A naturally derived outer-membrane vesicle vaccine protects against lethal pulmonary Burkholderia pseudomallei infection

被引:92
作者
Nieves, Wildaliz [1 ]
Asakrah, Saja [1 ]
Qazi, Omar [2 ]
Brown, Katherine A. [2 ,3 ]
Kurtz, Jonathan [1 ]
AuCoin, David P. [4 ]
McLachlan, James B. [1 ]
Roy, Chad J. [1 ,5 ]
Morici, Lisa A. [1 ]
机构
[1] Tulane Univ, Sch Med, Dept Microbiol & Immunol, New Orleans, LA 70112 USA
[2] Univ Texas Austin, Inst Cell & Mol Biol, Austin, TX 78712 USA
[3] Univ Texas Austin, Dept Chem & Biochem, Austin, TX 78712 USA
[4] Univ Nevada, Dept Microbiol, Sch Med, Reno, NV 89557 USA
[5] Tulane Natl Primate Res Ctr, Div Microbiol, Covington, LA USA
关键词
Aerosol; Intracellular; Persistence; OMV; MURINE MODEL; T-CELLS; CAPSULAR POLYSACCHARIDE; MONOCLONAL-ANTIBODIES; OMV VACCINE; NEW-ZEALAND; IN-VITRO; IMMUNITY; LIPOPOLYSACCHARIDE; MELIOIDOSIS;
D O I
10.1016/j.vaccine.2011.08.058
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Burkholderia pseudomallei, and other members of the Burkholderia, are among the most antibiotic-resistant bacterial species encountered in human infection. Mortality rates associated with severe B. pseudomallei infection approach 50% despite therapeutic treatment. A protective vaccine against B. pseudomallei would dramatically reduce morbidity and mortality in endemic areas and provide a safeguard for the U.S. and other countries against biological attack with this organism. In this study, we investigated the immunogenicity and protective efficacy of B. pseudomallei-derived outer membrane vesicles (OMVs). Vesicles are produced by Gram-negative and Gram-positive bacteria and contain many of the bacterial products recognized by the host immune system during infection. We demonstrate that subcutaneous (SC) immunization with OMVs provides significant protection against an otherwise lethal B. pseudomallei aerosol challenge in BALB/c mice. Mice immunized with B. pseudomallei OMVs displayed OMV-specific serum antibody and T-cell memory responses. Furthermore, OMV-mediated immunity appears species-specific as cross-reactive antibody and T cells were not generated in mice immunized with Escherichia coli-derived OMVs. These results provide the first compelling evidence that OMVs represent a non-living vaccine formulation that is able to produce protective humoral and cellular immunity against an aerosolized intracellular bacterium. This vaccine platform constitutes a safe and inexpensive immunization strategy against B. pseudomallei that can be exploited for other intracellular respiratory pathogens, including other Burkholderia and bacteria capable of establishing persistent infection. (C) 2011 Elsevier Ltd. All rights reserved.
引用
收藏
页码:8381 / 8389
页数:9
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