As researchers work around the clock to find ways to stop SARS-CoV-2, one feature—the ‘crown’ of spike proteins after which the family of viruses is named—has received a lot of attention. SARS-CoV-2, like its deadly cousins SARS-CoV and MERS-CoV, uses its spike protein to attach to and invade cells. Understanding how the human immune system recognizes the spike protein is thus essential for designing more accurate diagnostics and vaccines against COVID-19.
When a person is infected with SARS-CoV-2, the antibodies they produce detect either small fragments of the virus in its 3D form (conformational epitopes) or a sequence of amino acids with no secondary structure (linear epitopes). However, one possible reason that early diagnostic tests targeting conformational epitopes were not as accurate as hoped is that other viruses may have similar 3D motifs. Furthermore, SARS-CoV-2 conformational epitopes might also be recognized by non-specific antibodies, potentially giving rise to false-positive results.
“Linear epitopes are a lot less likely to be recognized by non-specific antibodies due to their short sequences,” said Lisa F. P. Ng, a Senor Principal Investigator at A*STAR’s Singapore Immunology Network (SIgN). In a study published in Nature Communications, Ng and her team identified two linear epitopes of SARS-CoV-2 that were strongly and specifically recognized by antibodies from COVID-19 patients.
The researchers, led by study co-first authors Chek Meng Poh and Guillaume Carissimo, Research Fellows in Ng’s lab, exposed pools of five overlapping peptides covering the length of the SARS-CoV-2 spike protein to antibodies from patients who had developed COVID-19, healthy controls and those who had recovered from SARS, which struck in 2003.
Through multiple rounds of screening, the researchers found two peptides, S14P5 and S21P2, that were recognized by antibodies from COVID-19 patients but not SARS patients or healthy controls. Ng expects that these peptides will be useful for designing highly specific serological assays to determine the extent of exposure to SARS-CoV-2 in the population, as well as for measuring immune responses in clinical trials for vaccine candidates.
The researchers also showed that antibodies targeting S14P5 and S21P2 can neutralize or block SARS-CoV-2 infection. “Further studies will be needed to determine if these epitopes can be used as vaccine candidates to generate sufficient levels of antibodies in humans and protect against COVID-19,” said Ng. “Developing specific monoclonal antibodies against these epitopes as a potential treatment for COVID-19 would be the next step.”
The A*STAR-affiliated researchers contributing to this research are from the Singapore Immunology Network (SIgN).