Outer membrane vesicles as an acellular vaccine against Acinetobacter baumannii

被引:192
作者
McConnell, Michael J. [1 ]
Rumbo, Carlos [2 ]
Bou, German [2 ]
Pachon, Jeronimo [1 ]
机构
[1] Univ Seville, Inst Biomed Sevilla, Unit Infect Dis Microbiol & Prevent Med, Hosp Univ Virgen del Rocio,CSIC, Seville 41013, Spain
[2] Complexo Hosp Univ A Coruna, Serv Microbioloxia INIBIC, La Coruna 15006, Spain
关键词
Acinetobacter baumannii; Outer membrane vesicles; Vaccine; MULTIDRUG-RESISTANT ACINETOBACTER; PROTECTIVE IMMUNITY; MICE; IMMUNIZATION; BACTEREMIA; PATHOGEN; IMPACT;
D O I
10.1016/j.vaccine.2011.06.001
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Acinetobacter baumannii produces different types of infections including pneumonia, meningitis, and bloodstream infections. The optimal treatment of these infections has been complicated by the global emergence of multidrug resistant strains, requiring the development of novel approaches for treatment and prevention. Outer membrane vesicles are outpouchings of the bacterial outer membrane that are secreted from numerous pathogenic Gram-negative bacteria. In the present study, we describe the isolation of outer membrane vesicles from A. baumannii and their use as a vaccine in a mouse model of disseminated sepsis. Immunization produced a robust antibody response against multiple bacterial antigens which consisted of antigen-specific IgG and IgM. In addition, both IgG1 and IgG2c subtypes were produced by immunization. Immunized mice had lower tissue bacterial loads and lower serum levels of the pro-inflammatory cytokines IL-6 and IL-1 beta post-infection compared to control mice. Importantly, vaccination protected mice from challenge with the ATCC 19606 strain and provided protection against two clinical isolates, including a pan-resistant strain. These results indicate that vaccination with outer membrane vesicles may be a viable strategy for preventing A. baumannii infection. (C) 2011 Elsevier Ltd. All rights reserved.
引用
收藏
页码:5705 / 5710
页数:6
相关论文
共 23 条
[1]   Long-Distance Delivery of Bacterial Virulence Factors by Pseudomonas aeruginosa Outer Membrane Vesicles [J].
Bomberger, Jennifer M. ;
MacEachran, Daniel P. ;
Coutermarsh, Bonita A. ;
Ye, Siying ;
O'Toole, George A. ;
Stanton, Bruce A. .
PLOS PATHOGENS, 2009, 5 (04)
[2]   Bacteremia due to Acinetobacter baumannii epidemiology, clinical findings, and prognostic features [J].
Cisneros, JM ;
Reyes, MJ ;
Pachon, J ;
Becerril, B ;
Caballero, FJ ;
GarciaGarmendia, JL ;
Ortiz, C ;
Cobacho, AR .
CLINICAL INFECTIOUS DISEASES, 1996, 22 (06) :1026-1032
[3]   Mortality and the increase in length of stay attributable to the acquisition of Acinetobacter in critically ill patients [J].
García-Garmendia, JL ;
Ortiz-Leyba, C ;
Garnacho-Montero, J ;
Jiménez-Jiménez, FJ ;
Monterrubio-Villar, J ;
Gili-Miner, M .
CRITICAL CARE MEDICINE, 1999, 27 (09) :1794-1799
[4]   Clinical impact of pneumonia caused by Acinetobacter baumannii in intubated patients:: A matched cohort study [J].
Garnacho, J ;
Sole-Violan, J ;
Sa-Borges, M ;
Diaz, E ;
Rello, J .
CRITICAL CARE MEDICINE, 2003, 31 (10) :2478-2482
[5]   Antibiotic Resistance in Community-Acquired Pneumonia Caused by Streptococcus pneumoniae, Methicillin-Resistant Staphylococcus aureus, and Acinetobacter baumannii [J].
Ho, Pak-Leung ;
Cheng, Vincent Chi-Chung ;
Chu, Chung-Ming .
CHEST, 2009, 136 (04) :1119-1127
[6]   Importation of multidrug-resistant Acinetobacter spp infections with casualties from Iraq [J].
Jones, Anna ;
Morgan, Dilys ;
Walsh, Amanda ;
Turton, Jane ;
Livermore, David ;
Pitt, Tyrone ;
Green, Andy ;
Gill, Martin ;
Mortiboy, Deborah .
LANCET INFECTIOUS DISEASES, 2006, 6 (06) :317-318
[7]   Differences in immunogenicity and protection in mice and guinea pigs following intranasal immunization with Helicobacter pylori outer membrane antigens [J].
Keenan, JI ;
Rijpkema, SG ;
Durrani, Z ;
Roake, JA .
FEMS IMMUNOLOGY AND MEDICAL MICROBIOLOGY, 2003, 36 (03) :199-205
[8]   Bactericidal antibody responses elicited by a meningococcal outer membrane vesicle vaccine with overexpressed factor H-binding protein and genetically attenuated endotoxin [J].
Koeberling, Oliver ;
Seubert, Anja ;
Granoff, Dan M. .
JOURNAL OF INFECTIOUS DISEASES, 2008, 198 (02) :262-270
[9]   Bacterial outer membrane vesicles and the host-pathogen interaction [J].
Kuehn, MJ ;
Kesty, NC .
GENES & DEVELOPMENT, 2005, 19 (22) :2645-2655
[10]  
KULP A, 2010, ANN REV MICROBIO OCT, P163