Immunization of pigs with a particle-mediated DNA vaccine to influenza A virus protects against challenge with homologous virus
Immunization of pigs with a particle-mediated DNA vaccine to influenza A virus protects against challenge with homologous virus
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DOI：
10.1128/jvi.72.2.1491-1496.1998
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发表时间：
1998-02-01
影响因子：
5.4
通讯作者：
Swain, WF
中科院分区：
文献类型：
--
作者：
Macklin, MD;McCabe, D;Swain, WF
将编码甲型H1N1流感病毒血凝素(HA)的DNA表达载体(A/Swin/Indiana/1726/88)通过颗粒介导的方式传递到猪的表皮，可在同型攻击后引起体液免疫反应并加速病毒的清除。在抑制初始病毒感染方面，粘膜注射HA表达载体引起的免疫反应与表皮接种引起的免疫反应有本质上的不同。相比之下，将编码A/PR/8/34(H1N1)流感病毒核蛋白的质粒输送到表皮可引起强烈的体液反应，但在鼻腔病毒脱落方面没有可检测到的保护作用。将HA DNA疫苗的效力与商业上可获得的灭活全病毒疫苗的效力以及先前感染所提供的免疫水平进行了比较。HA DNA疫苗和灭活病毒疫苗产生了类似的保护作用，因为最初的感染没有得到预防，但随后感染的扩大是有限的，从而使病毒早日清除。从强毒猪流感病毒中恢复过来的恢复期动物在受到攻击时完全抵抗感染。甲型H1N1流感病毒系统是一种与人类相关的临床前模型，无论是疾病还是基因转移到表皮，都为推进DNA疫苗的开发提供了基础。
Particle-mediated delivery of a DNA expression vector encoding the hemagglutinin (HA) of an H1N1 influenza virus (A/Swine/Indiana/l726/88) to porcine epidermis elicits a humoral immune response and accelerates the clearance of virus in pigs following a homotypic challenge. Mucosal administration of the HA expression plasmid elicits an immune response that is qualitatively different than that elicited by the epidermal vaccination in terms of inhibition of the initial virus infection. In contrast, delivery of a plasmid encoding an influenza virus nucleoprotein from A/PR/8/34 (H1N1) to the epidermis elicits a strong humoral response but no detectable protection in terms of nasal virus shed. The efficacy of the HA DNA vaccine was compared with that of a commercially available inactivated whole-virus vaccine as well as with the level of immunity afforded by previous infection. The HA DNA and inactivated viral vaccines elicited similar protection in that initial infection was not prevented, but subsequent amplification of the infection is limited, resulting in early clearance of the virus. Convalescent animals which recovered from exposure to virulent swine influenza virus were completely resistant to infection when challenged. The porcine influenza A virus system is a relevant preclinical model for humans in terms of both disease and gene transfer to the epidermis and thus provides a basis for advancing the development of DNA-based vaccines.