Research Groups

Recombinant Gene Products

Research Interests and Description

Group Leader: Navin Khanna, PhD

Group Members

Research Interests

Recombinant Virus-like-particles as Dengue vaccine candidate, Anti-dengue botanical drug development and Point-of-care multiplexed diagnostics

Description of Research

Recombinant dengue vaccine development
Dengue is a neglected mosquito-borne viral disease that is rapidly spreading globally. Dengue is prevalent in more than 100 countries in the world and is estimated to cause 390 million dengue infections per year with India alone contributing 34% of the infections. Dengue is caused by four serotypes of Dengue viruses (DENV-1, -2, -3 and -4) and all four DENV serotypes are now endemic in India. Dengue infections result in massive economic losses, strained health services, morbidity and mortality, especially among children. The development of vaccine against dengue poses challenge because immune responses to the four DENV serotypes cross react and instead of cross-protection, enhance the disease. Although, a limited use live attenuated virus based dengue vaccine has become available, it has several concerns. The WHO strongly recommends development of next-generation dengue vaccines.
We have developed virus-like-particle (VLP) based Pichia pastoris expressed sub-unit vaccine candidate against dengue. We signed an exclusive agreement with Sun Pharma on October 19, 2016 for the co-development of the dengue vaccine candidate. This vaccine candidate is a tailored recombinant VLP based tetravalent vaccine candidate displaying host cell receptor binding domain, envelope domain III (EDIII), of all four serotypes on the VLP. It has been found to elicit DENV neutralizing antibodies in mice and macaques. The ICGEB- Sun Pharma dengue vaccine candidate is expected to provide a competitive edge over others in all three critical parameters of safety, efficacy & affordability that define an ideal dengue vaccine.
The level of neutralizing and enhancing antibodies generated by a vaccine candidate governs the overall immunity to dengue disease. The VLP based subunit vaccine candidate being developed in our lab has been found to predominantly elicit neutralizing antibodies, without eliciting disease enhancing antibodies, generally associated with whole DENV based vaccine strategies.

Anti-dengue Novel botanical drug development
Currently, there are no available antivirals, which presents a public health challenge in India and other parts of the world, including developed nations. There is no specific treatment other than supportive clinical care, which is extremely difficult in developing countries with poor resources. The dengue menace warrants an urgent need of an affordable and efficacious antiviral. We utilized Ayurveda and bioassay guided approach to screen anti-dengue potential of selected botanical extracts as a solution to this problem. We found Cissampelos pareira (CIPA) to be highly potent against all four DENV serotypes. For its further development as an anti-dengue botanical drug, an exclusive agreement has been signed with Sun Pharma on May 4, 2016. Pre-clinical evaluations are on-going to comply with regulatory standards of India and other regulatory agencies for its registration. This would be followed up with clinical trials. With Dengue being a global public health threat and India being an epicentre, this pan-dengue botanical drug has the potential to provide safe, affordable and effective solution. Moreover, its use is also being explored against Zika virus as Zika and Dengue viruses are phylogenetically similar and co-circulate in many countries. The US FDA has now opened up new avenues for approval of botanical drugs for human use and we plan to take this path for approval of CIPA as a safe and effective drug against dengue and Zika viral infections.

Genetically engineered biomolecules and viral diagnostics
A primary contribution is in the development of novel recombinant designer proteins as inexpensive, highly sensitive and specific diagnostic intermediates for viral infections, such as HCV, HIV and Dengue virus. The availability of high quality diagnostic intermediates for HCV, HIV and HBV from our laboratory to manufacturers of diagnostic kits has reduced production costs significantly. These kits are being manufactured in India and are being used in several Asian and African countries. In collaboration with other academic and industrial collaborators from India and Finland these designer proteins are being explored for developing highly sensitive multiplexed point-of-care assay system for the detection of blood borne infections in medical emergency situations. This Wellcome Trust supported research collaboration aims to produce a new technology concept which upgrades the performance of the currently used rapid-testing methodology with lateral flow assay (LFA) test kits to near PCR sensitivity, but with ease of immune assays. With the new technology infectious diseases can be tested in near-patient conditions with high accuracy and reliability without sacrificing the affordability of the testing.

