Garg Rajni, Kaur Manpreet, Saxena Ankur, Prasad Rajendra, Bhatnagar Rakesh
Laboratory of Molecular Biology and Genetic Engineering, School of Biotechnology, Jawaharlal Nehru University, New Delhi, 110067 Delhi, India; Amity Institute of Biotechnology, Amity University, Gurgaon (Manesar), 122413 Haryana, India.
Laboratory of Molecular Biology and Genetic Engineering, School of Biotechnology, Jawaharlal Nehru University, New Delhi, 110067 Delhi, India; Vaccine and Infectious Disease Research Center, Translational Health Science and Technology Institute, NCR Biotech Science Cluster, 3(rd) Milestone, Faridabad-Gurgaon Expressway, Faridabad, 121001 Haryana, India.
Mol Immunol. 2017 May;85:166-173. doi: 10.1016/j.molimm.2017.02.011. Epub 2017 Mar 6.
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 LD 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 2IU/ml and total RVNA titer was observed to be 4IU/ml which is eight times higher than the minimum protective titer recommended by WHO. Furthermore, it conferred 80% protection against challenge with 50 LD 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.
狂犬病是一个全球范围内备受关注的问题。尽管狂犬病疫苗早已问世，但它们的效力、安全性、可及性和成本效益一直是重大问题。这就需要改进狂犬病疫苗接种策略。在这方面，DNA疫苗具有巨大潜力。DNA疫苗pgp.LAMP - 1能使BALB/c小鼠在受到20倍半数致死量的狂犬病攻击病毒标准（CVS）毒株攻击时获得60%的保护。添加Emulsigen - D后，该疫苗制剂能提供完全的致死攻击保护。为评估这种疫苗制剂用于人类的可行性，它与其他美国食品药品监督管理局（FDA）批准的佐剂，即明矾、免疫疫苗、Montanide ISA720 VG一起进行了测试。在狂犬病DNA疫苗中添加明矾后，观察到增强的免疫反应与高IgG抗体滴度、偏向Th2的反应以及高水平的狂犬病病毒中和抗体（RVNAs）和IgG1/IgG2a比值>1相关。总IgG抗体滴度为2IU/ml，总RVNA滴度为4IU/ml，这比世界卫生组织推荐的最低保护滴度高八倍。此外，按照美国国立卫生研究院（NIH）推荐的狂犬病效力测试标准，该疫苗制剂在受到50倍半数致死量的狂犬病CVS毒株攻击时能提供80%的保护。此前，我们已根据FDA的Y表指南以及欧洲药品评估局的指南确定了该疫苗的临床前安全性。当以10倍推荐剂量给Wistar大鼠注射时，该疫苗在注射部位以及全身水平均未显示出明显毒性。因此，用明矾补充狂犬病DNA疫苗pgp.LAMP - 1将有助于开发一种无毒、有效、稳定且价格合理的疫苗，可用于对抗困扰发展中国家的大量致命狂犬病感染。
