title: Alum adjuvanted rabies DNA vaccine confers 80% protection against lethal 50 LD50rabies challenge virus standard strain.
abstract: 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 LD50rabies 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 LD50of 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.
authors.affiliation: 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.
authors.forename: Rajni
authors.initials: R
authors.lastname: Garg
authors.affiliation: 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.
authors.forename: Manpreet
authors.initials: M
authors.lastname: Kaur
authors.affiliation: Laboratory of Molecular Biology and Genetic Engineering, School of Biotechnology, Jawaharlal Nehru University, New Delhi, 110067 Delhi, India; Fish Health Division, Diagnostic Virology Laboratory, ICAR-Directorate of Coldwater Fisheries Research, Anusandhan Bhawan, Industrial Area, Bhimtal 263136, District Nainital, Uttarakhand, India.
authors.forename: Ankur
authors.initials: A
authors.lastname: Saxena
authors.affiliation: Amity Institute of Biotechnology, Amity University, Gurgaon (Manesar), 122413 Haryana, India.
authors.forename: Rajendra
authors.initials: R
authors.lastname: Prasad
authors.affiliation: Laboratory of Molecular Biology and Genetic Engineering, School of Biotechnology, Jawaharlal Nehru University, New Delhi, 110067 Delhi, India. Electronic address: rakeshbhatnagar@jnu.ac.in.
authors.forename: Rakesh
authors.initials: R
authors.lastname: Bhatnagar
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000534:Alum Compounds / Q000494:pharmacology*; D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D007928:Lethal Dose 50; D051379:Mice; D008807:Mice, Inbred BALB C; D011819:Rabies Vaccines / Q000276:immunology*; D019444:Vaccines, DNA / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D011819:Rabies Vaccines; D019444:Vaccines, DNA; C041524:aluminum sulfate
keywords: Adjuvants; Challenge; DNA vaccine; Encephalitis; Protective efficacy