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蘇少儀

Vaccinology of classical swine fever: from lab to field
J.T van Oirschot
Virus Discovery Unit, ID-Lelystad, PO Box 65, 8200 AB Lelystad, The Netherlands
Abstract
There are two types of classical swine fever vaccines  available: the classical live and the recently developed E2  subunit  vaccines . The live Chinese strain  vaccine  is the most widely used. After a single vaccination, it confers solid immunity within a few days that appears to persist lifelong. The E2  subunit  vaccine  induces immunity from approximately 10–14 days after a single vaccination. The immunity may persist for more than a year, but is then not complete. The Chinese strain  vaccine  may establish a strong herd immunity 1–2 weeks earlier than the E2  vaccine . The ability of the Chinese  vaccine  strain to prevent congenital infection has not been reported, but the E2  subunit  vaccine  does not induce complete protection against congenital infection. Immunological mechanisms that underlie the protective immunity are still to be elucidated. Both types of  vaccine  are considered to be safe. A great advantage of the E2  subunit  vaccine  is that it allows differentiation of infected pigs from vaccinated pigs and is referred to as a DIVA  vaccine . However, the companion diagnostic Erns ELISA to actually make that differentiation should be improved. Many approaches to develop novel  vaccines  have been described, but none of these is likely to result in a new DIVA  vaccine  reaching the market in the next 5–10 years.
Countries where classical swine fever is endemic can best control the infection by systematic vaccination campaigns, accompanied by the normal diagnostic procedures and control measures. Oral vaccination of wild boar may contribute to lowering the incidence of classical swine fever, and consequently diminishing the threat of virus introduction into domestic pigs. Free countries should not vaccinate and should be highly alert to rapidly diagnose any new outbreak. Once a new introduction of classical swine fever virus in dense pig areas has been confirmed, an emergency vaccination programme should be immediately instituted, for maximum benefit. The question is whether the time is ripe to seriously consider global eradication of classical swine fever virus.

