POLIOVIRUS VACCINATION IN THE CONTEXT OF THE 
COVID-19 PANDEMIC: AN EXPLORATION OF WHETHER AN ESTABLISHED VACCINE COULD HAVE VALUE IN FIGHTING A NEW AND EVOLVING VIRUS, AND THE IMPACT OF BIOLOGICAL AND SOCIAL FACTORS ON THIS STRATEGY

Embargo until
2027-08-01
Date
2023-07-17
Journal Title
Journal ISSN
Volume Title
Publisher
Johns Hopkins University
Abstract
Theory: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19), emerged in 2019, rapidly spread across the globe, and continues to be transmitted today. Vaccination is the primary measure available for preventing infection and reducing severity of disease, however because currently available COVID-19 vaccines all target the virus' spike protein, which can evolve from one variant strain to the next, their efficacy can quickly wane. In order to stay ahead of future variants, researchers have sought to identify prophylactic agents (i.e., drugs and vaccines) that target proteins that are more highly conserved, less mutable. In addition, because proteins are often shared across similar RNA viruses, there is interest in whether drugs and vaccines developed for other RNA viruses could be effective against SARS-CoV-2. To help address these questions, using the well-established poliovirus vaccine as an example, this dissertation examines whether existing agents that target the highly conserved RNA-dependent RNA polymerase (RdRp) protein, could be repurposed to prevent and treat SARS-CoV-2, and how biological and social factors might impact such a strategy. Methods: The first manuscript presents a scoping review of the functional implications of RdRp in the context of the COVID-19 pandemic. Studies examining if and how existing drugs and compounds inhibit SARS-CoV-2 RdRp activity are summarized. The second manuscript examines vaccination histories of adults recently inoculated with the inactivated poliovirus vaccine (IPV) and the potential impact on SARS-CoV-2 infection and COVID-19 symptoms. The third manuscript further explores this study population, focusing on risk factors related to biological and social determinants of health. Results: The scoping review indicates that existing drugs and compounds that target the RdRp protein can not only disrupt SARS-CoV-2 replication of the original “Alpha” strain, but also subsequent variants. These findings validate the idea that agents targeting highly conserved proteins can be effective regardless of which variant is circulating, and suggest that drugs initially developed for a different RNA virus could have value when repurposed against SARS-CoV-2. Analyses of survey data from adults recently vaccinated with the inactivated poliovirus vaccine (IPV) reveal underlying medical conditions, employment status, vitamin D supplementation, and education level may impact subsequent COVID-19 outcomes. Additionally, regression models adjusted for vaccination histories as well as biological and social determinants of health show that oral poliovirus vaccination (OPV) is associated with a significantly lower incidence of SARS-CoV-2 infection and a shorter duration of COVID-19 symptoms. Conclusions: Prophylactic and therapeutic agents that target RdRp may complement current COVID-19 prevention and treatment tools. Clinical trial survey data support studies that suggest IPV can boost mucosal immunity in OPV primed individuals. Future, larger-scale studies are recommended.
Description
Keywords
NSP12 Protein, SARS-CoV-2, Drug Repurposing, COVID-19, Mucosal Immunity, Primary Prevention, Vaccines, Immunology, Social Determinants of Health
Citation