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

概要

SARS-CoV-2 infection can elicit not only neutralizing antibodies, but also infection enhancing antibodies, in humans. To date, a total of 11 monoclonal antibodies that target a common epitope in the N-terminal domain of the spike protein and facilitate binding of the receptor-binding domain (RBD) to human angiotensin-converting enzyme 2 (ACE2), have been reported. To assess the frequencies of these enhancing antibodies in the general population, I utilized a bioinformatics pipeline developed in the Genome Informatics laboratory to search over 64 million unique heavy chain sequences (55.4 million from healthy and 8.5 million from COVID-19 donor repertoires). The distributions of complementarity-determining region (CDR) sequence identities of search hits were very similar in healthy unvaccinated, healthy vaccinated and COVID-19 donors. However, the degree of clonal expansion was significantly higher in the COVID-19 and healthy vaccinated donors compared to healthy unvaccinated donors. Moreover, among the hits, 17 out of 94 tested COVID-19 antibodies, compared with 2 out of 96 healthy unvaccinated antibodies, bound to the enhancing epitope and promoted ACE2 binding. Based on these results, I estimated that the frequency of infection-enhancing antibodies within COVID-19 and healthy unvaccinated donors to be 100 and 3 per million clones, respectively. Taken together, I conclude that enhancing antibodies are far more frequent in COVID-19 patients than in healthy unvaccinated donors, but a large reservoir of highly similar antibodies exists in healthy donor repertoires that can mature into infection-enhancing antibodies upon infection.