Could polio vaccines induce cross-reactive antibodies that target SARS-CoV-2?
Among the intriguing aspects of the current pandemic of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is the apparent selectivity of its pathogenicity. Young children are typically spared the severe or life-threatening features of infection, compared to adults over 60 years. A new study led by researchers at Johns Hopkins University, USA, explores a link between immunity to SARS-CoV-2, the earlier SARS-CoV, and childhood poliovirus vaccination. Almost 90% of the worlds people have received this vaccine, but antibodies elicited by it reduce over time and are almost absent at the end of adolescence. A preprint version of the study is available on the medRxiv* server, while the article undergoes peer review. Background  Some earlier studies have shown that certain vaccines have cross-protective efficacy against not just the specific viruses based on which they were created, but on structurally similar viruses too. This is true of the poliovirus vaccine and the mumps vaccine, with one report indicating that the susceptibility to SARS-CoV-2, and COVID-19 severity, are inversely correlated with the titers of mumps antibodies. Both the poliovirus and SARS-CoV-2 contain a single-stranded ribonucleic acid (RNA) molecule as their genetic material, and all proteins are directly translated off this template strand. During viral replication in both, the genome is replicated off this strand, using RNA-dependent-RNA-polymerase (RdRp) protein synthesized. The RdRp enzyme is fundamental in viral replication, and multiple screening attempts have been made to inhibit its activity and thus cripple the virus. The researchers in this study explain, The structural similarities in the RdRp of all single-stranded, positive sense RNA viruses may explain the cross-reactivity of polio-immune serum with SARS-CoV-2 antigens.  Two types of polio vaccines have been used worldwide, one being the oral polio vaccine (OPV) which is a live attenuated vaccine, and the other an inactivated poliovirus vaccine (IPV). Concerns about the potential for reversion to wild-type paralytic poliovirus have led to the cessation of OPV in the USA, where IPV is universally administered. Not only is the latter associated with high efficacy, but it cannot lead to the escape of vaccine-derived-poliovirus (VDPV) into the environment and has few side effects. The researchers intended to test their theory that the age-dependent morbidity and mortality from COVID-19 is mediated by immunity to the virus, which is partly contributed by poliovirus vaccination. Using data from the top 100 countries to be hit by the virus, they found that the higher the median age, the higher the prevalence of the virus was in that country, and the higher the mortality rate from COVID-19. Secondly, they found that the RdRp from SARS-CoV-2 and poliovirus had similar molecular weights of approximately 130 kD, with similar tertiary and quaternary structures. Both were bound at one site, at least, by the mouse anti-RdRp monoclonal antibody 4E6. The researchers found anti-RdRp antibodies in a sample of both adults and children, which were able to recognize the RdRp of both viruses. Higher titers were seen in those who had received IPV. Immune serum from these individuals inhibited viral replication in Vero cells, with stronger effects being observed when the antisera were added to the cells before viral challenge. The strongest inhibition was seen with antisera from fully immunized young children and from young adults. If poliovirus immunization builds immunity to the novel coronavirus, these results are expected since, by one year of age, the child would have been fully immunized but not at four months. The same effect is seen when an adult is immunized with two doses of IPV, inducing stronger inhibition of SARS-CoV-2-induced cytopathic effects (CPE) in the cell culture. Protection from either polio or SARS-CoV-2 declines with age, but inhibition of CPE improves by over a third with a single IPV booster dose. Lower immunity in adults aged 60-65 years may be partially compensated for by IPV, raising the immunity above that of an adolescent who was not recently immunized. In vitro inhibition of RdRp activity was observed with poliovirus antisera randomly selected from immunized adults and children, with 13 of 17 samples showing effective inhibition of RdRp enzymatic activity. The study shows that poliovirus vaccination raises antibodies that cross-react with SARS-CoV-2, with the primary target of these antibodies being the RdRp of poliovirus and coronavirus. Antisera from immunized individuals prevent SARS-CoV-2 CPE in cell cultures. The antisera successfully reduced RNA replication by inhibiting RdRp activity. These findings may imply that childhood vaccinations elicited antibodies to SARS-CoV-2 in younger individuals and thus reduced their susceptibility to the virus. This harmonizes with studies that indicate a possible role for the anti-tuberculosis BCG, MMR (targeting measles, mumps and rubella) and poliovirus vaccines in protecting against SARS-CoV-2 infection. The study also draws attention to the potential importance of RdRp as a therapeutic target. Anti-RdRp antibodies apparently inhibit SARS-CoV-2 CPE by preventing its adsorption or internalization into the host cell, mediated by viral genome-RdRp interactions. Thus, other SARS-CoV-2 protein antigens than the immunodominant spike may be suitable for vaccine development. We suggest IPV immunization may induce adaptive, generally long-term, and specific immunity to poliovirus and SARS-CoV-2 infection. The authors are continuing their investigation via a larger clinical trial to test the usefulness of this vaccine in the prevention of COVID-19. The possibilities are bright, as the poliovirus vaccine is a decades-old vaccine with abundant safety data, and established pharmacological standards. Manufacturing and toxicity data are also readily available. In the light of significant vaccine hesitancy directed at the newly developed COVID-19 vaccines and the shortfall in vaccine supplies, the researchers suggest that the utility of the poliovirus vaccine be re-examined in this light. *Important notice  medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.