蘇少儀

Vaccinology of classical swine fever: from lab to field
J.T van Oirschot
Virus Discovery Unit, ID-Lelystad, PO Box 65, 8200 AB Lelystad, The Netherlands
4. Efficacy
4.1. Vaccination—challenge experiments in pigs免疫攻毒試驗
4.1.1. C-strain豬瘟活毒疫苗的效力
Although not many standard vaccination-challenge experiments have been published the efficacy of the C-strain  vaccine  in preventing clinical CSF seems to approach 100%. Most data from laboratory studies indicate a very high level of protection against the development of clinical signs after challenge, irrespective of the challenge strains used (Aynaud, 1988 and [Vandeputte et al., 2001] ). Piglets can be successfully vaccinated from 1 day of age (Szent-Ivanyi, 1977 and [Vandeputte et al., 2001] ).Already 2–4 days after vaccination, some protection against challenge with a virulent field virus has been reported ( [Kaden and Glaner, 1982] and Lai et al., 1982), and 7 days after a single vaccination it appeared to be complete (Lai et al., 1982, [Biront et al., 1987] , [Terpstra et al., 1990] , [Dahle and Liess, 1995] and [De Smit et al., 2001b] ). Pigs challenged intranasally between 1 and 4 weeks after vaccination did not even appear to have a secondary type antibody response after challenge, which may underpin the presence of a ‘sterile’ immunity (Dahle and Liess, 1995). On the other hand, vaccinated pigs that were intranasally challenged after 26 weeks did show a significant rise in neutralising antibody titre after challenge (Terpstra et al., 1990). The vaccinal protection lasted at least 6–18 months (Szent-Ivanyi, 1977, Aynaud, 1988, [Terpstra et al., 1990] , [Ferrari, 1992] and [Kaden and Lange, 2001] ), but it may even be lifelong: Terpstra (unpublished results) observed that sows vaccinated during a field campaign and challenged in the laboratory 6–7 years later, still remained healthy, whereas two unvaccinated control sows died from the  CSFV  challenge.
Vaccination with the C-strain not only induced virtually complete protection against disease, but also complete ‘virological’ protection or ‘sterile immunity’, in the sense that challenged pigs did not show viraemia nor excreted the challenge virus, even when the challenge was only 1 week after vaccination ( [Ferrari, 1992] , [Dahle and Liess, 1995] , [De Smit et al., 2001b] and Dewulf et al., 2002a). In pigs given a sub-optimal dose of live  vaccine ,  CSFV  antigen of the challenge virus could be demonstrated in tonsils for weeks after challenge (Leunen and Strobbe, 1977). Whether these pigs could actually transmit the challenge virus was not shown. When the virus titre in the  vaccine  was enhanced to normal levels, this ‘carrier’ phenomenon no longer occurred (Biront et al., 1987), suggesting that the creation of carriers by infection of vaccinated pigs should not be regarded as a disadvantage if vaccination is carried out correctly.
Maternal antibodies ingested through colostrum protect young piglets against mortality due to CSF; this protection declines as piglets grow older and maternal antibody titres decrease ( [Terpstra, 1977] and [Launais et al., 1978] ). However, challenge of maternally immune pigs does lead to CSF viral replication (Biront et al., 1987). In addition, it is well known that maternally derived antibodies can markedly suppress the protective immune responses induced by vaccination (Szent-Ivanyi, 1977). The higher the maternal antibody titres at vaccination, the stronger the inhibition of the development of vaccinal immunity ( [Lai et al., 1980] , Aynaud, 1988 and [Vandeputte et al., 2001] ). In the latter study, it was found that pigs with maternal antibodies that were born from vaccinated sows and were vaccinated shortly after the ingestion of colostrums succumbed from challenge 10 weeks later, whereas pigs with maternal antibodies that were vaccinated at 7 weeks of age all survived a challenge 3 weeks later; the unvaccinated control pigs all died. When piglets were vaccinated before ingestion of colostrum they were protected against challenge (Lee et al., 1982 and [Vandeputte et al., 2001] ).
With regard to emergency vaccination, it is of utmost importance whether it can rapidly stop the spread of field virus. Although  vaccines  are primarily developed to confer immunity against disease, another benefit is that the infectious agent will replicate less efficiently in a vaccinated animal and will be transmitted less well to other pigs. In addition, vaccination may render the pig less susceptible to infection, in other words: more virus may be needed to initiate an infection. These processes reduce the spread of a virus in a herd, i.e. generate herd immunity. The ratio of virus transmission in epidemiological terms is expressed as R (reproduction ratio) (De Jong and Kimman, 1994 M.C.M. De Jong and T.G. Kimman, Experimental quantification of  vaccine -induced reduction in virus transmission.  Vaccine ,  12  (1994), pp. 761–766. Article |  PDF (610 K) | | View Record in Scopus | | Cited By in Scopus (122)De Jong and Kimman, 1994). When transmission occurs, R is often greater than 1. When transmission does not take place or only at a very low level, at a rate of R lower than 1, then an outbreak will stop. Against this background, various transmission experiments have been performed with E2  subunit  vaccines , but hardly any with the C-strain  vaccine . Some recent studies indicate that pigs given the C-strain  vaccine  7 days before challenge did not transmit challenge virus to vaccinated, in-contact pigs ( [De Smit et al., 2001b] and Dewulf et al., 2002a). Hence, pigs vaccinated with the C-strain appear to be completely protected after 1 week, maybe even earlier (Dewulf, 2002). When pigs were given a C-strain  vaccine  1, 2 or 4 days after having been inoculated with a virulent  CSFV  strain, they died from CSF, indicating that vaccination after infection seems to have no or little influence on the outcome of the infection (Urbaneck et al., 1973).

