PEDV流行病学、发病机制及免疫预防

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题目：PEDV感染：病原学、流行病学、发病机制及免疫预防

摘要：PEDV是冠状病毒科甲型冠状病毒属的一种，可引起新生仔猪急性腹泻、呕吐、脱水和高死亡率。在过去30年里，PEDV感染对欧洲和亚洲的养猪业造成了重大的经济损失，2013-2014年，美国、加拿大和墨西哥也报告了这种疾病。从2013年4月到现在，PED在美国的流行导致了超过10%的美国猪只的死亡。

PED的重新出现表明，该病毒能够从现有的免疫程序、生物安全和控制系统中逃逸。PED的地方性流行是一个严重的问题，PEDV变异株的出现加剧了这一问题。PEDV传播迅速，可以造成猪只大量死亡。这些毒株具有高度的肠致病性，可急性感染小肠和大肠的绒毛上皮细胞，空肠和回肠是原发部位。PEDV感染可引起仔猪急性萎缩性肠炎，并伴有病毒血症，导致呕吐和严重腹泻，接着大面积脱水，这也是哺乳仔猪死亡的主要原因。我们需要全面了解流行性或地方性PEDV毒株的致病特征，以便在受影响地区预防和控制该疾病，并开发有效的疫苗。

Immunoprophylaxis as a preventive strategy

Epidemic PED

When PED occurs in a seronegative breeding farm, immunization or vaccination of pregnant sows is important in the control of epidemic PED and to reduce the number of deaths of suckling piglets. If the sows are due to farrow within 2 weeks or more, immunization can be undertaken by exposure to virulent autogenous virus, such as fecal slurry or minced intestines from infected neonatal piglets. However, there is a potential risk of incidental widespread infection of other pathogenic viruses, such as PCV2, contained in the PEDV-infected piglets’ feces or intestines among sows or their suckling piglets via vertical transmission routes (Jung et al., 2006c;Park et al., 2009; Ha et al., 2010). The importance and mechanisms of passive lactogenic immunity to provide newborn piglets with immediate protection against TGEV infection have been reviewed by Saif et al. (2012).

All strains of epidemic PEDV in Europe, Asia and the US are highly enteropathogenic, as evidenced by the high mortality of infected nursing piglets. However, attenuation of the virulence of Korean (KPEDV-9 and DR13) or Japanese (83P-5) PEDV strains could be induced through high cell-culture passages (93rd–100th) (Kweon et al., 1999; Song et al., 2007; Sato et al., 2011). In addition, the attenuated cell-adapted PEDV strains have been used as oral (Korean strain DR13 only) or intramuscular (IM) live virus vaccines. The IM administration of live attenuated KPEDV-9 PEDV vaccine (1 mL of 107 TCID50/mL; twice at 2 or 4 weeks before farrowing) reduced the 40% mortality rate of piglets challenged with five 50% lethal dose (LD50) of the parent wild-type strain and the 100% mortality rate of piglets challenged with 10 LD50 to 0% and 80%, respectively (Kweon et al., 1999).

The efficacy might be associated with high PEDV specific IgG levels in the serum and colostrum of vaccinated sows (Song et al.,2007). A study using IM live attenuated DR13 PEDV vaccine (1 mL of 107 TCID50/mL; twice at 2 or 4 weeks before farrowing) reduced the 100% mortality of piglets challenged with a high-dose of the parent DR13 to 60% (Song et al., 2007). Based on these observations, pregnant sows can be vaccinated using live attenuated PEDV strains via an IM route, but induction of complete protection was not observed in the nursing piglets.

免疫预防作为一种PED预防策略

在血清学阴性种猪场妊娠母猪分娩前进行免疫接种，对控制PED的流行和减少哺乳仔猪的死亡具有重要意义。对2周后即将分娩的妊娠母猪，既可免疫接种也可进行返饲（使用新生仔猪粪便或肠道匀浆进行）。当然返饲可能存在着垂直传播其他致病性病毒的潜在风险。Saif等综述了被动乳源性免疫的重要性和机制。

在欧洲、亚洲和美国流行的PEDV毒株具有高度的肠道致病性，从感染的哺乳仔猪高死亡率就可以看出这一点。然而，韩国(KPEDV-9和DR13)、日本(83P-5) PEDV毒株的毒力致弱可以通过细胞培养高传代诱导。此外，细胞适应的PEDV毒株已被用作口服(仅韩国株DR13)或肌注(IM)弱毒疫苗。KPEDV-9 PEDV弱毒疫苗(1mL 107TCID50/mL；在分娩前2周、4周免疫)能降低40%的仔猪死亡率。

这种效果可能与接种母猪血清和初乳中PEDV特异性IgG水平高有关。使用DR13 PEDV弱毒疫苗(1mL 107TCID50/mL；在分娩前2周、4周免疫)将高剂量DR13攻毒的仔猪死亡率从100%降低到60%。根据这些观察，PEDV弱毒株可通过IM途径接种妊娠母猪，但在哺乳仔猪中未观察到诱导完全保护作用。

Endemic PED

Active immunization of nursing or feeder pigs is important for the control of endemic PEDV infections (Saif et al., 2012). A field study (Song et al., 2007) showed that compared to vaccination via IM route, oral administration with live attenuated PEDV (DR13 strain) vaccine twice 2 or 4 weeks before farrowing was more effective in boosting or initiating immunity in pregnant sows and their suckling piglets (3-day-old). The vaccinated sows and their piglets exhibited higher IgA (mucosal immunity) and virus neutralization antibody (humoral immunity) levels in the colostrum or sera compared to those of the counterparts administered the IM vaccine with the same dose. However, the presence of maternal antibodies in vaccinated pigs can interfere with active antibody production after PEDV infection, as observed in TGEV infection (Sestak et al., 1996; Saif et al., 2012). Whether the oral live vaccine strain is genetically stable and remains non-infectious in the fields needs to be further studied.

PED的地方流行

猪只的主动免疫对于控制流行性PEDV感染非常重要。研究表明，与传统意义上通过肌注接种相比，在分娩前2、4周口服PEDV弱毒疫苗(韩国DR13株)对妊娠母猪提高或启动免疫力更有效。接种的母猪在初乳或血清中表现出较高的IgA(粘膜免疫)和病毒中和抗体(体液免疫)水平。然而，正如在TGEV感染中观察到的那样，接种疫苗的猪体内母源抗体存在会干扰PEDV感染后主动免疫抗体的产生。口服弱毒疫苗病毒株在遗传上是否稳定，在田间是否仍具有非传染性，还需要进一步研究。

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