SURFACE DISPLAY COMPARED TO PERIPLASMIC EXPRESSION OF A MALARIAL ANTIGEN IN SALMONELLA-TYPHIMURIUM AND ITS IMPLICATIONS FOR IMMUNOGENICITY

被引:41
作者
HADDAD, D
LILJEQVIST, S
KUMAR, S
HANSSON, M
STAHL, S
PERLMANN, H
PERLMANN, P
BERZINS, K
机构
[1] ROYAL INST TECHNOL,DEPT BIOCHEM,S-10044 STOCKHOLM,SWEDEN
[2] NATL INST HLTH,MALARIA RES LAB,BETHESDA,MD
来源
FEMS IMMUNOLOGY AND MEDICAL MICROBIOLOGY | 1995年 / 12卷 / 3-4期
关键词
SALMONELLA TYPHIMURIUM; STAPHYLOCOCCAL PROTEIN A; OUTER MEMBRANE PROTEIN A; PLASMODIUM FALCIPARUM; PFL; 55/RESA;
D O I
10.1016/0928-8244(95)00063-0
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Two different expression systems were investigated for the production of an 80 amino acid polypeptide, M3, from the C-terminus of the Plasmodium falciparum blood stage antigen Pf155/RESA in an attenuated Salmonella typhimurium vaccine strain, Upon expression, the malarial polypeptide was targeted either to the periplasm as a soluble fusion protein containing two IgG-binding domains (ZZ) from the staphylococcal protein A or, to the bacterial surface as an insert within a chimeric outer membrane protein A (OmpA) derived from Escherichia coli and Shigella dysenteriae. Both the ZZM3 and the OmpAM3 proteins were stably expressed in the periplasm or on the surface of Salmonella, respectively. The ZZ expression system yielded 10-100 times more malarial immunogen than did the OmpA system. Live recombinant Salmonella expressing ZZM3 or OmpAM3 were used to immunize mice intraperitoneally. Both the ZZM3 and OmpAM3 genes persisted for up to three weeks in bacteria isolated from different lymphoid organs. Bacteria expressing ZZM3 induced antibodies to M3, ZZ and to the Pf155/RESA antigen whereas, bacteria producing OmpAM3 induced similar levels of antibodies reactive with M3 but not with Pf155/RESA, Both recombinants induced a memory response of antibodies reactive with both M3 and Pf155/RESA, The high levels of M3 produced by the ZZ expression system make it suitable for the expression of heterologous antigens in Salmonella. Nevertheless, in spite of the quantitative difference in M3 expression, the ZZ and OmpA constructs elicited comparable immune responses to M3.
引用
收藏
页码:175 / 185
页数:11
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