蘇少儀

Vaccinology of classical swine fever: from lab to field
J.T van Oirschot
Virus Discovery Unit, ID-Lelystad, PO Box 65, 8200 AB Lelystad, The Netherlands
4. Efficacy
4.1. Vaccination—challenge experiments in pigs免疫攻毒試驗
4.1.2. E2  subunit  vaccine 次單位疫苗的效力
The efficacy of the two commercially available E2  subunit  vaccines  has been extensively assessed in vaccination-challenge experiments in pigs. The amount of E2 protein is, as expected, a decisive factor for the efficacy of the  vaccine  (Bouma et al., 1999). After a single vaccination, the E2  subunit  vaccines  induced hardly any clinical protection in 7 days and moderate protection in 10 days ( [Bouma et al., 2000] and [Uttenthal et al., 2001] ). A single vaccination usually conferred full clinical protection after 14 days against oral or intranasal challenge ( [Bouma et al., 2000] and [Uttenthal et al., 2001] ). However, in another experiment where pigs were challenged intramuscularly, no protection was measured 14 days after vaccination: four out of four pigs died or were killed in a moribund state (Ziegler and Kaden, 2002). Protection has been measured for 13 months after a single vaccination, although two out of eight vaccinated pigs died after challenge (De Smit et al., 2001a).
A second vaccination with E2  subunit  vaccines  markedly improved the clinical protection. When pigs were vaccinated twice at an interval of 4 weeks and challenged 2 weeks after the second vaccination they appeared to be virtually completely protected ( [Dewulf et al., 2001] and [Ziegler and Kaden, 2002] ).
Virological protection, often measured as (absence of) viraemia or virus titres in oral or nasal swabs, does not necessarily coincide with clinical protection after challenge. In two studies ( [Bouma et al., 2000] and [Uttenthal et al., 2001] ), the E2  subunit  vaccines  induced a marked virological protection, i.e. a reduction in the number of pigs developing viraemia or shedding virus from 10 or 14 days after a single vaccination, but not in a third study (Ziegler and Kaden, 2002). At 21 days after vaccination, viraemia was still detected after challenge in some pigs (Uttenthal et al., 2001). A double vaccination with an interval of 28 days protected half or all of the pigs against developing viraemia ( [Dewulf et al., 2001] and [Ziegler and Kaden, 2002] ). Viraemia was not prevented in gilts that were vaccinated twice and infected by contact (Dewulf et al., 2002b).
As expected, the immunity induced by an E2  subunit  vaccine  is also inhibited by maternal antibodies (Klinkenberg et al., 2002).
With regard to prevention or reduction of transmission of challenge virus, it has been reported that when pigs were challenged 7 days after vaccination, all vaccinated in-contact pigs became infected. Ten days after vaccination none (Bouma et al., 2000) or most of the contact pigs became infected (Uttenthal et al., 2001). After vaccination-challenge intervals of 14 and 21 days, the results of different studies on transmission of challenge virus did not agree. In one study (Bouma et al., 2000) no transmission was demonstrated, in an other one (Uttenthal et al., 2001) there was considerable transmission. This discrepancy may have been due to methodological differences, to the different  vaccines  used or to the use of specified-pathogen-free pigs versus conventionally raised pigs. An Aujeszky’s disease virus  vaccine  had been shown to be more efficacious with respect to prevention of transmission of field virus in specified-pathogen-free than in conventional pigs (Van Nes et al., 2001). A third explanation may be that in the experiments of Bouma et al. (2000), the homologous virus was used for challenge: the E2 was derived from the Brescia strain and the challenge virus was also the Brescia strain. In the study of Uttenthal et al. (2001), a challenge virus of a subtype other than that of the strains that delivered the E2 in the  vaccines  was used.  CSFV  is antigenically more homogenous than BVDV, but antigenic variation does exist (Wensvoort, 1989 and [Edwards and Sands, 1990] ). When pigs were challenged 3–6 months after a single vaccination, virus transmission to unvaccinated, in-contact pigs did not occur in two out of the three experiments (De Smit et al., 2001a). A double vaccination did not prevent infection of gilts and pigs that were exposed to  CSFV  by indirect contact with infected pigs ( [Dewulf et al., 2001] , [Dewulf et al., 2002b] and | Cited By in Scopus (3)[Ziegler and Kaden, 2002] ). However, in the study of Ziegler and Kaden (2002), there were also groups of twice-vaccinated pigs that did not transmit  CSFV  to one unvaccinated in-contact pig.
Based on the above it can be concluded that the results of vaccination-challenge and transmission studies on E2  subunit  vaccines  were rather variable.

