Recombinant nipah virus vaccines protect pigs against challenge

Recombinant nipah virus vaccines protect pigs against challenge
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DOI:
10.1128/jvi.00263-06
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发表时间:
2006-08-01
影响因子:
5.4
通讯作者:
Czub, Markus
Czub, Markus
中科院分区:
医学2区
文献类型:
--
作者:
Weingartl, Hana M.;Berhane, Yohannes;Czub, Markus

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尼帕病毒(Nipah virus,NiV)属于副粘病毒科,于1999年在马来西亚从一次严重的人类脑炎爆发中的死亡病例中分离出来,当时人类感染与猪传播病毒有关。因此,能够消除病毒散毒的猪疫苗具有兽医和人类健康利益。使用携带NiV糖蛋白(ALVAC-G)或融合蛋白(ALVAC-F)基因的基于金丝雀痘病毒的疫苗载体,以每组10(8)PFU或组合方式肌内免疫每组4头猪。猪在接种后14天加强免疫,两周后用2.5 × 10(5)PFU NiV攻毒。ALVAC-F/G联合疫苗诱导了最高水平的中和抗体(2,560);尽管F疫苗接种者的中和抗体水平较低(160),但所有接种动物似乎都能抵抗攻毒。攻毒后未从任何接种疫苗猪的组织中分离出病毒,实时逆转录(RT)-PCR检测仅在几个样品中检测到少量病毒RNA。在攻毒对照猪中,从许多组织中分离病毒(10(4.4)PFU/g)或通过实时RT-PCR检测病毒。ALVAC-F/G疫苗接种者的疫苗接种似乎刺激1型和2型细胞因子应答。组织学检查结果表明,接种疫苗者的病变没有增强。与攻毒对照猪相反,在接种动物中未检测到病毒散毒,攻毒对照猪从咽喉和鼻中分离出病毒(10(2.9)PFU/ml)。根据所提供的数据,ALVAC-F/G联合疫苗似乎是一种非常有前途的猪用候选疫苗。
Nipah virus (NiV), of the family Paramyxoviridae, was isolated in 1999 in Malaysia from a human fatality in an outbreak of severe human encephalitis, when human infections were linked to transmission of the virus from pigs. Consequently, a swine vaccine able to abolish virus shedding is of veterinary and human health interest. Canarypox virus-based vaccine vectors carrying the gene for NiV glycoprotein (ALVAC-G) or the fusion protein (ALVAC-F) were used to intramuscularly immunize four pigs per group, either with 10(8) PFU each or in combination. Pigs were boosted 14 days postvaccination and challenged with 2.5 x 10(5) PFU of NiV two weeks later. The combined ALVAC-F/G vaccine induced the highest levels of neutralization antibodies (2,560); despite the low neutralizing antibody levels in the F vaccinees (160), all vaccinated animals appeared to be protected against challenge. Virus was not isolated from the tissues of any of the vaccinated pigs postchallenge, and a real-time reverse transcription (RT)-PCR assay detected only small amounts of viral RNA in several samples. In challenge control pigs, virus was isolated from a number of tissues (10(4.4) PFU/g) or detected by real-time RT-PCR. Vaccination of the ALVAC-F/G vaccinees appeared to stimulate both type 1 and type 2 cytokine responses. Histopathological findings indicated that there was no enhancement of lesions in the vaccinees. No virus shedding was detected in vaccinated animals, in contrast to challenge control pigs, from which virus was isolated from the throat and nose (10(2.9) PFU/ml). Based on the data presented, the combined ALVAC-F/G vaccine appears to be a very promising vaccine candidate for swine.