裂谷热MP-12诱变和重组裂谷热arMP12ΔNsm21/384候选疫苗在坦桑尼亚本土牛、绵羊和山羊种群中的免疫原性评价

L. Salekwa, Nyundo Sb, Adamson Ek, M. Matiko, Bettinger Ge, Rowl, Jm, Pedro Palermo, P. Wambura, J. Morrill, D. Watts
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Methods: Six to nine months old goats (Capra aegagrus hircus), calves (Bos taurus indicus) and sheep (Ovis aries) were vaccinated subcutaneously with one ml each of 1 × 105 plaque forming units (PFU)/ml of the RVF MP-12 and/or the arMP-12ΔNSm21/384 candidate vaccines. The controls included six animals, two of each species which received 1 ml of Eagle's Minimum Essential Medium as a placebo. Blood samples were collected on day 2 before vaccination, and on the day (0) immediately before vaccination were tested for RVFV antibody to insure that only antibody negative animals were used in the vaccine trials. Samples collected on days, 3, 4, 5, 7 post-vaccination (PV) to determine the possibility of a vaccine induced viremia, and on days 4, 5, 7, 14, 21, 28, 35, 42 and 67 to determine the immune response of the vaccinated animals. Sera samples were tested for RVFV RNA by RT-PCR and for infectious virus in Vero E6 cells. The immune response was determined by testing sera samples for antibody using a commercial IDVERT ELISA kit (Montpellier-France) as well as a plaque reduction neutralization test (PRNT). Animals were observed daily for adverse effects and rectal temperature was recorded at the time of blood collection. Results: All vaccinated animals developed RVFV neutralizing antibodies with titers ranging from 1:10 in some animals as early as day 4 and 5 PV to as high as 1:160-1:2560 over the 67 day study period with no adverse effect observed in any of the animals. The antibody titers of goats to both MP-12 and arMP-12ΔNSm21/384 vaccines was significantly higher than the response observed for sheep and cattle. A viremia was not detected in any of the vaccinated and control animals. 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引用次数: 1

摘要

目的:裂谷热病毒(RVFV)是在大多数非洲国家和阿拉伯半岛的家畜反刍动物和人类中造成毁灭性暴发的原因。目前正在开发和评估一种改进的兽医疫苗,以预防家畜反刍动物中的裂谷热疾病,其中包括一种减毒裂谷热MP-12候选活疫苗和一种重组疫苗,即arMP12ΔNsm21/384,该疫苗是从裂谷热MP-12候选疫苗衍生出来的。本研究的目的是在坦桑尼亚国内反刍动物中评估这些裂谷热病毒候选疫苗。方法:6 ~ 9月龄山羊(Capra aegagrus hircus)、犊牛(Bos taurus indicus)和绵羊(Ovis aries)皮下接种裂谷热MP-12和/或arMP-12ΔNSm21/384候选疫苗(1 × 105斑块形成单位/ml)各1 ml。对照组包括6只动物,每种2只,接受1毫升Eagle’s Minimum Essential Medium作为安慰剂。在疫苗接种前第2天采集血样,并在疫苗接种前第0天检测裂谷热病毒抗体,以确保只有抗体阴性的动物用于疫苗试验。在接种后第3、4、5、7天采集样本,以确定疫苗诱导病毒血症的可能性,并在第4、5、7、14、21、28、35、42和67天采集样本,以确定接种动物的免疫反应。采用RT-PCR检测血清样本中的RVFV RNA和Vero E6细胞中的感染性病毒。免疫反应是通过使用商用IDVERT ELISA试剂盒(法国蒙彼利埃)和斑块减少中和试验(PRNT)检测血清样本的抗体来确定的。每天观察动物的不良反应,并在采血时记录直肠温度。结果:在67天的研究期间,所有接种疫苗的动物都产生了RVFV中和抗体,滴度从一些动物在第4天和第5天的1:10到高达1:160-1:2560,没有观察到任何动物的不良反应。山羊对MP-12和arMP-12ΔNSm21/384疫苗的抗体滴度明显高于绵羊和牛。未在任何接种疫苗的动物和对照动物中发现病毒血症。结论:本研究结果表明,通过SC途径接种的RVFV MP-12和arMP12ΔNsm21/384候选疫苗在坦桑尼亚的牛、绵羊和山羊的本地物种中引发了RVFV中和抗体,因此值得进一步研究以评估这些候选疫苗在家养反刍动物中的安全性和保护功效。
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Evaluation of the Immunogenicity of a Mutagenized Rift Valley Fever MP-12 and a Recombinant Rift Valley Fever arMP12ΔNsm21/384 Vaccine Candidates in Indigenous Species of Cattle, Sheep, and Goats in Tanzania
Objective: Rift valley fever virus (RVFV) is the cause of devastating outbreaks among domestic ruminants and humans in most African countries and in the Arabian Peninsula. Current efforts to develop and evaluate an improved veterinary vaccine to prevent RVF disease among domestic ruminants includes a live attenuated RVFV MP-12 candidate and a recombinant vaccine referred to as arMP12ΔNsm21/384 that was derived from the RVF MP-12 vaccine candidate. The aim of this study was to evaluate these RVFV vaccine candidates in domestic ruminants in Tanzania. Methods: Six to nine months old goats (Capra aegagrus hircus), calves (Bos taurus indicus) and sheep (Ovis aries) were vaccinated subcutaneously with one ml each of 1 × 105 plaque forming units (PFU)/ml of the RVF MP-12 and/or the arMP-12ΔNSm21/384 candidate vaccines. The controls included six animals, two of each species which received 1 ml of Eagle's Minimum Essential Medium as a placebo. Blood samples were collected on day 2 before vaccination, and on the day (0) immediately before vaccination were tested for RVFV antibody to insure that only antibody negative animals were used in the vaccine trials. Samples collected on days, 3, 4, 5, 7 post-vaccination (PV) to determine the possibility of a vaccine induced viremia, and on days 4, 5, 7, 14, 21, 28, 35, 42 and 67 to determine the immune response of the vaccinated animals. Sera samples were tested for RVFV RNA by RT-PCR and for infectious virus in Vero E6 cells. The immune response was determined by testing sera samples for antibody using a commercial IDVERT ELISA kit (Montpellier-France) as well as a plaque reduction neutralization test (PRNT). Animals were observed daily for adverse effects and rectal temperature was recorded at the time of blood collection. Results: All vaccinated animals developed RVFV neutralizing antibodies with titers ranging from 1:10 in some animals as early as day 4 and 5 PV to as high as 1:160-1:2560 over the 67 day study period with no adverse effect observed in any of the animals. The antibody titers of goats to both MP-12 and arMP-12ΔNSm21/384 vaccines was significantly higher than the response observed for sheep and cattle. A viremia was not detected in any of the vaccinated and control animals. Conclusions: The findings of this study demonstrated that the RVFV MP-12 and arMP12ΔNsm21/384 vaccine candidates administered by the SC route elicited RVFV neutralizing antibodies in indigenous species of cattle, sheep, and goats in Tanzania, and therefore warrants further studies to assess the safety and protective efficacy of these vaccine candidates in domestic ruminants.
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