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绵羊、山羊和小牛用减毒活 Rift Valley 热重组 arMP-12ΔNSm21/384 疫苗候选物的安全性和免疫原性。

Safety and immunogenicity of a live attenuated Rift Valley Fever recombinant arMP-12ΔNSm21/384 vaccine candidate for sheep, goats and calves.

机构信息

Research and Development Dept., Multi-Chemical Industry, Lot. 157, Z I, Sud-Ouest (ERAC) B.P.: 278, Mohammedia 28810, Morocco.

Department of Biological Sciences, University of Texas at El Paso, El Paso, TX 79968, USA.

出版信息

Vaccine. 2019 Mar 14;37(12):1642-1650. doi: 10.1016/j.vaccine.2019.01.067. Epub 2019 Feb 14.

DOI:10.1016/j.vaccine.2019.01.067
PMID:30773401
Abstract

Rift Valley fever (RVF) causes serious health and economic losses to the livestock industry as well as a significant cause of human disease. The prevention of RVF in Africa is a global priority, however, available vaccines have only been partially effective. Therefore, the objective of this study was to evaluate the safety and immunogenicity of a live, attenuated recombinant RVFV arMP-12ΔNSm21/384 nucleotide deletion vaccine candidate in domestic ruminants. Evaluation involved testing to determine the infectivity titer of the vaccine virus in Vero cells for industrial scale up vaccine production. Safety experiments were conducted to determine the potential of the vaccine virus to revert to virulence by serial passages in sheep, the possibility of virus spread from vaccinated sheep and calves to unvaccinated animals, and the potential health effects of administering overdoses of the vaccine to sheep, goats and calves. The immunogenicity of 3 doses of 10, 10 and 10 Tissue Culture Infectious Doses (TCID) of the vaccine was assessed in 3 groups of 10 sheep and 3 groups of 10 goats, and doses of 10, 10 and 10 TCID was evaluated in 3 groups of 10 calves subcutaenous vaccintation. The results showed that the infectivity titer of the vaccine virus was 10 TCID/ml, that the vaccine did not spread from vaccinated to un-vaccinated animals, there was no evidence of reversion to virulence in sheep and the vaccine overdoses did not cause any adverse effects. The immunogenicity among sheep, goats and calves indicated that doses of 10-10 TCID elicited detectable antibody by day 7 post-vaccination (PV) with antibody titers ranging from 0.6 log to 2.1 log on day 14 PV with sustained titers through day 28 PV. Overall, these findings indicated that the RVFV arMP-12ΔNSm21/384 vaccine is a promising candidate for the prevention of RVF among domestic ruminants.

摘要

裂谷热(RVF)对畜牧业造成严重的健康和经济损失,也是人类疾病的重要病因。非洲裂谷热的预防是全球的重点,然而,现有的疫苗仅部分有效。因此,本研究的目的是评估活减毒重组 RVFV arMP-12ΔNSm21/384 核苷酸缺失疫苗候选物在国内反刍动物中的安全性和免疫原性。评估包括测试以确定疫苗病毒在 Vero 细胞中的感染滴度,以进行工业规模的疫苗生产。安全性实验旨在确定疫苗病毒在绵羊中连续传代后回复毒力的潜力、从接种疫苗的绵羊和小牛传播病毒的可能性以及向未接种疫苗的动物传播的可能性,以及向绵羊、山羊和小牛过量接种疫苗对健康的潜在影响。将 3 个剂量(10、10 和 10 组织培养感染剂量(TCID))的疫苗接种到 3 组 10 只绵羊和 3 组 10 只山羊中,并评估 3 组 10 只小牛皮下接种 10、10 和 10 TCID 的剂量。结果表明,疫苗病毒的感染滴度为 10 TCID/ml,疫苗不会从接种动物传播到未接种动物,在绵羊中没有证据表明毒力回复,疫苗过量接种不会引起任何不良反应。绵羊、山羊和小牛的免疫原性表明,10-10 TCID 剂量在接种后第 7 天(PV)可检测到抗体,第 14 天 PV 的抗体滴度为 0.6 至 2.1 对数,PV 第 28 天仍保持持续滴度。总的来说,这些发现表明 RVFV arMP-12ΔNSm21/384 疫苗是预防国内反刍动物裂谷热的一种有前途的候选疫苗。

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