Harnessing The Power of High-throughput Human Monoclonal Antibodies for Rational Design and Development of Dengue Envelope Immunogens Using Reverse Vaccinology 2.0
Description: Our main research question is: Can we design and develop an effective native-like pre-fusion state dengue viral dimeric envelope E-protein based immunogen vaccine utilizing a combination of cutting edge technologies - high-throughput human monoclonal antibodies generation technology and reverse vaccinology 2.0. A major goal of dengue virus (DENV) vaccine is to induce pan-neutralizing antibodies (pnAbs), without eliciting antibodies that are non-neutralizing and potentially enhancing infectivity with antibody dependent enhancement (ADE) activity. To achieve this, an insight of the pnAbs response to DENV during natural infection is required. In virtually all infections, select individuals are able to develop highly potent pnAbs responses, thus serve as potential donors for isolation of pnAbs, which will contribute towards structure-guided immunogen design. For this, we will make human DENV pnAbs from memory B cells derived from individuals that have multi-serotype neutralizing antibody responses that we will then use for the reverse vaccinology 2.0 approach to design and develop effective native-like DENV dimeric E-protein envelope based immunugens.This study will not only result in production of DENV pnAbs that can potentially be exploited for mAbs based therapeutics for DENV infections, but also development of novel vaccine candidates that results in eliciting DENV pnAbs without ADE in-vivo.
Amount: INR 16,880,000
Funding type: fellowship
Funder scheme: Early Career Fellowship
Start date: 2020-01-01
End date: 2024-12-31
Investigators: Sanjeev Kumar, Sanjeev Kumar
Institution: International Centre for Genetic Engineering and Biotechnology
Funded outputs count: 15
Funder award ID: IA/E/18/1/504307
OpenAlex ID: G4365637370