1. Nonclinical safety evaluation of oral recombinant anti-human papilloma virus vaccine (RHPV 1618): Regulatory toxicology studies in mice, rats and rabbits - An innovative approach
- Author
-
P. Uday Kumar, Rajkumar Hemalatha, K. Narendra Babu, B. Dinesh Kumar, M.V. Surekha, S.S.Y.H. Qadri, Nemani Harishankar, and Y. Srinivasa Reddy
- Subjects
Dose ,Adolescent ,Ty21a ,030231 tropical medicine ,Human Papilloma Virus Vaccine ,Physiology ,Immunotoxicology ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Oral administration ,Animals ,Humans ,030212 general & internal medicine ,Papillomavirus Vaccines ,Human papillomavirus 16 ,General Veterinary ,General Immunology and Microbiology ,Papillomavirus Infections ,Public Health, Environmental and Occupational Health ,Salmonella typhi ,Acute toxicity ,Rats ,Infectious Diseases ,Toxicity ,Molecular Medicine ,Nasal administration ,Capsid Proteins ,Female ,Rabbits - Abstract
AIM The human papilloma virus (HPV) type 16 and 18 causes nearly 70% of uterine cervical cancers. Oral administration of live Salmonella typhi Ty21a, expressing major capsid proteins (L1) of HPV 16 and 18 is a potential choice for immunization in adolescent girls under low resource settings. Present study aimed to assess the nonclinical safety of recombinant S. typhi expressing HPV 16 and 18 (rStHPV) proteins. METHODOLOGY The acute toxicity of rStHPV was tested by intranasal single dose administration, of 10 and 50 folds higher than clinical prophylactic dose, in mice and rat followed by monitoring their survival for 14 days. Sub-chronic toxicity was evaluated in rats and rabbits with prophylactic and 5 times (average) to clinical prophylactic dosages on scheduled days (1st, 3rd & 5th day) through oral and intranasal routes. The immune/allergic response of rStHPV was assessed in mice through intranasal and intra-peritoneal routes. Experimental animals were daily monitored for live phase, and clinical chemistry, haematology, immunotoxicology, immunogenic response and histopathological examination of vital organs on 15th, 29th and 93rd days. RESULTS No abnormal changes were noticed in live phase activity, clinical chemistry and haematology profile. The gross necropsy, organ weights and histopathology were found to be normal. No immunotoxicity was recorded as evaluated by tier I tests. Allergic immune response, as evaluated with IgE levels was also negative irrespective of test routes. On the other hand, a significant (P
- Published
- 2020