Two linear epitopes on the SARS-CoV-2 spike protein that elicit neutralising antibodies in COVID-19 patients

Abstract

Given the ongoing SARS-CoV-2 pandemic, identification of immunogenic targets against the coronavirus spike glycoprotein will provide crucial advances towards the development of sensitive diagnostic tools and potential vaccine candidate targets. In this study, using pools of overlapping linear B-cell peptides, we report two IgG immunodominant regions on SARS-CoV-2 spike glycoprotein that are recognised by sera from COVID-19 convalescent patients. Notably, one is specific to SARS-CoV-2, which is located in close proximity to the receptor binding domain. The other region, which is localised at the fusion peptide, could potentially function as a pan-SARS target. Functionally, antibody depletion assays demonstrate that antibodies targeting these immunodominant regions significantly alter virus neutralisation capacities. Taken together, identification and validation of these neutralising B-cell epitopes will provide insights towards the design of diagnostics and vaccine candidates against this high priority coronavirus.

Antigenic variation of SARS-CoV-2 in response to immune pressure

“…Overall, these data fit very well with the observation that most humoral immune responses against SARS-CoV-2 and other human coronaviruses are directed against the S and N proteins (Farrera et al, 2020;Jiang et al, 2020;Poh et al, 2020). These results also support the notion that the selective pressure exerted by the human antibody response is already detectable in the SARS-CoV-2 population.…”

“…Specifically, because they are the major targets of the humoral immune response (Channappanavar et al, 2014;St John and Rathore, 2020;Vabret et al, 2020), we predicted both linear and conformational B epitopes for the S and N proteins, whereas only linear epitopes were predicted for the other viral proteins (Table S1). A good correspondence was observed between B cell epitope predictions for the S protein and epitopes identified in two works that systematically mapped antibody responses in the sera of convalescent COVID-19 patients (Farrera et al, 2020;Poh et al, 2020) (Figure 1).…”

“…These works, as well as others (Farrera et al, 2020;Poh et al, 2020), revealed that the cell-mediated responses against SARS-CoV-2 are not restricted to the nucleocapsid (N) and spike (S) proteins, but rather target both structural and non-structural viral products. In parallel, analyses of B cell responses in SARS-CoV-2 infected patients showed that the S and N proteins are the major target of the antibody response and identified specific B cell epitopes in the S protein (Farrera et al, 2020;Jiang et al, 2020;Poh et al, 2020). We exploited this growing wealth of information to investigate whether, after a few months of sustained transmission, the selective pressure exerted by the human adaptive immune response is already detectable in the SARS-CoV-2 population and to investigate how the virus is evolving in response to such a pressure.…”

“…An in house R script was written and is available as supplementary text S1. (Farrera et al, 2020;Poh et al, 2020) are also reported in red.…”

Epitope-resolved profiling of the SARS-CoV-2 antibody response identifies cross-reactivity with an endemic human CoV

“…In its simplest format, peptides can be used individually, for example in separate wells in an ELISA. A recent study used this approach to identify two linear epitopes in S protein that were targeted by neutralizing antibodies in SARS-CoV-2 convalescent donors (Poh et al, 2020). More powerful assays involve sets of peptides that are assayed in multiplex -using either spatial addressing, in the case of peptide arrays (Price et al, 2012), or DNA indexing, in the case of phage display libraries (Larman et al, 2011).…”