Effects of the insertion of a nonapeptide from murine IL-1β on the immunogenicity of carrier proteins delivered by live attenuated Salmonella

被引:3
作者
Chen, I
Pizza, M
Rappuoli, R
Newton, SMC
机构
[1] IRIS, Chiron Vaccines Immunobiol Res Inst, I-53100 Siena, Italy
[2] Univ Sao Paulo, Inst Ciencias Biomed, Dept Microbiol, BR-05508900 Sao Paulo, Brazil
关键词
IL-1 beta nonapeptide; Salmonella; adjuvant;
D O I
10.1007/s002030050550
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
A nonapeptide from IL-I beta has been reported to be an immunostimulant and adjuvant. To investigate the possibility of enhancing the immunogenicity of recombi nant antigens delivered by live-attenuated Salmonella strains, we inserted an oligonucleotide coding for the nonapeptide from murine IL-1 beta into the genes of three model proteins: LamB, MalE, and flagellin. The hybrid proteins were expressed and delivered in vivo by Salmonella aroA strains, and serum antibody responses were analyzed. The results showed that the nonapeptide induced an increase in the immune response against Salmonella-delivered flagellin, measured on day 28 post-immunization. However, the adjuvant effect was lost by day 42. In no case was an adjuvant effect detected for Salmonella-delivered LamB or MalE. Thus, by comparing the immune responses raised by purified MalE with and without the peptide, we investigated whether the insertion of the peptide affected the immunogenicity of the protein itself. Also in this case, a modest adjuvant effect was shown only after primary immunization and when very low doses of antigen were used. In conclusion, the immunomodulatory properties of the IL-1 beta peptide can also be detected when it is delivered in vivo by Salmonella; however, the effect is modest and antigen-dependent.
引用
收藏
页码:113 / 119
页数:7
相关论文
共 32 条
[1]  
ANTONI G, 1986, J IMMUNOL, V137, P3201
[2]  
BECKERS W, 1993, J IMMUNOL, V151, P1757
[3]   INVIVO STIMULATION AND RESTORATION OF THE IMMUNE-RESPONSE BY THE NONINFLAMMATORY FRAGMENT 163-171 OF HUMAN INTERLEUKIN-1-BETA [J].
BORASCHI, D ;
NENCIONI, L ;
VILLA, L ;
CENSINI, S ;
BOSSU, P ;
GHIARA, P ;
PRESENTINI, R ;
PERIN, F ;
FRASCA, D ;
DORIA, G ;
FORNI, G ;
MUSSO, T ;
GIOVARELLI, M ;
GHEZZI, P ;
BERTINI, R ;
BESEDOVSKY, HO ;
DELREY, A ;
SIPE, JD ;
ANTONI, G ;
SILVESTRI, S ;
TAGLIABUE, A .
JOURNAL OF EXPERIMENTAL MEDICINE, 1988, 168 (02) :675-686
[4]   MUTAGENESIS BY RANDOM LINKER INSERTION INTO THE LAMB GENE OF ESCHERICHIA-COLI-K12 [J].
BOULAIN, JC ;
CHARBIT, A ;
HOFNUNG, M .
MOLECULAR & GENERAL GENETICS, 1986, 205 (02) :339-348
[5]   PROBING THE TOPOLOGY OF A BACTERIAL-MEMBRANE PROTEIN BY GENETIC INSERTION OF A FOREIGN EPITOPE - EXPRESSION AT THE CELL-SURFACE [J].
CHARBIT, A ;
BOULAIN, JC ;
RYTER, A ;
HOFNUNG, M .
EMBO JOURNAL, 1986, 5 (11) :3029-3037
[6]   EXPRESSION AND IMMUNOGENICITY OF THE V3 LOOP FROM THE ENVELOPE OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 IN AN ATTENUATED AROA STRAIN OF SALMONELLA-TYPHIMURIUM UPON GENETIC COUPLING TO 2 ESCHERICHIA-COLI CARRIER PROTEINS [J].
CHARBIT, A ;
MARTINEAU, P ;
RONCO, J ;
LECLERC, C ;
LOMAN, R ;
MICHEL, V ;
OCALLAGHAN, D ;
HOFNUNG, M .
VACCINE, 1993, 11 (12) :1221-1228
[7]   CONSTRUCTION OF A GENETICALLY DEFINED SALMONELLA-TYPHI TY2 AROA, AROC MUTANT FOR THE ENGINEERING OF A CANDIDATE ORAL TYPHOID TETANUS VACCINE [J].
CHATFIELD, SN ;
FAIRWEATHER, N ;
CHARLES, I ;
PICKARD, D ;
LEVINE, M ;
HONE, D ;
POSADA, M ;
STRUGNELL, RA ;
DOUGAN, G .
VACCINE, 1992, 10 (01) :53-60
[8]   SILENT AND FUNCTIONAL-CHANGES IN THE PERIPLASMIC MALTOSE-BINDING PROTEIN OF ESCHERICHIA-COLI-K12 .1. TRANSPORT OF MALTOSE [J].
DUPLAY, P ;
SZMELCMAN, S ;
BEDOUELLE, H ;
HOFNUNG, M .
JOURNAL OF MOLECULAR BIOLOGY, 1987, 194 (04) :663-673
[9]   GENETIC-CONTROL OF ANTIBODY-RESPONSES INDUCED AGAINST AN ANTIGEN DELIVERED BY RECOMBINANT ATTENUATED SALMONELLA-TYPHIMURIUM [J].
FAYOLLE, C ;
OCALLAGHAN, D ;
MARTINEAU, P ;
CHARBIT, A ;
CLEMENT, JM ;
HOFNUNG, M ;
LECLERC, C .
INFECTION AND IMMUNITY, 1994, 62 (10) :4310-4319
[10]   SOLUBILIZATION OF CYTOPLASMIC MEMBRANE OF ESCHERICHIA-COLI BY IONIC DETERGENT SODIUM-LAURYL SARCOSINATE [J].
FILIP, C ;
FLETCHER, G ;
WULFF, JL ;
EARHART, CF .
JOURNAL OF BACTERIOLOGY, 1973, 115 (03) :717-722