Chit Laa Poh
Sunway University, Malaysia
Title: Rational design of live attenuated Enterovirus 71 vaccine by site-directed mutagenesis and deletion in the 5’-non coding region
Biography
Biography: Chit Laa Poh
Abstract
The hand, foot and mouth disease (HFMD) is commonly caused by Enterovirus 71(EV-A71) and Coxsackieviruses. EV-A71 infection in young children produces fever, rashes and ulcers but some severe infections can lead to encephalitis, cardiopulmonary failure and even death. The lack of vaccines and antiviral drugs against EV-A71 highlights the urgency of developing preventive and treatment agents. The inactivated vaccine (IV) has been approved for production by the regulatory authority in China. Although the efficacy of the EV-A71 sub-genotype C4a vaccine was more than 90% against mild HFMD, there was only 80.4% efficacy against severe HFMD. The IV elicits only humoral immunity but lacks cellular immunity which is required for long term protection. This has necessitated the search for other vaccines such as viral like particles (VLPs) and live attenuated vaccines. In this study, rational design of the live attenuated EV-A71 was undertaken by substituting nucleotides at positions 158, 475, 487, 5262 and creating a 11 base pair deletion in the 5’NTR (PD mutant). Mutants 475, 486 and PD caused minimal cytopathic effects when compared to mutants 158, 486, and 5262 in Rhabdomyosarcoma (RD) cells. This was consistent with the viral RNA copy number and VP1 for mutants 475, 487 and PD being the lowest observed. A desirable live attenuated vaccine strain can be constructed bearing the 11bp deletion and mutation 487.