A recombinant subunit vaccine based on the insertion of 27 amino acids from Omp31 to the N-terminus of BLS induced a similar degree of protection against B-ovis than Rev.1 vaccination

被引:63
作者
Cassataro, Juliana
Pasquevich, Karina A.
Estein, Silvia M.
Laplagne, Diego A.
Velikovsky, Carlos A.
de la Barrera, Silvia
Bowden, Raul
Fossati, Carlos A.
Giambartolomei, Guillermo H.
Goldbaum, Fernando A.
机构
[1] UBA, Fac Med, Hosp Clin Jose San Martin, Immunogenet Lab, RA-1120 Buenos Aires, DF, Argentina
[2] UBA, Fac Farm & Bioquim, CONICET, IDEHU, Buenos Aires, DF, Argentina
[3] Univ Nacl, Ctr Provincia Buenos Aires, Fac Ciencias Vet,Lab Inmunol, Dept Sanidad Anim & Med Prevent, Tandil, Argentina
[4] Consejo Nacl Invest Cient & Tecn, Inst Leloir, Buenos Aires, DF, Argentina
[5] Acad Nacl Med Buenos Aires, Inst Invest Hematol, Dept Inmunol, Buenos Aires, DF, Argentina
关键词
Brucella spp; vaccine; virus-like particule; outer membrane protein; recombinant protein; lumazine synthase;
D O I
10.1016/j.vaccine.2007.03.028
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 development of an effective subunit vaccine against brucellosis is a research area of intense interest. The enzyme lumazine synthase from Brucella spp. (BLS) is highly immunogenic, presumably due to its decameric arrangement and remarkable stability. In this work we decided to develop a chimera with the scaffold protein BLS decorated with 10 copies of a known protective epitope derived from an outer membrane protein of 31 kDa (Omp31) from Brucella spp. Vaccination of BALB/c mice with the chimera as a recombinant protein (rBLSOmp31) provided the best protection level against Brucella ovis, which was higher than the given by the co-delivery of both recombinant proteins (rBLS + rOmp3 1) and similar than the control vaccine Brucella melitensis strain Rev.1. Moreover rBLSOmp31 induced protection against Brucella melitensis but to a lesser degree than Rev. I. The chimera induced a strong Immoral response against the inserted peptide. It also induced peptide- and BLS-specific T helper I and cytotoxic T responses. In conclusion, our results indicate that BLSOmp31 could be a useful candidate for the development of subunit vaccines against brucellosis since it elicits humoral, T helper and cytotoxic immune responses and protection against smooth and rough species of Brucella. (C) 2007 Elsevier Ltd. All rights reserved.
引用
收藏
页码:4437 / 4446
页数:10
相关论文
共 39 条
[1]   Protection of BALB/c mice against Brucella abortus 544 challenge by vaccination with bacterioferritin or P39 recombinant proteins with CpG oligodeoxynucleotides as adjuvant [J].
Al-Mariri, A ;
Tibor, A ;
Mertens, P ;
De Bolle, X ;
Michel, P ;
Godefroid, J ;
Walravens, K ;
Letesson, JJ .
INFECTION AND IMMUNITY, 2001, 69 (08) :4816-4822
[2]  
Alton G. G., 1985, Brucella melitensis. CEC seminar, Brussels, November 1984, P215
[3]   The influence of virus structure on antibody responses and virus serotype formation [J].
Bachmann, MF ;
Zinkernagel, RM .
IMMUNOLOGY TODAY, 1996, 17 (12) :553-558
[4]  
BERGUER PM, 2006, J IMMUNOL, V176
[5]   BRUCELLA-MELITENSIS REV-1 VACCINE AS A CAUSE OF HUMAN BRUCELLOSIS [J].
BLASCO, JM ;
DIAZ, R .
LANCET, 1993, 342 (8874) :805-805
[6]  
BLASCO JM, 1990, BRUCELLA OVIS ANIMAL, P352
[7]   OUTER-MEMBRANE PROTEIN-SPECIFIC AND ROUGH LIPOPOLYSACCHARIDE-SPECIFIC MONOCLONAL-ANTIBODIES PROTECT MICE AGAINST BRUCELLA-OVIS [J].
BOWDEN, RA ;
CLOECKAERT, A ;
ZYGMUNT, MS ;
DUBRAY, G .
JOURNAL OF MEDICAL MICROBIOLOGY, 1995, 43 (05) :344-347
[8]   Identification of protective outer membrane antigens of Brucella ovis by passive immunization of mice with monoclonal antibodies [J].
Bowden, RA ;
Estein, SM ;
Zygmunt, MS ;
Dubray, G ;
Cloeckaert, A .
MICROBES AND INFECTION, 2000, 2 (05) :481-488
[9]   Divergence in macromolecular assembly:: X-ray crystallographic structure analysis of lumazine synthase from Brucella abortus [J].
Braden, BC ;
Velikovsky, CA ;
Cauerhff, AA ;
Polikarpov, I ;
Goldbaum, FA .
JOURNAL OF MOLECULAR BIOLOGY, 2000, 297 (05) :1031-1036
[10]   EPIDIDYMITIS IN RAMS AND LAMBS [J].
BULGIN, MS .
VETERINARY CLINICS OF NORTH AMERICA-FOOD ANIMAL PRACTICE, 1990, 6 (03) :683-690