Research Groups
Mammalian Biology: Recombinant Gene Products
Research Interests and Description
Group Leader: Navin Khanna, MSc, PhDGroup Members
Research Interests
Dengue vaccine, Diagnostics, Antivirals.Description of Research
Current research focuses on genetically engineered bio-molecules of medical use. The primary contribution is in the development of novel recombinant designer proteins as inexpensive, highly sensitive and specific diagnostic intermediates for viral infections, like HCV and Dengue virus. Diagnostic kits based on these proteins have been commercialized. These designer proteins are also being used for developing novel reporter assays using Terbium-labeled nanoparticles. In addition, laboratory-scale “know-how” has been developed for the production of recombinant HBsAg, anti-HBsAg antibody and IFN-g. Other research interests include pathogenesis of Dengue virus and development of experimental Dengue tetravalent subunit vaccine in yeast.Recombinant dengue vaccine development
Dengue vaccine development efforts in the lab continue to be directed towards the major envelope (E) protein of the dengue viruses, which contains the host receptor-recognition motif as well as numerous neutralizing epitopes. However, as it is becoming increasingly apparent that the key attributes of the E protein, as a vaccine candidate, map to a discrete region called domain III (EDIII), the lab has developed experimental dengue vaccine candidates based on the EDIIIs of all four prevalent dengue virus serotypes using eukaryotic expression systems. The Groups’ data show that a recombinant EDIII-based tetravalent protein produced in the yeast Pichia pastoris can elicit a neutralizing immune response, specific to each one of the four dengue virus serotypes, in mice. The lab has filed a patent on this and has just initiated collaboration with an industry partner to accelerate the development of this vaccine candidate.
Recombinant multiepitope proteins for dengue diagnosis
The lab has developed a novel, cost-effective strategy to create recombinant proteins of diagnostic utility. This entails the splicing together of key epitopes into a single chimeric protein that can be over-expressed in E. coli. This approach eliminates the need for multiple peptide synthesis and time consuming virus culture for antigen production. The Group has created two multiepitope proteins based on dengue virus epitopes, one specific for IgG antibodies and the other, for IgM antibodies. An evaluation of these proteins using a large panel of ~170 sera demonstrated the utility of these proteins in identifying dengue infections with a high degree of sensitivity and specificity. The lab has developed a second generation molecule, based on EDIII, which is capable of picking up both IgG and IgM type anti-dengue virus antibodies. The Group has demonstrated the diagnostic utility of this protein using a panel of 289 human sera. This has been patented.
Dengue virus inhibitors
A new programme has recently been initiated aimed at identifying agents with anti-dengue activity from herbal sources. This programme will also seek to develop a library of dengue NS3 protease inhibitors to identify potential small molecular weight dengue virus inhibitors. This work has been undertaken in collaboration with a pharmaceutical company.
Recent Publications
Etemad, B., Batra, G., Raut, R., Dahiya, S., Khanam, S., Swaminathan, S., Khanna, N. 2008. An envelope domain III-based chimeric antigen produced in Pichia pastoris elicits neutralizing antibodies against all four dengue virus serotypes. Am J Trop Med Hyg. 79, 353-63
Hapugoda, M.D., Batra, G, Abeyewickreme, W., Swaminathan, S., Khanna, N. 2007. Single antigen detects both immunoglobulin M (IgM) and IgG antibodies elicited by all four dengue virus serotypes. Clinical Vaccine Immunol 14, 1505-1514
Khanam, S., Rajendra, P., Khanna, N., Swaminathan, S. 2007. An adenovirus prime/plasmid boost strategy for induction of equipotent immune responses to two dengue virus serotypes. BMC Biotechnol. 7, 10
AnandaRao, R., Swaminathan, S., Fernando, S., Jana, A.M., Khanna, N. 2006. Recombinant multiepitope protein for the early detection of dengue infections. Clin. Vaccine Immunol. 13, 59-67
Bose, B., Khanna, N., Acharya, S.K., Sinha, S. 2006. Generation and characterization of a single- gene mouse-human chimeric antibody against Hepatitis B surface antigen. J Gastroenterol Hepatol. 21, 1439-1447
Bose, B., Khanna, N., Acharya, S.K., Sinha, S. 2006. Generation and characterization of a high affinity chimaeric antibody against Hepatitis B surface antigen. Biotechnol Appl Biochem. 43, 93-101
Patents
Batra, G., Hapugoda, M., Chaudhry, S., Swaminathan, S., Khanna, N. Tetravalent dengue specific domain III based chimeric recombinant protein. PCT/IN06/00316Khanna, N. and Swaminathan, S. A novel dengue envelope domain III-based tetravalent protein vaccine. 1259/DEL/2007
