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用重组痘苗病毒免疫的小鼠对麻疹病毒血凝素的黏膜和全身免疫反应

Mucosal and systemic immune responses to measles virus haemagglutinin in mice immunized with a recombinant vaccinia virus.

作者信息

Etchart N, Wild F, Kaiserlian D

机构信息

INSERM U 404 Immunity and Vaccination, Institut Pasteur de Lyon, France.

出版信息

J Gen Virol. 1996 Oct;77 ( Pt 10):2471-8. doi: 10.1099/0022-1317-77-10-2471.

Abstract

The immune response to a vaccinia virus recombinant expressing the measles virus haemagglutinin (VV-HA) was compared after parenteral or mucosal immunizations in mice. Parenteral immunizations with 10(6) p.f.u. VV-HA induced HA-specific antibody-producing cells (IgG>IgA) and HA-specific class I-restricted cytotoxic T lymphocytes (CTL) in the spleen. In contrast, intranasal administrations of 10(6) p.f.u. of VV-HA induced HA-specific spot-forming cells in the spleen (IgG>IgA) and the lungs (IgA>IgG), and HA-specific CTL in the spleen. Co-immunization by the nasal route with VV-HA and cholera toxin enhanced HA-specific immune responses. Oral immunizations with 10(8) p.f.u. of VV-HA generated low numbers of HA-specific IgA-producing cells in the lamina propria of the gut, and a weak HA-specific CTL activity in the spleen and mesenteric lymph nodes. Oral co-immunization with VV-HA and cholera toxin greatly enhanced the level of HA-specific spot-forming cells in the lamina propria (IgA>IgG). Interestingly, intrajejunal immunizations with 10(8) p.f.u. VV-HA alone induced high levels of anti-HA IgG-producing cells in the spleen and anti-HA IgA-secreting cells in the lamina propria of the gut. These data show that (i) VV-HA by the nasal route is immunogenic and generates a measles-specific mucosal immune response in the lung, which represents the primary site of replication of measles virus and that (ii) VV-HA can also induce measles-specific immunity in the intestine provided that it is protected from degradation in the gastrointestinal tract, or that cholera toxin is used as an adjuvant.

摘要

在小鼠中,比较了经肠胃外或粘膜免疫后对表达麻疹病毒血凝素的痘苗病毒重组体(VV-HA)的免疫反应。用10⁶ 蚀斑形成单位(p.f.u.)的VV-HA进行肠胃外免疫可诱导脾脏中产生HA特异性抗体的细胞(IgG>IgA)和HA特异性I类限制性细胞毒性T淋巴细胞(CTL)。相比之下,经鼻给予10⁶ p.f.u.的VV-HA可诱导脾脏(IgG>IgA)和肺脏(IgA>IgG)中产生HA特异性斑点形成细胞,以及脾脏中的HA特异性CTL。经鼻途径将VV-HA与霍乱毒素共同免疫可增强HA特异性免疫反应。用10⁸ p.f.u.的VV-HA进行口服免疫可在肠道固有层中产生少量HA特异性IgA产生细胞,并在脾脏和肠系膜淋巴结中产生较弱的HA特异性CTL活性。将VV-HA与霍乱毒素进行口服共同免疫可大大提高固有层中HA特异性斑点形成细胞的水平(IgA>IgG)。有趣的是,单独用10⁸ p.f.u.的VV-HA进行空肠内免疫可在脾脏中诱导高水平的抗HA IgG产生细胞,并在肠道固有层中诱导抗HA IgA分泌细胞。这些数据表明:(i)经鼻途径给予的VV-HA具有免疫原性,并在肺中产生麻疹特异性粘膜免疫反应,而肺是麻疹病毒的主要复制部位;(ii)只要VV-HA在胃肠道中不被降解,或者使用霍乱毒素作为佐剂,它也可以在肠道中诱导麻疹特异性免疫。

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