Multiple variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have emerged rapidly since the first identification of the virus in Wuhan, China, in late December 2019. The current variants of SARS-CoV-2 categorized as a variant of concern (VOC) include the Alpha, Beta, Gamma, and Delta variants. Currently, the Delta variant is of concern due to its worldwide spread.
The primary target for most therapeutic methods against Coronavirus disease 2019 (COVID-19) was the spike (S) protein of SARS-CoV-2. Two of the most common methods involve the use of monoclonal antibodies (mAb) that are targeted towards the Receptor Binding Domain (RBD) and the N-terminal domain (NTD) of the spike protein, and polyclonal antibodies obtained from convalescent plasma therapy (CP) of SARS-CoV-2 survivors that contains antibodies to multiple epitopes of the S protein.
However, mutations in the S protein of such variants, as previously mentioned, have been demonstrated to reduce or eradicate the efficacy of commonly used therapeutics.
A study, available on the pre-print server bioRxiv*, evaluated the neutralizing capacity of a fully human polyclonal antibody (SAB-185) against the Delta, Kappa, and Lambda variants using a lentiviral-based pseudovirus assay.
*Important notice: bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.
What did the study involve?
The study involved producing a fully human polyclonal antibody (SAB-185) from the plasma of Transchromosomic bovines (Tc bovines) that has been hyperimmunized by the SARS-CoV-2 strain every 21 to 28 days for rapid production of SAB-185.
Subsequently, a neutralization assay involving a cell line expressing ACE2 and Transmembrane Serine Protease was performed, which helps determine the antibody products' half-maximal inhibitory concentration (IC50) ratio against the new SARS-CoV-2 variants compared to the ancestral strain.
What did the study show?
The results showed that the SAB-185 retained potency against the different strains of SARS-CoV-2 in vitro and did not develop escape mutants, which was seen in the case of monoclonal antibody convalescent plasma therapy. Using a pseudovirus system presents benefits over screening wild-type SARS-CoV-2 variants, namely safety, genetic stability, and scalability for screening assays.
Significantly, this study presents a framework for how future variants of concern could be promptly and rapidly assessed as they are identified. Furthermore, this same framework could be applied to future pandemics or other pathogens with high mutation rates.
SAB-185
SAB-185 is a fully-human polyclonal antibody therapeutic in a Phase 2/3 adaptive trial for the treatment of COVID-19. It was developed in collaboration with the US government using SAB Biotherapeutic’s novel proprietary DiversitAb Rapid Response Antibody Program. In preclinical studies, the novel therapeutic has shown potent neutralization of the Munich, Washington and other variant strains, including Delta and Lambda. Preclinical data has also indicated that SAB-185 is significantly more potent than human-derived convalescent immunoglobulin G (IgG).
*Important notice: bioRxiv 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.
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