while maintaining immunogenicity, our attenuated strain demonstrates great potential as a backbone strain for future vaccine development against both glanders and melioidosis.

No MeSH data available.


Related in: MedlinePlus

B. mallei-specific immunoglobulin levels in TMM001- vs PBS-treated mice before challenge.Murine serum samples were taken 21 days post-immunization, diluted 1:10,000 and analyzed for B. mallei-specific IgG1 (A), IgG2a (B) and IgM (C). Mean ± SEM of three representative animals is plotted. Statistical significance was determined by the unpaired t test with equal SD. ★ p ≤ 0.05 ★★★ p ≤ 0.001, ★★★★ p ≤ 0.0001.
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pntd.0003863.g005: B. mallei-specific immunoglobulin levels in TMM001- vs PBS-treated mice before challenge.Murine serum samples were taken 21 days post-immunization, diluted 1:10,000 and analyzed for B. mallei-specific IgG1 (A), IgG2a (B) and IgM (C). Mean ± SEM of three representative animals is plotted. Statistical significance was determined by the unpaired t test with equal SD. ★ p ≤ 0.05 ★★★ p ≤ 0.001, ★★★★ p ≤ 0.0001.

Mentions: The generation of murine humoral immune responses to B. mallei following treatment with mock (PBS) or TMM001 was determined by analysis of sera using ELISA. Compared to mock-vaccinated mice, sera from TMM001-treated mice had significantly higher titers of B. mallei-specific IgM and IgG antibodies (Fig 5). Mean differences in absorbance for IgG1, IgG2a, and IgM were 5.4-fold (p = 0.0009), 4.8-fold (p = 0.0106), and 10.9-fold (p = 0.0028) higher, respectively, in TMM001-vaccinated mice.


Characterization of the Burkholderia mallei tonB Mutant and Its Potential as a Backbone Strain for Vaccine Development.

Mott TM, Vijayakumar S, Sbrana E, Endsley JJ, Torres AG - PLoS Negl Trop Dis (2015)

B. mallei-specific immunoglobulin levels in TMM001- vs PBS-treated mice before challenge.Murine serum samples were taken 21 days post-immunization, diluted 1:10,000 and analyzed for B. mallei-specific IgG1 (A), IgG2a (B) and IgM (C). Mean ± SEM of three representative animals is plotted. Statistical significance was determined by the unpaired t test with equal SD. ★ p ≤ 0.05 ★★★ p ≤ 0.001, ★★★★ p ≤ 0.0001.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4482651&req=5

pntd.0003863.g005: B. mallei-specific immunoglobulin levels in TMM001- vs PBS-treated mice before challenge.Murine serum samples were taken 21 days post-immunization, diluted 1:10,000 and analyzed for B. mallei-specific IgG1 (A), IgG2a (B) and IgM (C). Mean ± SEM of three representative animals is plotted. Statistical significance was determined by the unpaired t test with equal SD. ★ p ≤ 0.05 ★★★ p ≤ 0.001, ★★★★ p ≤ 0.0001.
Mentions: The generation of murine humoral immune responses to B. mallei following treatment with mock (PBS) or TMM001 was determined by analysis of sera using ELISA. Compared to mock-vaccinated mice, sera from TMM001-treated mice had significantly higher titers of B. mallei-specific IgM and IgG antibodies (Fig 5). Mean differences in absorbance for IgG1, IgG2a, and IgM were 5.4-fold (p = 0.0009), 4.8-fold (p = 0.0106), and 10.9-fold (p = 0.0028) higher, respectively, in TMM001-vaccinated mice.

Bottom Line: At 21 days post-immunization, TMM001-treated animals showed significantly higher levels of B. mallei-specific IgG1, IgG2a and IgM when compared to PBS-treated controls.In a cross-protection study of acute inhalational melioidosis with B. pseudomallei, TMM001-treated mice were significantly protected.Although further work is needed to prevent chronic infection by TMM001 while maintaining immunogenicity, our attenuated strain demonstrates great potential as a backbone strain for future vaccine development against both glanders and melioidosis.

View Article: PubMed Central - PubMed

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

ABSTRACT

Background: In this study, a Burkholderia mallei tonB mutant (TMM001) deficient in iron acquisition was constructed, characterized, and evaluated for its protective properties in acute inhalational infection models of murine glanders and melioidosis.

Methodology/principal findings: Compared to the wild-type, TMM001 exhibits slower growth kinetics, siderophore hyper-secretion and the inability to utilize heme-containing proteins as iron sources. A series of animal challenge studies showed an inverse correlation between the percentage of survival in BALB/c mice and iron-dependent TMM001 growth. Upon evaluation of TMM001 as a potential protective strain against infection, we found 100% survival following B. mallei CSM001 challenge of mice previously receiving 1.5 x 10(4) CFU of TMM001. At 21 days post-immunization, TMM001-treated animals showed significantly higher levels of B. mallei-specific IgG1, IgG2a and IgM when compared to PBS-treated controls. At 48 h post-challenge, PBS-treated controls exhibited higher levels of serum inflammatory cytokines and more severe pathological damage to target organs compared to animals receiving TMM001. In a cross-protection study of acute inhalational melioidosis with B. pseudomallei, TMM001-treated mice were significantly protected. While wild type was cleared in all B. mallei challenge studies, mice failed to clear TMM001.

Conclusions/significance: Although further work is needed to prevent chronic infection by TMM001 while maintaining immunogenicity, our attenuated strain demonstrates great potential as a backbone strain for future vaccine development against both glanders and melioidosis.

No MeSH data available.


Related in: MedlinePlus