Recent Publications

Khetarpal, N., Shukla, R., Rajpoot, R.K., Poddar, A., Pal, M., Swaminathan, S., Arora, U., Khanna, N. 2017. Recombinant Dengue Virus 4 Envelope Glycoprotein Virus-Like Particles Derived from Pichia pastoris are Capable of Eliciting Homotypic Domain III-Directed Neutralizing Antibodies. Am J Trop Med Hyg 96,126-134 PubMed link

Poddar, A., Ramasamy, V., Shukla, R., Rajpoot, R.K., Arora, U., Jain, S.K., Swaminathan, S., Khanna, N. 2016. Virus-like particles derived from Pichia pastoris-expressed dengue virus type 1 glycoprotein elicit homotypic virus-neutralizing envelope domain III-directed antibodies. BMC Biotechnol 16, 50 PubMed link

Talha, S.M., Salminen, T., Juntunen, E., Spangar, A., Gurramkonda, C., Vuorinen, T., Khanna, N., Pettersson, K. 2016. Europium nanoparticle-based simple to perform dry-reagent immunoassay for the detection of hepatitis B surface antigen. J Virol Methods 229, 66-69 PubMed link

Sood, R., Raut, R., Tyagi, P., Pareek, P.K., Barman, T.K., Singhal, S., Shirumalla, R.K., Kanoje, V., Subbarayan, R., Rajerethinam, R., Sharma, N., Kanaujia, A., Shukla1, G., Gupta, Y.K., Katiyar, C.K., Bhatnagar, P.K., Upadhyay, D.J., Swaminathan, S., Khanna, N. 2015. Cissampelos pareira Linn: Natural Source of Potent Antiviral Activity against All Four Dengue Virus Serotypes PLoS NTD 28, e0004255. doi: 10.1371/journal.pntd.0004255 eCollection PubMed link

Tripathi, L., Mani, S., Raut, R., Poddar, A., Tyagi, P., Arora, U., de Silva, A., Swaminathan, S., Khanna, N. 2015. Pichia pastoris-expressed dengue 3 envelope-based virus-like particles elicit predominantly domain III-focused high titer neutralizing antibodies. Front Microbiol 6, 1005 PubMed link

Mani, S., Tripathi, L., Raut, R., Tyagi, P., Arora, U., Barman, T., Sood, R., Galav, A., Wahala, W., de Silva, A., Swaminathan, S., Khanna, N. 2013. Pichia pastoris-expressed dengue 2 envelope forms virus-like particles without pre-membrane protein and induces high titer neutralizing antibodies. PLoS One. 8, 5 PubMed link

Patents

N. Khanna and V. Ramasamy. Vaccine. WO 2016/034974 A1

P.K. Bhatnagar, C. K. Katiyar, N. Khanna, D. J. Upadhyay, S. Swaminathan, K. Srinivas, N. Sharma, A. Kanaujia, R. Sood, S. Singhal, G. Shukla, R. Duggar, P. K. Pareek, Y. Singh, S. Khan, and R. Raut. Use of Cissampelos pariera extracts for treating dengue. US 20160243182 A1

P.K. Bhatnagar, C. K. Katiyar, N. Khanna, D. J. Upadhyay, S. Swaminathan, K. Srinivas, N. Sharma, A. Kanaujia, R. Sood, S. Singhal, G. Shukla, R. Duggar, P. K. Pareek, Y. Singh, S. Khan, and R. Raut. Anti-dengue activity of Cissampelos pariera extracts. US 2012/0107424 A1 

P.K. Bhatnagar, C. K. Katiyar, N. Khanna, D. J. Upadhyay, S. Swaminathan, K. Srinivas, N. Sharma, A. Kanaujia, R. Sood, S. Singhal, G. Shukla, R. Duggar, P. K. Pareek, Y. Singh, S. Khan, and R. Raut. Anti-dengue activity of Cissampelos pariera extracts. EP2389184

P.K. Bhatnagar, C. K. Katiyar, N. Khanna, D. J. Upadhyay, S. Swaminathan, K. Srinivas, N. Sharma, A. Kanaujia, R. Sood, S. Singhal, G. Shukla, R. Duggar, P. K. Pareek, Y. Singh, S. Khan, and R. Raut. Anti-dengue activity of Cissampelos pariera extracts. CN102361644 (A)

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