Vaccination of pigs with a DNA construct expressing an influenza virus M2-nucleoprotein fusion protein exacerbates disease after challenge with influenza A virus
Vaccination of pigs with a DNA construct expressing an influenza virus M2-nucleoprotein fusion protein exacerbates disease after challenge with influenza A virus
复制标题
DOI：
10.1099/0022-1317-83-8-1851
复制
发表时间：
2002-08-01
影响因子：
3.8
通讯作者：
Bianchi, ATJ
中科院分区：
文献类型：
--
作者：
Heinen, PP;Rijsewijk, FA;Bianchi, ATJ
在小鼠中，诱导针对M2蛋白的胞外结构域（M2e）的抗体的疫苗可赋予对甲型流感病毒感染的保护。与表面糖蛋白、血凝素和神经氨酸酶不同，M2的该结构域高度保守，因此是潜在的广谱免疫原。在本研究中，在猪的猪流感攻击模型中评价了诱导抗I抗体的疫苗所赋予的保护。评价由We和B型肝炎病毒核心蛋白（M2eHBc）之间的融合产生的蛋白质，有或没有佐剂。此外，评估表达We与流感病毒核蛋白（M2eNP）之间的融合蛋白的DNA构建体，以观察由抗体赋予的广谱保护是否可以通过T辅助细胞和细胞毒性T细胞进一步增强。所有疫苗均诱导针对M2e的抗体应答，并且M2eNP DNA疫苗还诱导流感病毒特异性淋巴细胞增殖应答。然而，在用猪流感病毒（HIN 1）攻击后，与未接种对照组相比，在接种组中未观察到保护作用。相反，免疫猪比对照猪表现出更严重的临床体征。接种M2eNP DNA的猪表现出最严重的临床体征，6头猪中有3头在攻毒后第1天和第2天死亡。这些结果表明，抗We的抗体，特别是与细胞介导的免疫应答结合，会加重疾病。因此，在使用We作为免疫原的进一步研究中应密切观察感染后的临床体征，并且在人体中使用We时应谨慎。
In mice, vaccines inducing antibodies to the extracellular domain of the M2 protein (M2e) can confer protection to influenza A virus infection. Unlike the surface glycoproteins, haemagglutinin and neuraminidase, this domain of M2 is highly conserved and is therefore a potential broad-spectrum immunogen. In this study, the protection conferred by vaccines inducing antibodies to We was evaluated in a challenge model for swine influenza in pigs. A protein resulting from the fusion between We and the hepatitis B virus core protein (M2eHBc), with or without adjuvant, was evaluated. In addition, a DNA construct expressing a fusion protein between We and influenza virus nucleoprotein (M2eNP) was evaluated to see if the broad-spectrum protection conferred by antibodies could be further enhanced by T helper cells and cytotoxic T cells. All vaccines induced an antibody response against M2e, and the M2eNP DNA vaccine additionally induced an influenza virus-specific lymphoproliferation response. However, after challenge with a swine influenza virus (H IN 1), no protection was observed in the vaccinated groups compared with the non-vaccinated control group. On the contrary, vaccinated pigs showed more severe clinical signs than the control pigs. The M2eNP DNA-vaccinated pigs showed the most severe clinical signs and three out of six pigs died on days 1 and 2 post-challenge. These results indicate that antibodies to We, especially in combination with cell-mediated immune responses, exacerbate disease. Thus, clinical signs after infection should be observed closely in further studies using We as an immunogen and caution should be exercised in using We in humans.