SARS-CoV-2 Antibody Cross-Reactivity and Neutralization Property
A range of SARS-CoV specific antibodies have shown cross-reactivity with SARS-CoV-2. These antibodies target S protein and mostly the RBD region (Hoffmann et al., 2020). Monoclonal antibodies against SARS-CoV such as CR3022 and S309 have shown cross-reactivity with SARS-CoV-2 (Pinto et al., 2020; Wang et al., 2020a). Similarly, in a study of 285 patients, S protein-specific antibodies from SARS-CoV showed cross-reactivity with CoV-2 N protein in a subset of patients (n = 5), whereas no-cross reactivity was detected against S1 subunit of SARS-CoV-2 (Long et al., 2020a). Thus, the cross-reactive nature of some of these antibodies may ensure their efficacy against multiple coronaviruses.
However, at the same time, these cross-reactive antibodies should also have neutralizing property; otherwise, they will have a harmful effect. A recent study explored the cross-reactive and neutralization property of these antibodies simultaneously (Lv et al., 2020). This study used plasma from 15 SARS-CoV-2 and 7 SARS-CoV patients and found a high degree of cross-reactivity between the antibody response from these samples, but a very low antibody neutralizing property. These results were further confirmed in animal models of SARS-CoV-2 and SARS-CoV. While S309 antibody showed better neutralization property against SARS-CoV-2, the neutralization properties for CR3022 are not yet known (Pinto et al., 2020; Wang et al., 2020a). Thus, although a high degree of cross-reactivity of the antibody response from SARS-CoV-2 can be found with other related CoVs, the neutralizing property of these antibodies may be epitope specific. The weak neutralizing property of such cross-reactive antibodies should thoroughly be tested before usage as a therapeutic intervention, to prevent the complications which may arise due to antibody-dependent enhancement (ADE). These factors also become essential while considering convalescent plasma therapy.
In an elegant recent study, Cao et al. (2020) performed sc-RNA-seq of B cells from 60 convalescent COVID-19 patients. The study led to the identification of 14 neutralizing antibodies, among which one (BD-368-2) showed the most potent effect. BD-368-2 was further explored for its efficacy in animal models and showed therapeutic potential in SARS-CoV-2 transgenic animals. Further, the study suggested the use of two different monoclonal antibodies targeting different epitopes as a more viable therapeutic intervention than a single antibody, which is impressive considering the emerging mutations in SARS-CoV-2. Thus, more research in this direction is needed to find antibodies with potent neutralization property for targeted therapy to alleviate the disease burden.