Landscape of infection enhancing antibodies in COVID-19 and healthy donors

Hendra S Ismanto; Zichang Xu; Dianita S Saputri; Jan Wilamowski; Songling Li; Dendi K Nugraha; Yasuhiko Horiguchi; Masato Okada; Hisashi Arase; Daron M Standley

doi:10.1016/j.csbj.2022.11.001

Landscape of infection enhancing antibodies in COVID-19 and healthy donors

Comput Struct Biotechnol J. 2022:20:6033-6040. doi: 10.1016/j.csbj.2022.11.001. Epub 2022 Nov 4.

Authors

Hendra S Ismanto¹, Zichang Xu¹, Dianita S Saputri¹, Jan Wilamowski¹, Songling Li^{1

2

3}, Dendi K Nugraha⁴, Yasuhiko Horiguchi^{4

3}, Masato Okada^{5

6

3}, Hisashi Arase^{7

8

3}, Daron M Standley^{1

2

3}

Affiliations

¹ Department of Genome Informatics, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita 565-0871, Japan.
² Department of System Immunology, Immunology Frontier Research Center, Osaka University, 3-1 Yamadaoka, Suita 565-0871, Japan.
³ Center for Infectious Disease Education and Research, Osaka University, Osaka 565-0871, Japan.
⁴ Deparment of Molecular Bacteriology, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita 565-0871, Japan.
⁵ Deparment of Oncogene Research, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita 565-0871, Japan.
⁶ Department of Oncogene Research, Immunology Frontier Research Center, Osaka University, 3-1 Yamadaoka, Suita 565-0871, Japan.
⁷ Department of Immunochemistry, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita 565-0871, Japan.
⁸ Department of Immunochemistry, Immunology Frontier Research Center, Osaka University, 3-1 Yamadaoka, Suita 565-0871, Japan.

Abstract

To assess the frequency of SARS-CoV-2 infection in the general population, we searched over 64 million heavy chain antibody sequences from healthy unvaccinated, healthy BNT162b2 vaccinated and COVID-19 patient repertoires for sequences similar to 11 previously reported enhancing antibodies. Although the distribution of sequence identities was similar in all three groups of repertoires, the COVID-19 and healthy vaccinated hits were significantly more clonally expanded than healthy unvaccinated hits. Furthermore, among the tested hits, 17 out of 94 from COVID-19 and 9 out of 59 from healthy vaccinated, compared with only 2 out of 96 from healthy unvaccinated, bound to the enhancing epitope. A total of 9 of the 28 epitope-binding antibodies enhanced ACE2 receptor binding to the spike protein. Together, this study revealed that infection enhancing-like antibodies are far more frequent in COVID-19 patients or healthy vaccinated donors than in healthy unvaccinated donors, but a reservoir of potential enhancing antibodies exists in healthy donors that could potentially mature to actual enhancing antibodies upon infection.

Keywords: Antibody repertoire; COVID-19; Infection enhancing antibodies; InterClone; SARS-CoV-2.