Development of a Modified mRNA-Based Vaccine for Lassa Virus

ABSTRACT

Lassa virus (LASV) is a highly prevalent pathogen in West Africa, including Sierra Leone, Liberia, Guinea and Nigeria. The virus causes 100,000 to 300,000 infections per year, which lead to approximately 5,000 deaths annually. Lassa fever is currently on the WHO R and D Blueprint list of epidemic threats needing urgent R and D action, and therefore there is an unmet need for an effective LASV vaccine, especially one that prevents Service Members from becoming ill from epidemic disease exposure during operational deployments. The innovative vaccine technology used in this funded project was developed based on mRNA modified by incorporation of pseudouridin, which dramatically minimizes the indiscriminate activation of innate immune sensing and increases translation by an order of magnitude. This revolutionary technology was used by Moderna Therapeutics, the partner in this project, for the development of highly effective vaccines against influenza virus, rabies, HIV, Zika virus and SARS-CoV-2;the influenza and SARS-CoV-2 vaccines have been tested recently in clinical trials. Dr. Bukreyev and Moderna have designed and tested two Ebola virus modified mRNA-based vaccines encapsulated in lipid nanoparticles (LNP), which induced neutralizing antibodies in immunized guinea pigs and completely prevented death and disease caused by Ebola virus challenge