蘇少儀

Vaccinology of classical swine fever: from lab to field
J.T van Oirschot
Virus Discovery Unit, ID-Lelystad, PO Box 65, 8200 AB Lelystad, The Netherlands
4. Efficacy
4.2. Vaccination-challenge experiments in pregnant sows懷孕母豬的免疫攻毒試驗
When pregnant sows become infected, the virus will be transmitted to the foetuses. This may lead to a variety of consequences of which, from a control point of view, the most undesirable is the birth of persistently infected, immunotolerant, healthy piglets that continuously shed virus (Van Oirschot and Terpstra, 1977). A  vaccine  should be able to prevent these congenital infections. Data on this ability for the C-strain are not available. It may be anticipated that the C-strain prevents congenital infections, because it appears to prevent challenge virus replication virtually completely and has been found to be highly efficacious in the field. However, data on this efficacy criterion should be generated.
The E2  subunit  vaccines  have been demonstrated to be able to reduce, but not to prevent vertical transmission after intranasal or contact challenge. There were great differences between the results of the studies wherein once or twice-vaccinated sows were challenged intranasally and also between the efficacy of the two  vaccines  studied. After one vaccination before or after insemination the challenge virus was detected in foetuses of one out of nine sows (De Smit et al., 2000a) or, depending on the  vaccine  used, in six out of eight or eight out of eight sows (Depner et al., 2001). After a double vaccination, vertical transmission was demonstrated in none of 10 sows (De Smit et al., 2000a), in one of 10 sows (Ahrens et al., 2000), or depending on the  vaccine , in one out of four, or four out of five sows (Depner et al., 2001) and in three out of eight gilts (Dewulf et al., 2002b).
There is no clear explanation for these widely divergent findings: they may be due to, for example, differences in quality of  vaccine  batches, vaccination schedules, challenge virus strains, mode of challenge exposure, and differences in methodology. The interval of 14 days between vaccination and challenge, as was used in the study of Depner et al. (2001), may have been too short to build up an immunity that was sufficient to prevent the challenge virus crossing the placental barrier.

蘇少儀

Vaccinology of classical swine fever: from lab to field
J.T van Oirschot
Virus Discovery Unit, ID-Lelystad, PO Box 65, 8200 AB Lelystad, The Netherlands
7. Immunological mechanisms underlying vaccinal protection
The detailed immunological processes that underlie the protective immunity against CSF are yet to be elucidated.
7.1. Immune responses after C-strain vaccination豬瘟活毒疫苗接種後的各種免疫反應
Vaccination with a C-strain  vaccine  induces neutralising antibodies that usually appear about 2 weeks after vaccination and increase until at least 4–12 weeks ( [Precausta et al., 1983] , [Terpstra et al., 1990] and [Dahle and Liess, 1995] ); they can persist for many years after (a single) vaccination, but also seem to disappear in some pigs (Terpstra and Tielen, 1976). Most of the sows that had been vaccinated once 1–3 years earlier did not respond with an increase in antibody titre upon a second vaccination (Terpstra and Tielen, 1976). When pigs are vaccinated in the presence of maternal antibodies the formation of neutralising antibodies is markedly inhibited. However, when such pigs were vaccinated a second time, many did show a rise in antibody titre after the second vaccination (Terpstra and Wensvoort, 1987).
As early as 6 days after vaccination with a C-strain, interferon-gamma secreting cells specific for  CSFV  were present in the peripheral blood. The presence of these cells can be used as an indicator of cell-mediated immunity (CMI). At that time neutralising antibodies were not detectable, yet the pigs were protected against challenge. This finding and other data on early vaccinal reactions suggest that neutralising antibodies do not play a role in establishing early immunity (Suradhat et al., 2001). It might be that CMI mechanisms are involved in conferring immunity 1 week after challenge. Unpublished data (Terpstra, 1990) show that some sows that had been once vaccinated 6 years earlier had no or very low neutralising antibody titres and yet showed no signs of CSF after challenge. These findings also indicate that the presence of neutralising antibodies at challenge is not a prerequisite for pigs to be protected against CSF. On the other hand, a correlation between the level and presence of neutralising antibodies (at the time of challenge) and protection against challenge has been demonstrated, when challenges were performed not too early after vaccination ( [Terpstra and Wensvoort, 1988] and [Suradhat et al., 2001] ). Terpstra and Wensvoort (1988) found that all pigs that had a neutralising antibody titre of more than 12.5 survived the challenge and all pigs with a titre of more than 32 did not excrete or transmit challenge virus to contact pigs. A secondary type (anamnestic) neutralising antibody response has been described in vaccinated pigs that survived challenge (| Cited By in Scopus (71) [Terpstra and Wensvoort, 1988] , [Suradhat et al., 2001] and [Vandeputte et al., 2001] ). Absence of a clear anamnestic response after challenge has also been observed in pigs surviving challenge (Dahle and Liess, 1995) and in pigs succumbing to challenge (Vandeputte et al., 2001).
Furthermore, pigs with maternally derived neutralising antibodies are passively protected against severe disease and mortality after challenge, indicating a dominant role for antibodies in protective immunity ( [Terpstra, 1977] , Van Bekkum, 1977 and [Biront et al., 1987] ). Van Bekkum (1977) found no correlation between neutralising antibody level and survival after challenge, and Terpstra (1977) did not find a correlation either between fever period and titre of maternally derived neutralising antibodies. However, when distribution of viral antigen in the tonsils was taken as the criterion for protection after challenge, a relation between that criterion and maternal antibody level at challenge was present (Biront et al., 1987).

