Developing Recombinant MRNA Vaccine for Nipah Virus by Fusion Protein(mammalian&viral glycoproteins)

April 30, 2024 Colloquia Presenters

Department of Biological, Human & Life Sciences

Designing and developing a recombinant mRNA vaccine against the Nipah virus (NiV) by targeting fusion protein binding between mammalian and viral glycoproteins

The Nipah Virus (NiV) is a single-strand antisense RNA virus that relies on the specific binding of receptor proteins to increase its transendothelial migration across mammalian cells. The binding mechanism of NiV attachment protein G with EphrinB2 and Ephrin B3 activates F-mediated fusion, resulting in infection of the cell. However, current limitations in drug discovery efforts against NiV focus on the use of Remdesivir and Ribavirin and need to take into account the virus's innate ability to mutate, consequently rendering most organic small molecule approaches ineffective as long-term prophylactic agents. Here, we show the potential usefulness of a messenger RNA (mRNA) vaccine library as a stand-alone or combinatorial therapeutic agent along with FDA-approved drugs. Using in silico and in vitro models, recombinant NiV vaccine libraries were synthesized to replicate mutated receptor attachment glycoproteins. By using a codon optimization model, we evolve the NiV attachment proteins in an evolutionary congruent fashion. These candidate mRNA vaccines were encapsulated in lipid nanoparticles (LNPs) and transfected into mammalian cells to assess the efficiency of transfection and viability of the vaccine. Our early-stage mRNA vaccine library presents great potential since it is well-substantiated that these glycoproteins are required for viral entry. Similar to SARS-CoV-2, NiV exhibits rapid community transmission, however, with a higher mortality rate of 40-75%. This study proposes the effectiveness of a highly scalable and potentially low-cost mRNA vaccine library to circumvent the consequences of a NiV outbreak.

RESEARCHERS: Rajesh V., Saint Francis High School '24, Caleb Y., Saratoga High School '25, Anishka D. Basis Independent Silicon Valley '25, Shreya R. Monta Vista High School '25, Erin L., Irvington High School '25

ADVISOR: Amadi Lab Biotechnology and Synthetic biology

KEYWORDS: Biotechnology | Vaccine Development | Codon Optimization