In a recent study posted to the bioRxiv* pre-print server, a team of researchers discussed the efficacy of ABP-310, a neutralizing antibody (nAb), against all tested severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, including Omicron.
Study: A potent SARS-CoV-2 neutralizing antibody recognizing a conserved epitope with broad mutant variant and SARS-CoV activity. Image Credit: Design_Cells/Shutterstock
Although nAbs have shown great promise in the treatment of coronavirus disease 2019 (COVID-19), the emergence of SARS-CoV-2 mutant variants (such as Omicron) resistant to nAb therapy is a major concern. To combat this issue, the nAbs that recognize conserved epitopes of SARS-CoV-2, shared by other coronaviruses, could prove to be very helpful.
*Important notice: bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.
Currently, only sotrovimab nAb uses this conserved epitope approach. Considering their huge potential as antiviral therapeutics, the US National Institutes of Health has recommended that such broadly acting nAbs be stockpiled for future use.
About the study
In the present study, researchers developed a novel nAb therapeutic approach using an antibody, ABP-310, derived from B cells of a convalescent COVID-19 patient.
All therapeutic SARS-CoV-2 nAbs prevent the receptor-binding domain (RBD) of SARS-CoV-2 spike (S) protein from binding to human angiotensin-converting enzyme (hACE2), a host cell receptor that facilitates viral entry. The researchers used an in vitro ACE2 competition assay to demonstrate the ability of ABP-310 to block the ACE-2-RBD interaction.
They also specifically assessed the ability of ABP-310 to bind SARS-CoV-2 S protein domains bearing a variety of mutations, such as N234Q, K417N, N440K, K444R, L452R, E484K, F490L, S494P, and D614G. The lentiviruses were pseudotyped with SARS-CoV-2 S proteins, including the Wuhan isolate, all the identified variants of concern (Alpha, Beta Gamma, Delta, and Omicron), and major variants of interest (Epsilon, Eta, Iota). Additionally, they tested its ability to bind the S1 domain of the S proteins from Middle East respiratory syndrome-related coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus (SARS-CoV). The researchers also examined the neutralization activity of all the assayed nAbs.
As comparator controls, they used the expressed sequences of other nAbs already in use as therapeutics, such as casirivimab, imdevimab, and sotrovimab.
Findings
All the examined antibodies displayed strong binding activity against all SARS-CoV-2 mutants tested; however, the authors observed a marked reduction in the binding of casirivimab to the Beta variant. Further, only sotrovimab, a nAb derived from a memory B cell screen of a patient infected with SARS-CoV during the 2003 epidemic, displayed binding to either SARS-CoV or MERS-CoV.
The authors identified ABP-310, a nAb, with potent neutralizing activity against all the currently circulating SARS-CoV-2 variants of concern, including Omicron. ABP-310 exhibited the ability to bind a conserved epitope and neutralize a related coronavirus, SARS-CoV, but not MERS-CoV.
The results demonstrated the broad neutralizing activity of ABP-310 against all the circulating variants of SARS-CoV-2, including Omicron. In addition, this nAb exhibited conserved epitope binding for neutralization of a related betacoronavirus (SARS-CoV), therefore, it is possible that ABP-310 may be able to neutralize future SARS-CoV-2 variants and other yet unknown novel beta coronaviruses, as well. While casirivimab also displayed detectable neutralization against SARS-CoV, it was approximately 500-fold weaker in potency compared to ABP-310.
Unlike sotrovimab, another nAb showing potent neutralizing activity against all SARS-CoV-2 variants and SARS-CoV, ABP-310 showed a mean 10.3-fold greater potency against SARS-CoV-2 variants and 2.1-fold greater potency against SARS-CoV. Intriguingly, both ABP-310 and sotrovimab were able to neutralize the Omicron variant, with ABP-310 being 2.5-fold more potent than sotrovimab. Other tested nAbs, such as casirivimab and imdevimab, failed against Omicron and displayed little or no activity against SARS-CoV.
Conclusions
Currently, emergency use authorization (EUA) by the U.S. Food and Drug Administration (FDA) has been given to monoclonal nAbs or nAb cocktails from Regeneron, Lilly, and GSK/Vir. However, four of them, including casirivimab, imdevimab, bamlanivimab, and estevimab, failed to neutralize the SARS-CoV-2 Omicron variant which leaves only one nAb, sotrovimab, as showing neutralizing activity against Omicron. Thus, the study findings highlight the urgent need for the development of SARS-CoV-2 nAb-based therapeutics that are more resistant to mutant escape.
To conclude, ABP-310 nAb showed potent neutralizing activity against all SARS-CoV-2 variants tested, including Omicron. Hence, ABP-310 may potentially be an effective antibody therapy for treatment or prophylaxis of SARS-CoV-2 infection. Additionally, given the conserved nature of its epitope binding and its cross-species viral neutralization, ABP-310 may also serve as an early therapeutic intervention during a future pandemic.
*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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