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载体预激发对表达幽门螺杆菌脲酶A和B的减毒活重组伤寒沙门氏菌Ty21a疫苗在人类志愿者中免疫原性的影响。

Impact of vector-priming on the immunogenicity of a live recombinant Salmonella enterica serovar typhi Ty21a vaccine expressing urease A and B from Helicobacter pylori in human volunteers.

作者信息

Metzger W G, Mansouri E, Kronawitter M, Diescher S, Soerensen M, Hurwitz R, Bumann D, Aebischer T, Von Specht B-U, Meyer T F

机构信息

Max-Planck-Institut für Infektionsbiologie, Abteilung Molekulare Biologie, Schumannstrasse 21/22, D-10117 Berlin, Germany.

出版信息

Vaccine. 2004 Jun 2;22(17-18):2273-7. doi: 10.1016/j.vaccine.2003.11.020.

Abstract

Orally administered recombinant Salmonella vaccines represent an attractive option for mass vaccination programmes against various infectious diseases. Therefore, it is crucial to gather knowledge about the possible impact of preexisiting immunity to carrier antigens on the immunogenicity of recombinant vaccines. Thirteen volunteers were preimmunized with Salmonella typhi Ty21a in order to evaluate the effects of prior immunization with the carrier strain. Then, they received three doses of 1-2 x 10(10) viable organisms of either the vaccine strain S. typhi Ty21a (pDB1) expressing subunits A and B of recombinant Helicobacter pylori urease (n = 9), or placebo strain S. typhi Ty21a (n = 4). Four volunteers were preimmunized and boosted with the vaccine strain S. typhi Ty21a (pDB1). No serious adverse effects were observed in any of the volunteers. Whereas none of the volunteers primed and boosted with the vaccine strain responded to the recombinant antigen, five of the nine volunteers preimmunized with the carrier strain showed cellular immune responses to H. pylori urease (56%). This supports the results of a previous study in non-preimmunized volunteers where 56% (five of nine) of the volunteers showed a cellular immune response to urease after immunisation with S. typhi Ty21a (pDB1).

摘要

口服重组沙门氏菌疫苗是大规模疫苗接种计划对抗各种传染病的一个有吸引力的选择。因此,了解对载体抗原的预先存在的免疫力对重组疫苗免疫原性的可能影响至关重要。13名志愿者用伤寒沙门氏菌Ty21a进行了预先免疫,以评估用载体菌株预先免疫的效果。然后,他们接受了三剂1-2×10(10)个活生物体的疫苗菌株伤寒沙门氏菌Ty21a(pDB1),该菌株表达重组幽门螺杆菌脲酶的亚基A和B(n = 9),或安慰剂菌株伤寒沙门氏菌Ty21a(n = 4)。4名志愿者用疫苗菌株伤寒沙门氏菌Ty21a(pDB1)进行了预先免疫和加强免疫。在任何志愿者中均未观察到严重不良反应。在用疫苗菌株进行初次免疫和加强免疫的志愿者中,没有人对重组抗原有反应,而在用载体菌株进行预先免疫的9名志愿者中,有5名对幽门螺杆菌脲酶表现出细胞免疫反应(56%)。这支持了先前在未预先免疫的志愿者中进行的一项研究结果,其中56%(9名中的5名)的志愿者在用伤寒沙门氏菌Ty21a(pDB1)免疫后对脲酶表现出细胞免疫反应。

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