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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.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.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.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.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