Monoclonal Antibodies Passively Protect BALB/c Mice against
            <i>Burkholderia mallei</i>
            Aerosol Challenge

Treviño, Sylvia R.; Permenter, Amy R.; England, Marilyn J.; Parthasarathy, Narayanan; Gibbs, Paul; Waag, David M.; Chanh, Tran C.

doi:10.1128/iai.74.3.1958-1961.2006

Cited by 35 publications

(35 citation statements)

References 11 publications

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“…In other studies protection in mice can be achieved with monoclonal antibodies against B. mallei administered prior to, but not after, challenge. 21 However, in these studies the animals' spleens were heavily colonized with B. mallei despite surviving the infection 21 and a similar result was observed with a lipoprotein vaccination of B. pseudomallei. 18 This current work presents data and identifies potential immunogenic antigens that may be exploited to develop new protective antibodies that overcome this limitation.…”

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confidence: 63%

Distinct human antibody response to the biological warfare agentBurkholderia mallei

et al. 2012

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confidence: 63%

Distinct human antibody response to the biological warfare agentBurkholderia mallei

et al. 2012

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“…Passive transfer of immune serum (elicited by vaccination with Bp82) to BALB/c mice resulted in ϳ40% survival rates during the acute and chronic stages of infection, and vaccination of mice lacking B cells with the attenuated strain did not protect against subsequent lethal intranasal challenge with WT organisms. Passive transfer of immune serum elicited by vaccination with B. pseudomallei 1026b outer membrane vesicles was shown to provide 80% survival against intraperitoneal challenge of BALB/c mice with a lethal dose of B. pseudomallei K96243 (135), and monoclonal antibodies targeting LPS passively protected BALB/c mice against aerosol infection with 20 LD 50 of B. mallei ATCC 23344 (up to 100% survival) by reducing bacterial numbers below the lethal threshold (138). Hyperimmune sera from horses vaccinated with mallein extract have also been successfully used to treat human patients with glanders (139-141).…”

Section: Discussionmentioning

confidence: 99%

Antibodies against In Vivo -Expressed Antigens Are Sufficient To Protect against Lethal Aerosol Infection with Burkholderia mallei and Burkholderia pseudomallei

et al. 2017

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Burkholderia mallei, a facultative intracellular bacterium and tier 1 biothreat, causes the fatal zoonotic disease glanders. The organism possesses multiple genes encoding autotransporter proteins, which represent important virulence factors and targets for developing countermeasures in pathogenic Gram-negative bacteria. In the present study, we investigated one of these autotransporters, BatA, and demonstrate that it displays lipolytic activity, aids in intracellular survival, is expressed in vivo, elicits production of antibodies during infection, and contributes to pathogenicity in a mouse aerosol challenge model. A mutation in the batA gene of wild-type strain ATCC 23344 was found to be particularly attenuating, as BALB/c mice infected with the equivalent of 80 median lethal doses cleared the organism. This finding prompted us to test the hypothesis that vaccination with the batA mutant strain elicits protective immunity against subsequent infection with wild-type bacteria. We discovered that not only does vaccination provide high levels of protection against lethal aerosol challenge with B. mallei ATCC 23344, it also protects against infection with multiple isolates of the closely related organism and causative agent of melioidosis, Burkholderia pseudomallei. Passive-transfer experiments also revealed that the protective immunity afforded by vaccination with the batA mutant strain is predominantly mediated by IgG antibodies binding to antigens expressed exclusively in vivo. Collectively, our data demonstrate that BatA is a target for developing medical countermeasures and that vaccination with a mutant lacking expression of the protein provides a platform to gain insights regarding mechanisms of protective immunity against B. mallei and B. pseudomallei, including antigen discovery.

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“…A serum-free protein block plus 5% normal goat serum was applied for 30 min. A monoclonal mouse antibody (3B3-5) to lipopolysaccharide (LPS) of B. pseudomallei (D. Waag, USAMRIID; prepared as previously described for B. mallei [36]) was diluted 1:1,200 and incubated at room temperature for 60 min. A polymer-labeled horseradish peroxidase anti-rabbit secondary antibody (EnVision Plus System; Dako Corp., Carpinteria, CA) was applied for 30 min at room temperature.…”

Section: Methodsmentioning

confidence: 99%

Natural History of Inhalation Melioidosis in Rhesus Macaques (Macaca mulatta) and African Green Monkeys (Chlorocebus aethiops)

et al. 2012

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ABSTRACTBurkholderia pseudomallei, the causative agent of melioidosis, is recognized as a serious health threat due to its involvement in septic and pulmonary infections in areas of endemicity and is recognized by the Centers for Disease Control and Prevention as a category B biothreat agent. An animal model is desirable to evaluate the pathogenesis of melioidosis and medical countermeasures. A model system that represents human melioidosis infections is essential in this process. A group of 10 rhesus macaques (RMs) and 10 African green monkeys (AGMs) was exposed to aerosolizedB. pseudomallei1026b. The first clinical signs were fever developing 24 to 40 h postexposure followed by leukocytosis resulting from a high percentage of neutrophils. Dyspnea manifested 2 to 4 days postexposure. In the AGMs, an increase in interleukin 1β (IL-1β), IL-6, IL-8, gamma interferon (IFN-γ), and tumor necrosis factor alpha (TNF-α) was observed. In the RMs, IL-1β, IL-6, and TNF-α increased. All the RMs and AGMs had various degrees of bronchopneumonia, with inflammation consisting of numerous neutrophils and a moderate number of macrophages. Both the RMs and the AGMs appear to develop a melioidosis infection that closely resembles that seen in acute human melioidosis. However, for an evaluation of medical countermeasures, AGMs appear to be a more appropriate model.

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Monoclonal Antibodies Passively Protect BALB/c Mice against Burkholderia mallei Aerosol Challenge

Cited by 35 publications

References 11 publications

Distinct human antibody response to the biological warfare agentBurkholderia mallei

Distinct human antibody response to the biological warfare agentBurkholderia mallei

Antibodies against In Vivo -Expressed Antigens Are Sufficient To Protect against Lethal Aerosol Infection with Burkholderia mallei and Burkholderia pseudomallei

Natural History of Inhalation Melioidosis in Rhesus Macaques (Macaca mulatta) and African Green Monkeys (Chlorocebus aethiops)

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