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首页> 外文期刊>Infection and immunity >Immune Responses to Recombinant Pneumococcal PspA Antigen Delivered by Live Attenuated Salmonella enterica Serovar Typhimurium Vaccine
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Immune Responses to Recombinant Pneumococcal PspA Antigen Delivered by Live Attenuated Salmonella enterica Serovar Typhimurium Vaccine

机译：减毒活沙门氏菌血清型鼠伤寒疫苗对重组肺炎球菌PspA抗原的免疫应答。

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Attenuated Salmonella enterica serovar Typhimurium expressing recombinant antigens from other pathogens elicits primarily a Th1-type dominant immune response to both recombinant and Salmonella antigens. The immunogenicity and appropriate subcellular location of the recombinant antigen in the Salmonella vaccine strain may contribute to augmenting immune responses by facilitating adequate exposure of recombinant antigen to antigen-presenting cells for processing. To allow for secretion from gram-negative bacteria and overexpression of antigen, a DNA fragment encoding a highly antigenic α-helical region of PspA (pneumococcal surface protein A) was subcloned downstream from the β-lactamase signal sequence in the multicopy Asd+ pYA3493 vector to create pYA3494. pYA3493 was derived from a class of Asd+ vectors with reduced expression of Asd to minimize selective disadvantage and enhance immunization of expressed recombinant antigens. The S. enterica serovar Typhimurium vaccine strain was constructed by the introduction of deletion mutations Δcrp-28 and ΔasdA16. Approximately 50% of the recombinant PspA (rPspA) expressed in a Salmonella strain harboring pYA3494 was detected in the combined supernatant and periplasmic fractions of broth-grown recombinant Salmonella. After a single oral immunization in BALB/c mice with 109 CFU of the recombinant Salmonella vaccine strain carrying pYA3494, immunoglobulin G (IgG) antibody responses were stimulated to both the heterologous antigen rPspA and Salmonella lipopolysaccharide (LPS) and outer membrane proteins (OMPs). About half, and even more at later times after immunization, of the antibodies induced to rPspA were IgG1 (indicating a Th2-type response), whereas 60 to 70% of the antibodies to LPS and 80 to 90% of those to OMPs were IgG2a (indicating a Th1-type response). A sublethal infection with Streptococcus pneumoniae WU2 boosted PspA antibody levels and maintained IgG2a/IgG1 ratios similar to those seen before the challenge. Oral immunization with Salmonella-PspA vaccine protected 60% of immunized mice from death after intraperitoneal challenge with 50 times the 50% lethal dose of virulent S. pneumoniae WU2.
机译：表达其他病原体重组抗原的减毒 Salmonella 鼠伤寒鼠伤寒沙门氏菌主要引起对重组和 Salmonella 抗原的Th1型显性免疫反应。沙门氏菌疫苗株中重组抗原的免疫原性和适当的亚细胞位置可能通过促进重组抗原充分暴露于抗原呈递细胞进行加工而有助于增强免疫反应。为了允许革兰氏阴性细菌的分泌和抗原的过度表达，在多拷贝Asd 中将编码PspA（肺炎球菌表面蛋白A）的高度抗原性α-螺旋区的DNA片段亚克隆到β-内酰胺酶信号序列的下游。 + pYA3493向量可创建pYA3494。 pYA3493衍生自一类Asd + 载体，其Asd的表达减少，从而最大程度地降低了选择性不利性并增强了表达的重组抗原的免疫性。 S。通过导入缺失突变Δ crp-28 和Δ asdA16 构建了肠炎血清型鼠伤寒疫苗株。在含有pYA3494的 Salmonella 菌株中表达的重组PspA（rPspA）大约有50％在肉汤生长的重组 Salmonella 的上清液和周质部分中检测到。在用10 9 CFU重组pem3494沙门氏菌疫苗株对BALB / c小鼠进行单次口服免疫后，免疫球蛋白G（IgG）抗体对两种异源刺激抗原rPspA和沙门氏菌脂多糖（LPS）和外膜蛋白（OMPs）。免疫后约有一半甚至更多的时间在免疫后诱导的rPspA抗体是IgG1（表明Th2型应答），而LPS抗体的60％至70％和OMPs抗体的80％至90％是IgG2a。 （表示Th1型反应）。肺炎链球菌WU2的亚致死性感染可提高PspA抗体水平，并保持IgG2a / IgG1比值与攻击前相似。用沙门氏菌- PspA疫苗进行的口服免疫可以使腹膜内攻击后60％的免疫小鼠免于死亡，其毒性是50％致死性 S致死剂量的50倍。肺炎 WU2。

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