Immune responses dependent on antigen location in recombinant attenuated Salmonella typhimurium vaccines following oral immunization

Immune responses dependent on antigen location in recombinant attenuated Salmonella typhimurium vaccines following oral immunization
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DOI:
10.1016/s0928-8244(03)00063-4
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发表时间:
2003-07-15
影响因子:
--
通讯作者:
Curtiss, R
Curtiss, R
中科院分区:
其他
文献类型:
--
作者:
Kang, HY;Curtiss, R

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重组减毒沙门氏菌疫苗中重组抗原的亚细胞位置可能影响免疫原性,这取决于重组抗原暴露于参与全身免疫反应的细胞。有研究表明,分泌pYA3494指定的重组肺炎链球菌PspA (rPspA)抗原的重组减毒沙门氏菌疫苗可诱导保护性抗rPspA特异性免疫应答(Kang et al. (2002) infection。免疫学,1739-1749)。重组质粒pYA3496指定His(6)标记的rPspA (His(6)-rPspA)蛋白(无明显信号序列),使rPspA抗原定位到沙门氏菌的细胞质中。携带pYA3494或pYA3496的沙门氏菌疫苗表达了相似数量的rPspA。携带pYA3494或pYA3496重组沙门氏菌疫苗的10(9)个菌落形成单位(CFU)单次口服免疫BALB/c小鼠后,rPspA和沙门氏菌脂多糖(LPS)抗原均产生IgG抗体反应。携带pYA3494的沙门氏菌诱导的抗rpspa IgG滴度(1.9 × 10(7))比携带pYA3496的沙门氏菌诱导的(< 2.4 × 10(3))高10(4)倍。(C) 2003欧洲微生物学会联合会。Elsevier Science B.V.版权所有。
The subcellular location of a recombinant antigen in recombinant attenuated Salmonella vaccines may influence immunogenicity dependent on exposure of the recombinant antigen to cells involved in systemic immune responses. It has been shown that a recombinant attenuated Salmonella vaccine secreting the recombinant Streptococcus pneumoniae PspA (rPspA) antigen specified by pYA3494 induced protective anti-rPspA-specific immune responses (Kang et al. (2002) Infect. Immun. 70, 1739-1749). A recombinant plasmid pYA3496 specifying a His(6)-tagged rPspA (His(6)-rPspA) protein (no apparent signal sequence) caused the rPspA antigen to localize to the cytoplasm of Salmonella. Salmonella vaccines carrying pYA3494 or pYA3496 expressed similar amounts of rPspA. After a single oral immunization in BALB/c mice with 10(9) colony-forming units (CFU) of the recombinant Salmonella vaccines carrying pYA3494 or pYA3496, IgG antibody responses were stimulated to both rPspA and Salmonella lipopolysaccharide (LPS) antigens. The anti-rPspA IgG titer induced by Salmonella carrying pYA3494 (1.9 X 10(7)) was 10(4) times higher than induced by Salmonella carrying pYA3496 (< 2.4 X 10(3)). (C) 2003 Federation of European Microbiological Societies. Published by Elsevier Science B.V. All rights reserved.