Poster Presentation 8th Australasian Vaccines & Immunotherapeutics Development Meeting 2020

Two linear B cell epitopes on SARS-CoV-2 spike protein elicit neutralizing antibodies in COVID-19 patients (#108)

Chek Meng Poh 1 2 , Guillaume Carissimo 1 2 , Bei Wang 1 2 , Siti Naqiah Amrun 1 2 , Cheryl Lee 1 2 , Rhonda Chee 1 2 , Siew-Wai Fong 1 2 3 , Nicholas Yeo 1 2 , Sandy Wen-Hsin Lee 1 2 , Anthony Torres 1 2 4 , Yee-Sin Leo 5 6 7 8 , Mark Chen 6 9 , Seow-Yen Tan 10 , Louis Chai 5 11 , Shirin Kalimuddin 12 13 , Shirley Gek Kheng Seah 14 , Siew-Yee Thien 12 , Barnaby E Young 5 6 7 , David C Lye 5 6 7 8 , Brendon J Hanson 14 , Cheng-I Wang 1 2 , Laurent Renia 1 2 , Lisa Ng 1 2
  1. Infectious Diseases Horizontal Technology Centre, Agency of Science, Technology and Research, Singapore, SINGAPORE
  2. Singapore Immunology Network, Agency of Science, Technology and Research, Singapore
  3. Department of Biological Science, National University of Singapore, Singapore, SIngapore
  4. Department of Biochemistry, National University of Singapore, Singapore
  5. Department of Infectious Diseases, Tan Tock Seng Hospital, Singapore
  6. National Centre for Infectious Diseases, Singapore
  7. Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore
  8. Yong Loo Lin School of Medicine, National University of Singapore, Singapore
  9. Saw Swee Hock School of Public Health, National University of Singapore, Singapore
  10. Department of Infectious Diseases, Changi General Hospital, Singapore
  11. Department of Medicine, National University Hospital, Singapore
  12. Department of Infectious Diseases, Singapore General Hospital, Singapore
  13. Emerging Infectious Disease Program, Duke-NUS Medical School, Singapore
  14. Biological Defence Program, Defence Science Organizarion, Singapore

COVID-19, caused by SARS-CoV-2 coronavirus, has become a grave threat to global public health in 2020, causing over a million deaths and prompting governments worldwide to enter lockdowns to control the pandemic. The SARS-CoV-2 spike protein acts as the ligand to bind with human ACE2 to mediate viral entry into host cells. Thus, specific antibodies that interfere with this process are useful in halting the infection. To identify SARS-CoV-2 specific epitopes, we collected the sera of 25 convalescent patients during the first wave of COVID-19 infection in Singapore and 13 donors who recovered from SARS-CoV (SARS) infection in 2003 for analysis. Sera from COVID-19 patients, but not recalled SARS patients, contain antibodies that neutralize pseudotyped lentivirus expressing the SARS-CoV-2 spike protein. Furthermore, we screened these sera against the peptide libraries spanning the spike protein of SARS-CoV-2 and uncovered two specific linear B cell epitopes, S14P5 and S21P2, that were recognized only by COVID-19 patient sera. S14P5 is situated close to the receptor-binding domain (RBD) while S21P2 overlaps with the fusion peptide sequence, suggesting that specific antibodies against these regions may be able to interfere with viral entry into host cells. Indeed, depleting antibodies that recognize S14P5 and S21P2 decreased neutralization capacity of sera against pseudotyped lentivirus expressing the SARS-CoV-2 spike protein. In conclusion, antibodies against S14P5 and S21P2 can interfere with viral entry into host cells and prevent infection, indicating that they have considerable therapeutic potential to be used in COVID-19 treatments.