Pigs immunized with a novel E2 subunit vaccine are protected from subgenotype heterologous classical swine fever virus challenge
Pigs immunized with a novel E2 subunit vaccine are protected from subgenotype heterologous classical swine fever virus challenge
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DOI：
10.1186/s12917-016-0823-4
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发表时间：
2016-09-09
影响因子：
2.6
通讯作者：
Shi, Jishu
中科院分区：
文献类型：
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作者：
Madera, Rachel;Gong, Wenjie;Shi, Jishu
背景：猪瘟或猪瘟是一种高度传染性的猪瘟。猪瘟流行国家必须使用改良活病毒(MLV)疫苗的常规疫苗接种，以预防和控制猪瘟。然而，MLV疫苗接种猪和感染CSFV的猪在血清学上是不可能区分的。本研究的目的是开发一种能抵抗CSFV攻击的单剂E2亚单位疫苗。我们推测，由合适的佐剂和天然构象的重组E2组成的疫苗可能会产生与MLV疫苗相似的保护作用。结果：我们的实验疫苗KNB-E2是由昆虫细胞表达的重组E2蛋白(基因1.1)和水包油乳剂佐剂组成的。10头猪(3周龄，每组5头)肌注1剂或2剂(间隔3周)KNB-E2免疫，另10头对照猪只注射生理盐水。第二次免疫后2周，所有接种KNB-E2疫苗的猪和5头对照猪分别接种5×10(5)TCID50 CSFV洪都拉斯/1997疫苗(1.3型，肌肉注射1ml，鼻腔注射1ml)。结果发现，感染CSFV的对照猪在攻击后3-14天停止生长，出现高热(>；40℃)，血液和鼻液中CSFV载量较高，并出现严重的白细胞减少症，而所有接种KNB-E2疫苗的猪与未暴露CSFV的对照猪一样，继续生长，没有任何发热，血液和鼻液中CSFV水平较低或检测不到。在猪瘟病毒攻击时，只有KNB-E2免疫的猪产生了高水平的E2特异性抗体和抗CSFV中和抗体。结论：我们的研究为临床上一剂免疫猪瘟病毒可以保护猪免受CSFV攻击提供了直接证据。这种保护可能是由高水平的E2特异性和抗CSFV中和抗体介导的。
Background: Classical swine fever (CSF) or hog cholera is a highly contagious swine viral disease. CSF endemic countries have to use routine vaccination with modified live virus (MLV) vaccines to prevent and control CSF. However, it is impossible to serologically differentiate MLV vaccinated pigs from those infected with CSF virus (CSFV). The aim of this study is to develop a one-dose E2-subunit vaccine that can provide protection against CSFV challenge. We hypothesize that a vaccine consisting of a suitable adjuvant and recombinant E2 with natural conformation may induce a similar level of protection as the MLV vaccine.Results: Our experimental vaccine KNB-E2 was formulated with the recombinant E2 protein (Genotype 1.1) expressed by insect cells and an oil-in-water emulsion based adjuvant. 10 pigs (3 weeks old, 5 pigs/group) were immunized intramuscularly with one dose or two doses (3 weeks apart) KNB-E2, and 10 more control pigs were administered normal saline solution only. Two weeks after the second vaccination, all KNB-E2 vaccinated pigs and 5 control pigs were challenged with 5 x 10(5) TCID50 CSFV Honduras/1997 (Genotype 1.3, 1 ml intramuscular, 1 ml intranasal). It was found that while control pigs infected with CSFV stopped growing and developed high fever (>40 degrees C), high level CSFV load in blood and nasal fluid, and severe leukopenia 3-14 days post challenge, all KNB-E2 vaccinated pigs continued to grow as control pigs without CSFV exposure, did not show any fever, had low or undetectable level of CSFV in blood and nasal fluid. At the time of CSFV challenge, only pigs immunized with KNB-E2 developed high levels of E2-specific antibodies and anti-CSFV neutralizing antibodies.Conclusions: Our studies provide direct evidence that pigs immunized with one dose KNB-E2 can be protected clinically from CSFV challenge. This protection is likely mediated by high levels of E2-specific and anti-CSFV neutralizing antibodies.