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一种重组鼠伤寒沙门氏菌疫苗通过四种不同的免疫途径诱导局部免疫。

A recombinant Salmonella typhimurium vaccine induces local immunity by four different routes of immunization.

作者信息

Hopkins S, Kraehenbuhl J P, Schödel F, Potts A, Peterson D, de Grandi P, Nardelli-Haefliger D

机构信息

Institute of Biochemistry, University of Lausanne, Switzerland.

出版信息

Infect Immun. 1995 Sep;63(9):3279-86. doi: 10.1128/iai.63.9.3279-3286.1995.

Abstract

Immunization of mice with an attenuated Salmonella typhimurium strain (Phopc) carrying a plasmid encoding a hybrid form of the hepatitis B virus core antigen (HBc) induced specific antibody responses against the bacterial lipopolysaccharide (LPS) and HBc. Different mucosal routes of immunization, i.e., oral, nasal, rectal, and vaginal, were compared for their ability to induce a systemic as well as a mucosal response at sites proximal or distant to the site of immunization. Anti-LPS and anti-HBc immunoglobulin A (IgA) antibodies were measured in saliva, in feces, and in genital, bronchial, and intestinal secretions. Specific antibodies in serum and secretions were observed after immunization via all routes; however, the response to LPS was independent of that against HBc. In serum, saliva, and genital and bronchial secretions, high amounts of anti-HBc IgA were obtained by the nasal route of immunization. Vaginal immunization resulted in two different responses in mice: high and low. We observed a correlation between the level of specific immune response and the estrous status of these mice at the time of immunization. Rectal immunization induced high amounts of IgA against HBc and LPS in colonorectal secretions and feces but not at distant sites. These data suggest that S. typhimurium is able to invade different mucosal tissues and induce long-lasting local IgA responses against itself and a carried antigen after a single immunization.

摘要

用携带编码乙型肝炎病毒核心抗原(HBc)杂交形式质粒的减毒鼠伤寒沙门氏菌菌株(Phopc)免疫小鼠,可诱导针对细菌脂多糖(LPS)和HBc的特异性抗体反应。比较了不同的黏膜免疫途径,即口服、鼻腔、直肠和阴道途径,以评估它们在免疫部位近端或远端诱导全身及黏膜反应的能力。检测了唾液、粪便以及生殖、支气管和肠道分泌物中的抗LPS和抗HBc免疫球蛋白A(IgA)抗体。通过所有途径免疫后,在血清和分泌物中均观察到特异性抗体;然而,对LPS的反应与对HBc的反应无关。在血清、唾液以及生殖和支气管分泌物中,鼻腔免疫途径可产生大量抗HBc IgA。阴道免疫在小鼠中产生了两种不同的反应:高反应和低反应。我们观察到这些小鼠在免疫时特异性免疫反应水平与发情状态之间存在相关性。直肠免疫在结直肠分泌物和粪便中诱导产生大量针对HBc和LPS的IgA,但在远处部位则不然。这些数据表明,鼠伤寒沙门氏菌能够侵入不同的黏膜组织,并在单次免疫后诱导针对自身和携带抗原的持久局部IgA反应。

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