Increases of efficacy as vaccine against Brucella abortus infection in mice by simultaneous inoculation with avirulent smooth bvrS/bvrR and rough wbkA mutants

被引:40
作者
Grilló, MJ
Manterola, L
de Miguel, MJ
Muñoz, PM
Blasco, JM
Moriyón, I
López-Goñi, I
机构
[1] CITA, Zaragoza 50080, Spain
[2] Univ Navarra, Dept Microbiol & Parasitol, E-31080 Pamplona, Spain
关键词
Brucella; vaccines; bvrS/bvrR-wbkA mutants;
D O I
10.1016/j.vaccine.2005.12.038
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 Brucella abortus S19 and RB51 strains are the most widely used live vaccines against bovine brucellosis. However, both can induce abortion and milk excretion, S19 vaccination interferes in serological tests, and RB51 is less effective. We have shown previously that a rough wbkA B. abortus mutant is attenuated and a better vaccine than RB51 in BALB/c mice, and that mutants in the two-component regulatory system bvrS/bvrR are markedly attenuated while keeping a smooth lipopolysaccharide (S-LPS). In this work, we tested whether simultaneous inoculation with live bvrS increases wbkA vaccine efficacy in mice. Even at high doses, the bvrS mutant was cleared much faster from spleens than the wbkA mutant. The splenic persistence of the wbkA mutant increased when inoculated along with the bvrS mutant, but also with inactivated bvrS cells or with purified B. abortus S-LPS, strongly suggesting that S-LPS in the bvrS mutant played a determinant role in the wbkA persistence. When inoculated alone, both mutants, protected against virulent B. abortus but less than when inoculated simultaneously, and the protection afforded by the combination was better than that obtained with B. abortus S19. Increased protection was also obtained after simultaneous inoculation of the wbkA mutant and inactivated bwrS cells or purified S-LPS, showing again the role played by the S-LPS in the bvrS cells. In mice, the bvrS-whkA combination induced an antibody response reduced with respect to B. abortus S 19 vaccination. Thus, the simultaneous use of live bvrS and wbkA B. abortus mutants seems a promising approach to overcome the problems of the S 19 and RB51 vaccines. (c) 2005 Elsevier Ltd. All rights reserved.
引用
收藏
页码:2910 / 2916
页数:7
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