Alum adjuvanted rabies DNA vaccine confers 80% protection against lethal 50 LD50 rabies challenge virus standard strain
Alum adjuvanted rabies DNA vaccine confers 80% protection against lethal 50 LD50 rabies challenge virus standard strain
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DOI：
10.1016/j.molimm.2017.02.011
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发表时间：
2017-05-01
影响因子：
3.6
通讯作者：
Bhatnagar, Rakesh
中科院分区：
文献类型：
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作者：
Garg, Rajni;Kaur, Manpreet;Bhatnagar, Rakesh
狂犬病是世界范围内的一个严重问题。尽管狂犬病疫苗的可用性很长时间，但其有效性，安全性，可用性和成本效益一直是一个巨大的问题。这就要求改进狂犬病疫苗接种策略。DNA疫苗在这方面具有巨大的潜力。LAMP-1 DNA疫苗对BALB/c小鼠抗20 LD_（50）狂犬病攻毒标准株（CVS）攻击的保护率为60%。在补充Emulsigen-D后，疫苗制剂赋予针对致死性攻击的完全保护。为了评估该疫苗制剂用于人类使用的可行性，将其与其他FDA批准的佐剂（即明矾、Immuvac、Montanide ISA 720 VG）一起进行沿着测试。在狂犬病DNA疫苗的明矾补充后观察到，增强的免疫应答与高IgG抗体滴度、Th 2偏向应答与高水平的狂犬病病毒中和抗体（RVNA）和IgG 1/IgG 2a比率>1相关。总IgG抗体滴度为2 IU/ml，观察到总RVNA滴度为4 IU/ml，比WHO推荐的最低保护滴度高8倍。此外，它对50 LD 50狂犬病CVS菌株的攻击具有80%的保护作用，该攻击是按照美国国立卫生研究院（NIH）推荐的狂犬病效价试验进行的。之前，我们已经根据FDA和欧洲药品评价机构的附表Y指南确定了该疫苗的临床前安全性。当以10倍推荐剂量给药时，疫苗在注射部位以及Wistar大鼠全身水平均未显示出可观察到的毒性。因此，用明矾补充狂犬病DNA疫苗pgp.LAMP-1将导致开发无毒、有效、稳定和负担得起的疫苗，其可用于对抗折磨发展中国家的大量致命狂犬病感染。(C)2017爱思唯尔有限公司版权所有
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.