Development of a Pan-COVID-19 Vaccine Candidate

ABSTRACT The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2), has impacted global public health in an unprecedented manner. Vaccination is considered one of the most effective countermeasures against infectious diseases, including COVID-19. Although rapid development of first-generation COVID-19 vaccines (principally targeting the viral Spike protein) provided early hope for ending the pandemic, the emergence of SARS-CoV-2 variants has posed a constant challenge. A pan-COVID- 19 vaccine that provides broad protection against current and emerging variants is urgently needed to end the pandemic and to prevent future recurrences. mRNA formulated in lipid-nanoparticles (mRNA-LNP) has emerged as a safe and versatile vaccine delivery platform. RNA Therapeutics, Inc. is a startup biotechnology company focused on the development of novel, mRNA-based vaccines and therapeutics for infectious diseases. Its academic partner, Dr. Haitao Hu’s laboratory at the University of Texas Medical Branch (UTMB), recently reported a promising pan-COVID-19 mRNA vaccine candidate (Hajnik RL, STM 2022). The Hu laboratory generated an mRNA vaccine expressing the nucleocapsid protein (N) of the ancestral SARS-CoV-2 strain, which is more conserved among variants (termed as mRNA-N). Animal studies showed that mRNA-N is highly immunogenic and elicits strong T-cell and binding antibody responses. The vaccine alone confers modest cross protection against SARS-CoV-2 Delta and Omicron variants of concern (VOC). Interestingly, combining mRNA-N with the clinically proven ancestral spike mRNA vaccine (mRNA-S) induces robust cross protection against both Delta and Omicron VOCs (mRNA-S+N). These data support a hypothesis that a vaccine approach targeting conserved viral protein, in addition to S, will elicit cross- reactive immunity and provide broad protection against SARS-CoV-2 variants. With this technology in hand, RNA Therapeutics, Inc. and UTMB propose a Phase-I STTR application to further develop the mRNA vaccine candidate through two specific Aims. Aim 1 will examine the durability of protective efficacy of the vaccine in hamsters. Aim 2 will determine protective efficacy of mRNA-N as a component of booster regimens. Impact: Upon successful completion of this Phase-I STTR, we will submit a Phase-II application that will focus on advanced product development. Our project is expected to develop a pan-COVID- 19 mRNA vaccine that provides broad protection against emerging SARS-CoV-2 variants and the long-term goal is to advance this vaccine to clinical testing and approval. Given the proven safety of mRNA-LNP, the vaccine has high potential to be approved for human use in future.