蘇少儀

Vaccinology of classical swine fever: from lab to field
J.T van Oirschot
Virus Discovery Unit, ID-Lelystad, PO Box 65, 8200 AB Lelystad, The Netherlands
7. Immunological mechanisms underlying vaccinal protection
The detailed immunological processes that underlie the protective immunity against CSF are yet to be elucidated.
7.2. Immune responses after E2  subunit  vaccination次單位疫苗接種後的各種免疫反應
Vaccination with an E2  subunit  vaccine  induced neutralising antibodies and antibodies against E2 within 2–4 weeks after vaccination ( [Bouma et al., 1999] , [Bouma et al., 2000] , [Dewulf et al., 2001] and [Uttenthal et al., 2001] ). The magnitude of the antibody response depended on the amount of E2 in the  vaccine  (Bouma et al., 1999). A second vaccination usually increased the neutralising antibody titres (Hulst et al., 1993), also when E2 mutant proteins were used as immunogens in candidate  vaccines  (Van Rijn et al., 1996). Neutralising antibodies can persist for months; however, 13 months after vaccination, they were no longer detectable in two out of eight pigs ( [De Smit et al., 2001a] and [De Smit et al., 2001b] ). In pregnant sows, neutralising antibodies did not appear until after the second vaccination ( [Ahrens et al., 2000] and [Depner et al., 2001] ). Pigs that had neutralising antibodies at the time of challenge survived, with some exception (| Cited By in Scopus (76)Bouma et al., 1999). Vaccinated pigs that lacked neutralising antibody titres either survived or died after challenge: pigs vaccinated 10–14 days before challenge survived and pigs vaccinated 7 days earlier usually did not survive ( [Bouma et al., 2000] and [Uttenthal et al., 2001] ). In addition, the two pigs that were vaccinated once and had lost all neutralising antibodies at challenge 13 months later died after challenge ( [De Smit et al., 2001a] and [De Smit et al., 2001b] ).

蘇少儀

團長 發表於 2011-12-30 00:03
蘇大覺得OK   兩位就續論吧...

團長你大概沒有看出來
我在回帖的時候考慮到
1.        2007年我用國際畜疫組織（OIE）相關資訊，說次單位疫苗的問題。這次的內容很多就是該相關資訊已修正內容（不過沒有引用相關"公開"的文獻）。
2.        提出的內容不能被對方不勞而穫，集結成冊（教戰守則）。
這些是我難出手的原因
現在我轉貼文獻上有關豬瘟活毒疫苗與次單位疫苗的效力及免疫反應讓他們自己去找答案
他們問的問題上面都有答案，只是要找，要譯…………………..
反正我的結論很簡單，豬瘟活毒疫苗在台灣用了近五十年，上億的豬用過都上市了。全世界用最多的仍是豬瘟活毒疫苗。發生過疫情，在我看過的豬場都是畜主人為管理的問題。不是疫苗的問題。（出了問題，有沒有到現現實地瞭解問題的根源，以尋求解決方案，不能只抱怨豬瘟活毒疫苗這個有缺點，那個有缺點．所以要改用...................產品）。
至於豬瘟活毒疫苗的缺點，用了五十年，都已找出解決方法，有些是他們隨意說，沒有證據。不能解決，那是他們能力的問題，沒有去找問題的根源。

Babyface

郭章燦 發表於 2011-12-30 14:20
大哥我用三台，我家電腦豋入。跑客戶時用iphone豋入，晚上半夜在臥室要回復用ipad，有時睡了沒關機 ...

