Life Sciences & Biotechnology
Title : | Structure-guided enhancement of capsid stability of foot-and-mouth disease virus serotype O Indian vaccine strain |
Area of research : | Life Sciences & Biotechnology |
Focus area : | Virology & Structural Biology |
Principal Investigator : | Dr. Suresh H Basagoudanavar, ICAR- Indian Veterinary Research Institute (ICAR-IVRI), Izatnagar, Uttar Pradesh |
Timeline Start Year : | 2023 |
Timeline End Year : | 2026 |
Contact info : | surbh2001@gmail.com |
Details
Executive Summary : | Foot and mouth disease (FMD) is a contagious viral disease of cloven-hoofed animals. The disease is endemic in India with prevalence of serotypes O, A and Asia-1. Vaccination is the effective way to control FMD. Animals are currently immunized with inactivated virus vaccine to control the disease; however, the efficacy of the vaccine is dependent on cold-chain maintenance due to its short shelf life. To address this, there is a need to develop new generation vaccine with stable capsids to induce robust and long-term immunity. This study aims to carryout cryo-electron microscopy (Cryo-EM) based structural analyses of the viral capsids of FMDV serotype O which is relatively less stable than the serotype Asia 1. The three-dimensional structure of serotype O viral capsids in comparison with that of Asia 1 will provide knowledge to rationally engineer capsids of serotype O virus for enhancing its stability, for providing enhanced and long duration of immunity. It is also expected that dependence on cold storage of the vaccine will be minimal, thus making it suitable for mass immunization program. Objectives: (1) To determine comparative high-resolution cryo-electron microscopy structures of purified FMDV capsids of serotype Asia1 and O (2) To generate full-length infectious cDNA clone of FMDV serotype O IND/R2/75 introducing mutations that potentially enhance capsid stability (3) To evaluate vaccine stability of rescued recombinant FMDV serotype O IND/R2/75 in guinea pig model Hypothesis: Establishing the structural basis of the FMDV viral capsids by Cryo-EM, which allows us to visualize single viruses, will provide knowledge base to generate a stable FMDV serotype O vaccine candidate. The vaccine strain with more stable capsid structure will enhance the duration of immunity in vaccinated animals besides minimizing dependence on cold storage of the vaccine, making it suitable for mass immunization program. Main experiments: High resolution cryo-EM and three-dimensional image reconstruction will be carried out to identify the molecular differences and types of interactions at the inter-pentameric regions of the capsids of FMDV serotype Asia1 (relatively stable) and serotype O (less stable). Using the structure guided data, desired mutations in the capsid coding protein(s) of FMDV serotype O IND/ R2/75 will be introduced using reverse genetics approach. The enhancement of the virus capsid stability will be characterized by thermal inactivation and Thermo PaSTRy assay. The proof of concept for the efficacy of the enhanced vaccine capsid stability will be evaluated by immunization study in guinea pigs. Significance to the field of research: The use of FMDV serotype O vaccine strain IND/R2/75 with enhanced capsid stability could offer a significant improvement in the control of FMD in Indian sub-continent. It could also potentially induce long duration immunity, making it suitable for mass FMD immunization. |
Co-PI: | Dr. Madhusudan Hosamani, ICAR- Indian Veterinary Research Institute (ICAR-IVRI), Izatnagar, Uttar Pradesh-560024, Dr. Sreenivasa B.P., ICAR- Indian Veterinary Research Institute (ICAR-IVRI), Izatnagar, Uttar Pradesh-560024 |
Total Budget (INR): | 44,96,420 |
Organizations involved