Inactivated Poliovirus Vaccine Induces Antibodies that Inhibit RNA Synthesis of SARS-CoV-2: An open-label, pre-post vaccine clinical trial

Comunale, B. A.; Jackson-Ward, E.; Jiang, Y.; Ward, L. P.; Liu, Q.; Ji, L.; Lai, M.; Comunale, R. A.; Engineer, L.; Xie, Q.

Background: Poliovirus vaccination induces an adaptive humoral immune response; in vitro experiments show polio-immune sera contain antibodies against the poliovirus RNA transcriptase that cross-react with SARS-CoV-2. While structural similarities between poliovirus and SARS-CoV-2 could have major implications for the COVID-19 response worldwide, polio-induced immune responses against SARS-CoV-2 have not been confirmed in prospective clinical trials. Objective: To evaluate whether immune sera from adults who recently received inactivated poliovirus vaccination (IPV) can block SARS-CoV-2's ability to synthesize RNA. Intervention: IPV intramuscular injection. Measurements: Pre-inoculation and 4-weeks post-inoculation sera were tested for anti-3Dpol (RNA-dependent RNA polymerase, RdRp) antibodies using enzyme-linked immunosorbent assays (ELISA). To assess IPV's ability to induce antibodies that inhibit SARS-CoV-2 RNA synthesis, immune-based detection assays tested RdRp enzymatic activity in polio-immune sera. Results: 298 of the 300 enrolled participants completed both on-site visits. Comparing pre-inoculation to 4-week samples, 85.2% of participants demonstrated an increase in anti-3Dpol antibodies against RdRp proteins. Among tested post-inoculation samples, 94.4% demonstrated inhibition of SARS-CoV-2 RNA synthesis. Few inoculation-related side effects were reported (2.0%), all were minor. Limitations: Participants were not systematically tested for COVID-19, though known exposures were reported and positive results (1.7%) were documented. Conclusion: IPV can induce antibodies that inhibit SARS-CoV-2 RNA synthesis, minimizing the risk of viral replication in infected individuals. This finding has practical implications for resource-deficient areas that may have limited access to newly developed COVID-19 vaccines and/or areas with low COVID-19 vaccination rates due to hesitancy. Funding Source: Private donors. Registration: ClinicalTrials.gov: NCT04639375.