Antibodies that recognize linear epitopes could form the basis of more accurate COVID-19 tests. 3D print of a spike protein on the surface of SARS-CoV-2, the virus that causes COVID-19.

© US National Institutes of Health

Getting the SARS-CoV-2 antibody response straight

29 Jun 2020

Two linear peptides identified by A*STAR researchers on the SARS-CoV-2 spike protein may improve the specificity of serological assays and show potential as vaccine candidates.

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).

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Poh, C. M., Carissimo, G., Wang, B., Amrun, S. N., Lee, C. Y. et al. Two linear epitopes on the SARS-CoV-2 spike protein that elicit neutralising antibodies in COVID-19 patients. Nature Communications 11, 2806 (2020) | article

About the Researcher

Lisa F.P. Ng

Senior Principal Investigator

Singapore Immunology Network
Lisa F.P. Ng obtained her PhD in molecular virology in coronaviruses from the National University of Singapore (NUS) in 2002. After joining A*STAR’s Genome Institute of Singapore (GIS) in 2002 as a postdoctoral fellow, she worked on viral diseases such as hepatitis, severe acute respiratory syndrome and influenza. Ng is currently the Executive Director of the A*STAR Graduate Academy (A*GA) and she holds a concurrent appointment as Senior Principal Investigator at the A*STAR Singapore Immunology Network (SIgN) where she focuses on the immune responses to arthritic arboviruses that are epidemic or highly endemic in the tropical region. Ng has won numerous accolades for her research, including the ASEAN ‘International Young Scientist and Technologist Award’ in 2008 and A*STAR’s ‘Most Inspiring Mentor Award’ in March 2013. She holds Adjunct Professorships at the Yong Loo Lin School of Medicine and the Duke-National University of Singapore Graduate Medical School.

This article was made for A*STAR Research by Wildtype Media Group