Monoclonal antibodies as therapeutics and diagnostics for CHIKV infection
Implementing Organization
National Institute of Immunology (NII)
Principal Investigator
Mr. PRAKHAR AGRAWAL
National Institute Of Immunology
prakharagrawal@nii.ac.in
Project Overview
An increase in human and wildlife conflict has led to the rise in cross-species transmission of diseases, specifically zoonotic diseases. This problem has further escalated with changes in climatic conditions, a decrease in pathogen specificity for their host, and changes in human susceptibility/ immunity to communicable diseases. This problem has worsened due to rapid population growth, increased global travel, inadequate surveillance, and limitations imposed by traditional diagnostic measures. Furthermore, the complex interplay between the pathogen's ability to adapt, the frequency and nature of interactions between different species, and environmental conditions that facilitate transmission advocates for newer methods for tackling increased disease burden.
Among different zoonotic diseases wreaking havoc, Chikungunya virus (CHIKV) has spread across various continents like Asia, Africa, and Europe, with millions of people getting infected every year in more than 100 countries. The rapidly changing climatic conditions and the global distribution of mosquito vectors have increased the likelihood of its spread in previously unaffected areas, specifically in tropical countries. Furthermore, it's spread to places with no drugs or vaccines poses significant public health issues. Hence, it warrants the need to develop anti-CHIKV therapeutics. Previous studies have attempted to target various structural and non-structural proteins of CHIKV using small molecules. However, these approaches have several disadvantages, such as non-specificity, low efficacy, and potential side effects. Hence, to overcome these problems, we propose to develop monoclonal antibodies (mAbs) as a potential alternative for treating CHIKV infection. In this proposal, we aim to produce mAbs that specifically target the E2 protein of CHIKV, which is conserved within alphaviruses and plays a vital role in receptor and antibody binding. Along with its therapeutic use, mAbs thereby produced will also be tested for diagnostic purposes to overcome the observed cross-reactivity in detection with other viruses, especially the Dengue virus. Further, the mAbs produced will be validated using in vitro and in vivo studies by evaluating the efficacy and viral load reduction upon infection.
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