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首页> 外文期刊>Molecular Immunology >Alum adjuvanted rabies DNA vaccine confers 80% protection against lethal 50 LD50 rabies challenge virus standard strain
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Alum adjuvanted rabies DNA vaccine confers 80% protection against lethal 50 LD50 rabies challenge virus standard strain

机译：Alum Aduvanted狂犬病DNA疫苗赋予80％的免受致死50 LD50狂犬病攻击病毒标准菌株的保护

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摘要

Rabies is a serious concern world-wide. Despite availability of rabies vaccines for long; their efficacy, safety, availability and cost effectiveness has been a tremendous issue. This calls for improvement of rabies vaccination strategies. DNA vaccination has immense potential in this regard. The DNA vaccine pgp.LAMP-1 conferred 60% protection to BALB/c mice against 20 LD50 rabies challenge virus standard (CVS) strain challenge. Upon supplementation with Emulsigen-D, the vaccine formulation conferred complete protection against lethal challenge. To assess the feasibility of this vaccine formulation for human use, it was tested along with other FDA approved adjuvants, namely, Alum, Immuvac, Montanide ISA720 VG. Enhanced immune response correlated with high IgG antibody titer, Th2 biased response with a high level of rabies virus neutralizing antibodies (RVNAs) and IgG1/IgG2a ratio >1, observed upon alum supplementation of the rabies DNA vaccine. The total IgG antibody titer was 2 IU/ml and total RVNA titer was observed to be 4 IU/ml which is eight times higher than the minimum protective titer recommended by WHO. Furthermore, it conferred 80% protection against challenge with 50 LD50 of the rabies CVS strain, conducted in compliance with the potency test for rabies recommended by the National Institutes of Health (NIH), USA. Previously, we have established pre-clinical safety of this vaccine as per the guidelines of Schedule Y, FDA as well as The European Agency for evaluation of Medicinal Products. The vaccine showed no observable toxicity at the site of injection as well as at systemic level in Wistar rats when administered with 10X recommended dose. Therefore, supplementation of rabies DNA vaccine, pgp.LAMP-1 with alum would lead to development of a non-toxic, efficacious, stable and affordable vaccine that can be used to combat high numbers of fatal rabies infections tormenting developing countries. (C) 2017 Elsevier Ltd. All rights reserved.
机译：狂犬病是全世界严重关注的。尽管长期以来，尽管有狂犬病疫苗;他们的功效，安全，可用性和成本效益是一个巨大的问题。这需要改善狂犬病疫苗接种策略。 DNA疫苗接种在这方面具有巨大的潜力。 DNA疫苗PGP.Lamp-1对Balb / C小鼠的60％赋予20 LD50狂犬病攻击病毒标准（CVS）应变挑战。在补充乳果原后，疫苗制剂赋予了完全保护致命挑战。为了评估该疫苗配方的可行性进行人使用，它与其他FDA批准的佐剂进行了测试，即Alum，Immuvac，Montanide ISA720 Vg。增强的免疫应答与高IgG抗体滴度相关，Th2偏置响应具有高水平的狂犬病病毒中和抗体（RVNA）和IgG1 / IgG2a比> 1，在狂犬病DNA疫苗的alum补充时观察到。总IgG抗体滴度为2IU / mL，观察到总rVNA滴度为4IU / mL，比谁推荐的最小保​​护滴度高8倍。此外，它赋予了80％的免受50毫安的狂犬病CVS菌株的攻击保护，该rabies CVS菌株符合美国国家卫生研究院（NIH），美国国家研究院建议的狂犬病的效力试验。此前，我们根据安排y，FDA以及欧洲评估药品评估机构的指导方案建立了该疫苗的前期安全性。当用10x推荐剂量给药时，疫苗在注射部位以及Wistar大鼠的全身水平上显示出可观察到的毒性。因此，补充狂犬病DNA疫苗，PGP.Lamp-1与明矾将导致促进无毒，有效，稳定和实惠的疫苗，可用于打击大量致命狂犬病感染折磨发展中国家。 （c）2017 Elsevier Ltd.保留所有权利。

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