"'在一个领域里的专家，
在另外一个领域里也许是小学生。'"

現代人
通常都有兩三種資訊上傳方法
沒啥好大驚小怪的

倒是有人用2.3個筆名的
心態才奇怪???

蘇少儀

豬瘟疫情之防治與監控(I)
研究人員  簡茂盛,李維誠,黃千衿,張志成
98 年
LPC疫苗為一活毒減毒疫苗，牧場若不經由豬瘟血清監控，極可能造成母豬移行抗體的干擾，而有無效免疫之情形發生。
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台灣豬場豬瘟疫苗施打前後之抗體表現和病毒RNA 檢出之探討
台彎獸醫誌Taiwan Vet J 36(1)45-54,2010
馬尉真,陳秋麟*,張志成
摘要豬瘟(classical swine fever; CSF) 是台灣豬場重大的病性傳染病，具有高度傳染性和高致死率，對養豬業 者威脅甚鉅。目前台灣在兔化豬瘟疫苗的使用下雖使豬瘟疫情趨緩式微，但仍不斷有零星疫情發生。因此，在田間使
用疫苗後之抗體表現以及是否仍有野外之存在仍有待探討。本研究於台灣地區共20家豬場收集480隻豬隻樣本，每場採24 頭，分別於肉豬第一劑豬瘟疫苗施打前及最後一劑施打後6 週，逢機選取豬隻各12 頭，採取血液及扁桃 腺刮取物。所有血液樣本以商業化豬瘟病抗體檢測套組進行抗體檢測，而扁桃腺刮取物則進行豬瘟病RNA E2及 NS5B基因之反轉錄聚合鏈鎖反應(RT-PCR)和基因定序。ELISA結果顯示，所有20家豬場免疫後良好率約70%， 全部仔豬豬瘟疫苗免疫注射前後之平均blocking 數值分別為62.82% 和73.13%，而E2及NS5B 基因之反轉錄聚合鏈鎖反應(RT-PCR) 檢測結果顯示，有14.2% (34/240) 和17.5% (42/240) 豬隻於免疫前後分別檢出陽性樣本，另外進行E2及NS5B序列比對分析結果顯示，所檢測出的豬瘟病毒皆為疫苗毒，但豬場普遍皆有稍微過早施打第一劑豬瘟疫苗的問題值得注意。

蘇少儀

"過去 18 個月來歐洲有記錄的豬瘟爆發病例數就有數百個之多，今年 ( 1998 ) 7 月初在英國伯明罕舉行的 IPVS ( 國際豬病獸醫學會 ) 大會，豬瘟將是一個熱門話題，會後還有 OIE ( 國際畜疫會 ) 安排以豬瘟為主題的「衛星會議」；相較於近兩年豬瘟的橫行，1996 毛一年內在歐洲共同體只有 55 個豬瘟病例被診斷出來，同年在意大利舉行的 IPVS 大會，豬瘟的口頭報告與海報展示數目合計沒超過 9 個！不過該次大會卻有兩個相當引人注意的特別演講，專門針對豬免疫學的最新發展做討論，比如：已被定義定 E2 抗原的豬瘟病毒非結構蛋白便具有足夠的免疫保護效力，若以 E2 蛋白免疫的豬，除了使此一動物免於受豬瘟野外病毒感染，免疫豬更可以在血清學上被野外豬瘟病毒感染動物清楚區分，所以這種 ( E2 蛋白 ) 次單位疫苗便可以做為「標識免疫」之用；如果此一構想確實可行，歐盟便會開始考慮將目前嚴格執行，不得施打豬瘟疫苗的政策鬆綁"

這是2000年以前的事了
到了2008年輝瑞把銷售許可證繳回，歐盟沒有政策鬆綁