Inactivated Poliovirus Vaccine Induces Antibodies that Inhibit RNA Synthesis of SARS-CoV-2: An open-label, pre-post vaccine clinical trial
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Abstract
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-3D pol (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-3D pol 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 .
Article activity feed
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SciScore for 10.1101/2021.10.05.21264598: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics Consent: IRB approval (Advarra IRB) was obtained for the study protocol, informed consent forms, recruitment materials, and all subject-facing materials. Sex as a biological variable not detected. Randomization Fifty-four of the 298 post-inoculation serum samples were randomly selected to be tested with the RdRp polymerase assay, due to the expensive nature of immune-based detection methods. Blinding not detected. Power Analysis not detected. Table 2: Resources
Antibodies Sentences Resources Exclusion criteria included: known allergic reactions to components of the poliovirus vaccine, febrile illness within 14 days, positive test result for SARS-CoV-2 antigenemia at any time prior to screening, … SciScore for 10.1101/2021.10.05.21264598: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics Consent: IRB approval (Advarra IRB) was obtained for the study protocol, informed consent forms, recruitment materials, and all subject-facing materials. Sex as a biological variable not detected. Randomization Fifty-four of the 298 post-inoculation serum samples were randomly selected to be tested with the RdRp polymerase assay, due to the expensive nature of immune-based detection methods. Blinding not detected. Power Analysis not detected. Table 2: Resources
Antibodies Sentences Resources Exclusion criteria included: known allergic reactions to components of the poliovirus vaccine, febrile illness within 14 days, positive test result for SARS-CoV-2 antigenemia at any time prior to screening, positive test result for SARS-CoV-2 antibodies at any time prior to screening, treatment with an investigational drug or other intervention within 90 days prior to enrollment in the study, inoculation with poliovirus vaccine within the last 12 years, any symptoms related to SARS-CoV-2 infection (fever or chills, cough, shortness of breath, fatigue, muscle or body aches, headache, new loss of taste or smell, sore throat, congestion, runny rose, nausea, vomiting, diarrhea) within 48 hours, and women who are pregnant or breast-feeding. SARS-CoV-2suggested: NoneAt the second on-site visit (28 ± 3 days post-inoculation), additional blood specimens were collected and tested for IPV-induced poliovirus antibodies including RdRp, hereafter called “anti-3Dpol (RdRp) antibodies,” as well as potential inhibition of SARS-CoV-2 RNA synthesis via impeding RdRp enzymatic activity. RdRpsuggested: NoneAntigen-specific antibodies in the serum sample then bound to the wells, and unbound antibodies were washed out with PBS-T buffer. Antigen-specificsuggested: NoneNext, a solution of horseradish perodixase (HRP) conjugated goat anti-human IgG/A/M secondary antibody was added against the human antibodies to each of the wells. anti-human IgG/A/Msuggested: NoneSoftware and Algorithms Sentences Resources An ELISA plate reader was used to record the activity and raw data were analyzed on Microsoft Excel. Microsoft Excelsuggested: (Microsoft Excel, RRID:SCR_016137)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Since this clinical trial was the first study of its kind to evaluate IPV in the context of the COVID-19 pandemic, the study design was intentionally simple as a single arm, open-label study, and thus includes inherent limitations that should also be considered opportunities for future studies. As a single-site study, the sample size, geographic representation, and demographics were limited. While the studied cohort as a whole was representative of the local San Diego population, Asian and Hispanic/Latino subgroups were slightly underrepresented. In response, future studies may conduct a larger trial, both in terms of size and through a multi-centered approach, in order to enhance generalizability across different populations. There are already active follow-up serological studies focused on stratifying immunological responses across different ages and racial/ethnic groups, but future studies may expand the current understanding of varying immune responses in more diverse settings. In addition to expanding in size, future trials may also incorporate more complex design features to build upon this preliminary study. A multi-armed approach could be used to compare populations of varying vaccination statuses, such as COVID-19 vaccine only, IPV only, COVID-19 vaccine and IPV, and placebo. In this study, enrolled participants had not received any prior COVID-19 immunizations, though if they wanted to get vaccinated, they could do so after their second on-site visit. Future studies...
Results from TrialIdentifier: We found the following clinical trial numbers in your paper:
Identifier Status Title NCT04639375 Active, not recruiting Polio Vaccine (IPV) for SARS-CoV-2 and Prevention of Coronav… Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
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