Academic Journal
Characterisation of the antibody-mediated selective pressure driving intra-host evolution of SARS-CoV-2 in prolonged infection.
| Title: | Characterisation of the antibody-mediated selective pressure driving intra-host evolution of SARS-CoV-2 in prolonged infection. |
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| Authors: | Michael Schoefbaenker, Theresa Günther, Eva Ulla Lorentzen, Marie-Luise Romberg, Marc Tim Hennies, Rieke Neddermeyer, Marlin Maybrit Müller, Alexander Mellmann, Chiara Robin Bojarzyn, Georg Lenz, Matthias Stelljes, Eike Roman Hrincius, Richard Vollenberg, Stephan Ludwig, Phil-Robin Tepasse, Joachim Ewald Kühn |
| Source: | PLoS Pathogens, Vol 20, Iss 10, p e1012624 (2024) |
| Publisher Information: | Public Library of Science (PLoS), 2024. |
| Publication Year: | 2024 |
| Collection: | LCC:Immunologic diseases. Allergy LCC:Biology (General) |
| Subject Terms: | Immunologic diseases. Allergy, RC581-607, Biology (General), QH301-705.5 |
| More Details: | Neutralising antibodies against the SARS-CoV-2 spike (S) protein are major determinants of protective immunity, though insufficient antibody responses may cause the emergence of escape mutants. We studied the humoral immune response causing intra-host evolution in a B-cell depleted, haemato-oncologic patient experiencing clinically severe, prolonged SARS-CoV-2 infection with a virus of lineage B.1.177.81. Following bamlanivimab treatment at an early stage of infection, the patient developed a bamlanivimab-resistant mutation, S:S494P. After five weeks of apparent genetic stability, the emergence of additional substitutions and deletions within the N-terminal domain (NTD) and the receptor binding domain (RBD) of S was observed. Notably, the composition and frequency of escape mutations changed in a short period with an unprecedented dynamic. The triple mutant S:Delta141-4 E484K S494P became dominant until virus elimination. Routine serology revealed no evidence of an antibody response in the patient. A detailed analysis of the variant-specific immune response by pseudotyped virus neutralisation test, surrogate virus neutralisation test, and immunoglobulin-capture enzyme immunoassay showed that the onset of an IgM-dominated antibody response coincided with the appearance of escape mutations. The formation of neutralising antibodies against S:Delta141-4 E484K S494P correlated with virus elimination. One year later, the patient experienced clinically mild re-infection with Omicron BA.1.18, which was treated with sotrovimab and resulted in an increase in Omicron-reactive antibodies. In conclusion, the onset of an IgM-dominated endogenous immune response in an immunocompromised patient coincided with the appearance of additional mutations in the NTD and RBD of S in a bamlanivimab-resistant virus. Although virus elimination was ultimately achieved, this humoral immune response escaped detection by routine diagnosis and created a situation temporarily favouring the rapid emergence of various antibody escape mutants with known epidemiological relevance. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 1553-7366 1553-7374 |
| Relation: | https://doaj.org/toc/1553-7366; https://doaj.org/toc/1553-7374 |
| DOI: | 10.1371/journal.ppat.1012624 |
| Access URL: | https://doaj.org/article/ebe092f1c6914f7e860e517dc2c22ecb |
| Accession Number: | edsdoj.be092f1c6914f7e860e517dc2c22ecb |
| Database: | Directory of Open Access Journals |
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| ISSN: | 15537366 15537374 |
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| DOI: | 10.1371/journal.ppat.1012624 |
| Published in: | PLoS Pathogens |
| Language: | English |