中文摘要：本研究应用γ-射线和合成Mn-十肽-磷酸盐复合物（MnDpPi）构建了一种新型的抗委内瑞拉马脑炎病毒（VEEV）和基孔贡亚病毒（CHIKV）疫苗；Mn-十肽-磷酸盐复合物是通过锰-肽正磷酸盐抗氧化剂在极端耐射线辐射球菌中累积形成的。本研究结果表明，通过该方法构建的疫苗能够为小鼠提供有效的抗病毒保护作用。将MnDpPi与VEEV、CHIKV相结合能够产生持续的抗原表位的保护作用，即使是在超致死剂量的γ-射线辐照情况下也能维持抗原表位的保护作用。体外试验检测到辐射病毒完全失活。将VEEV灭活后与MnDpPi联合免疫能够显著提高疫苗的保护效率。因此，基于MnDpPi的γ-射线灭活手段可以用于任何目标抗原疫苗的制备，且该技术具有速度快、费用低的优点。
外文摘要：Over the last ten years, Chikungunya virus (CHIKV), an Old World alphavirus has caused numerous outbreaks in Asian and European countries and the Americas, making it an emerging pathogen of great global health importance. Venezuelan equine encephalitis virus (VEEV), a New World alphavirus, on the other hand, has been developed as a bioweapon in the past due to its ease of preparation, aerosol dispersion and high lethality in aerosolized form. Currently, there are no FDA approved vaccines against these viruses. In this study, we used a novel approach to develop inactivated vaccines for VEEV and CHIKV by applying gamma-radiation together with a synthetic Mn-decapeptide-phosphate complex (MnDpPi), based on manganous-peptide-orthophosphate antioxidants accumulated in the extremely radiation-resistant bacterium Deinococcus radiodurans. Classical gamma-irradiated vaccine development approaches are limited by immunogenicity-loss due to oxidative damage to the surface proteins at the high doses of radiation required for complete virus-inactivation. However, addition of MnDpPi during irradiation process selectively protects proteins, but not the nucleic acids, from the radiation-induced oxidative damage, as required for safe and efficacious vaccine development. Previously, this approach was used to develop a bacterial vaccine. In the present study, we show that this approach can successfully be applied to protecting mice against viral infections. Irradiation of VEEV and CHIKV in the presence of MnDpPi resulted in substantial epitope preservation even at supra-lethal doses of gamma-rays (50,000 Gy). Irradiated viruses were found to be completely inactivated and safe in vivo (neonatal mice). Upon immunization, VEEV inactivated in the presence of MnDpPi resulted in drastically improved protective efficacy. Thus, the MnDpPi-based gamma inactivation approach described here can readily be applied to developing vaccines against any pathogen of interest in a fast and cost-effective manner.
外文关键词：Venezuelan equine encephalitis virus； Chikungunya virus； Deinococcus radiodurans； Inactivated vaccine； MnDpPi； Aerosol challenge
作者：Gayen, M; Gupta, P; Morazzani, EM; Gaidamakova, EK; Knollmann-Ritschel, B; Daly, MJ; Glass, PJ; Maheshwari, RK
作者单位：美国卫生科学军队服务大学
期刊名称：VACCINE
期刊影响因子：3.33
出版年份：2017
出版刊次：6
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