Immunization with Vibrio cholerae outer membrane vesicles induces protective immunity in mice

被引:152
作者
Schild, Stefan [1 ,2 ,3 ]
Nelson, Eric J. [1 ,2 ]
Camilli, Andrew [1 ,2 ]
机构
[1] Tufts Univ, Sch Med, Dept Mol Biol & Microbiol, Boston, MA 02111 USA
[2] Howard Hughes Med Inst, Boston, MA 02111 USA
[3] Karl Franzens Univ Graz, Inst Mol Biowissensch, A-8010 Graz, Austria
关键词
D O I
10.1128/IAI.00532-08
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The gram-negative bacterium Vibrio cholerae releases outer membrane vesicles (OMVs) during growth. In this study, we immunized female mice by the intranasal, intragastric, or intraperitoneal route with purified OMVs derived from V. cholerae. Independent of the route of immunization, mice induced specific, high-titer immune responses of similar levels against a variety of antigens present in the OMVs. After the last immunization, the half-maximum total immunoglobulin titer was stable over a 3-month period, indicating that the immune response was long lasting. The induction of specific isotypes, however, was dependent on the immunization route. Immunoglobulin A, for example, was induced to a significant level only by mucosal immunization, with the intranasal route generating the highest titers. We challenged the offspring of immunized female mice with V. cholerae via the oral route in two consecutive periods, approximately 30 and 95 days after the last immunization. Regardless of the route of immunization, the offspring was protected against colonization with V. cholerae in both challenge periods. Our results show that mucosal immunizations via both routes with OMVs derived from V. cholerae induce long-term protective immune responses against this gastrointestinal pathogen. These findings may contribute to the development of "nonliving," OMV-based vaccines against V. cholerae and other enteric pathogens, using the oral or intranasal route of immunization.
引用
收藏
页码:4554 / 4563
页数:10
相关论文
共 103 条
[11]   Enteric immunization: Promises and challenges [J].
Brown, WR .
DIGESTIVE DISEASES, 1996, 14 (03) :192-200
[12]   Cholera stool bacteria repress chemotaxis to increase infectivity [J].
Butler, SM ;
Nelson, EJ ;
Chowdhury, N ;
Faruque, SM ;
Calderwood, SB ;
Camilli, A .
MOLECULAR MICROBIOLOGY, 2006, 60 (02) :417-426
[13]   Both chemotaxis and net motility greatly influence the infectivity of Vibrio cholerae [J].
Butler, SM ;
Camilli, A .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (14) :5018-5023
[14]   Development of a germfree mouse model of Vibrio cholerae infection [J].
Butterton, JR ;
Ryan, ET ;
Shahin, RA ;
Calderwood, SB .
INFECTION AND IMMUNITY, 1996, 64 (10) :4373-4377
[15]  
CABRERA O, 2006, VACCINE S2, V24
[16]   RESPONSE OF MAN TO INFECTION WITH VIBRIO-CHOLERAE .1. CLINICAL, SEROLOGIC, AND BACTERIOLOGIC RESPONSES TO A KNOWN INOCULUM [J].
CASH, RA ;
MUSIC, SI ;
LIBONATI, JP ;
SNYDER, MJ ;
WENZEL, RP ;
HORNICK, RB .
JOURNAL OF INFECTIOUS DISEASES, 1974, 129 (01) :45-52
[17]   MECHANISM OF CHOLERA TOXIN ACTION - COVALENT MODIFICATION OF GUANYL NUCLEOTIDE-BINDING PROTEIN OF ADENYLATE-CYCLASE SYSTEM [J].
CASSEL, D ;
PFEUFFER, T .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1978, 75 (06) :2669-2673
[18]  
CHATTERJ.SN, 1967, J GEN MICROBIOL, V49, P1
[19]   rfb mutations in Vibrio cholerae do not affect surface production of toxin-coregulated pili but still inhibit intestinal colonization [J].
Chiang, SL ;
Mekalanos, JJ .
INFECTION AND IMMUNITY, 1999, 67 (02) :976-980
[20]   BREAST-FEEDING AND THE RISK OF SEVERE CHOLERA IN RURAL BANGLADESHI CHILDREN [J].
CLEMENS, JD ;
SACK, DA ;
HARRIS, JR ;
KHAN, MR ;
CHAKRABORTY, J ;
CHOWDHURY, S ;
RAO, MR ;
VANLOON, FPL ;
STANTON, BF ;
YUNUS, M ;
ALI, M ;
ANSARUZZAMAN, M ;
SVENNERHOLM, AM ;
HOLMGREN, J .
AMERICAN JOURNAL OF EPIDEMIOLOGY, 1990, 131 (03) :400-411