title: Nonclinical toxicology study of recombinant-plasmid DNA anti-rabies vaccines.
abstract: The absence of standard guidelines from National and International regulatory agencies for the safety evaluation of biotechnology products challenges the ingenuity of toxicologists. At present, the development of standard pre-clinical toxicology protocols for such products is on an individual case basis. The present investigation is an attempt to evaluate the safety profile of the first indigenously developed DNA based anti-rabies vaccine in India. The test compounds were DNA rabies vaccine [DRV (100 microg)] and combination rabies vaccine (CRV (100 microg DRV and 1/50 dose of cell culture vaccine)), intended for clinical use by intramuscular route on 1, 7, 14 and 28 day. As per the regular mandatory requirements, the study has been designed to undertake acute (single dose--10 days), sub-chronic (repeat dose--28 days) and chronic (intended clinical dose--120 days) toxicity tests using three dose levels viz. therapeutic, average (2 x therapeutic dose) and highest dose (10 x therapeutic dose) exposure in Swiss Albino mice. The selection of the rodent model viz. Swiss Albino mice is based on affinity and rapid higher antibody response during the efficacy studies. Apart from physical, physiological, clinical, hematological and histopathology profiles of all target organs, the tier-I immunotoxicity parameters have also been monitored. There were no observational adverse effects even at levels of 10x therapeutic dose administration of DRV and CRV. The procedure also emphasizes on the designing of protocols for the products developed by recombinant technique.
authors.affiliation: National Institute of Nutrition, (Indian Council of Medical Research), Hyderabad, Andhra Pradesh 500007, India.
authors.forename: P Uday
authors.initials: PU
authors.lastname: Kumar
authors.forename: B Dinesh
authors.initials: BD
authors.lastname: Kumar
authors.forename: V V
authors.initials: VV
authors.lastname: Annapurna
authors.forename: T Prasanna
authors.initials: TP
authors.lastname: Krishna
authors.forename: S
authors.initials: S
authors.lastname: Kalyanasundaram
authors.forename: P
authors.initials: P
authors.lastname: Suresh
authors.forename: N
authors.initials: N
authors.lastname: Harishankar
authors.forename: V
authors.initials: V
authors.lastname: Jagadeesan
authors.forename: S
authors.initials: S
authors.lastname: Hariharan
authors.forename: A Nadamuni
authors.initials: AN
authors.lastname: Naidu
authors.forename: Kamala
authors.initials: K
authors.lastname: Krishnaswamy
authors.forename: P N
authors.initials: PN
authors.lastname: Rangarajan
authors.forename: V A
authors.initials: VA
authors.lastname: Srinivasan
authors.forename: G S
authors.initials: GS
authors.lastname: Reddy
authors.forename: B
authors.initials: B
authors.lastname: Sesikeran
mesh_terms: D000818:Animals; D005260:Female; D008297:Male; D051379:Mice; D011819:Rabies Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000633:toxicity*; D023382:Toxicity Tests, Acute; D036401:Toxicity Tests, Chronic; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000633:toxicity*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000633:toxicity
chemical_list: D011819:Rabies Vaccines; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic