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AuthorVogt, Anne-Cathrine
AuthorAugusto, Gilles
AuthorMartina, Byron
AuthorChang, Xinyue
AuthorNasrallah, Gheyath
AuthorSpeiser, Daniel
AuthorVogel, Monique
AuthorBachmann, Martin
AuthorMohsen, Mona
Available date2022-05-23T05:36:59Z
Publication Date2022-05
Publication NameVaccines
Identifierhttp://dx.doi.org/10.3390/vaccines10050743
CitationVogt, A.-C.S.; Augusto, G.; Martina, B.; Chang, X.; Nasrallah, G.; Speiser, D.E.; Vogel, M.; Bachmann, M.F.; Mohsen, M.O. Increased Receptor Affinity and Reduced Recognition by Specific Antibodies Contribute to Immune Escape of SARS-CoV-2 Variant Omicron. Vaccines 2022, 10, 743. https://doi.org/10.3390/vaccines10050743
URIhttp://hdl.handle.net/10576/31475
AbstractIn this report, we mechanistically reveal how the Variant of Concern (VOC) SARS-CoV-2 Omicron (B.1.1.529) escapes neutralizing antibody responses, by physio-chemical characterization of this variant in comparison to the wild-type Wuhan and the Delta variant (B.1.617.2). Convalescent sera, as well as sera obtained from participants who received two or three doses of mRNA vaccines (Moderna-mRNA-1273® or Pfizer-BNT162b2®), were used for comparison in this study. Our data demonstrate that both Delta, as well as Omicron variants, exhibit a higher affinity for the receptor ACE2, facilitating infection and causing antibody escape by receptor affinity (affinity escape), due to the reduced ability of antibodies to compete with RBD-receptor interaction and virus neutralization. In contrast, only Omicron but not the Delta variant escaped antibody recognition, most likely because only Omicron exhibits the mutation at E484A, a position associated with reduced recognition, resulting in further reduced neutralization (specificity escape). Nevertheless, the immunizations with RNA-based vaccines resulted in marked viral neutralization in vitro for all strains, compatible with the fact that Omicron is still largely susceptible to vaccination-induced antibodies, despite affinity- and specificity escape.
SponsorThis research was funded by Saiba, A.G., the Swiss National Science Foundation (SNF grants 31003_185114 and IZRPZO_194968).
Languageen
PublisherMDPI
SubjectOmicron
Delta
SARS-CoV-2
antibody
TitleIncreased Receptor Affinity and Reduced Recognition by Specific Antibodies Contribute to Immune Escape of SARS-CoV-2 Variant Omicron
TypeArticle
Issue Number5
Volume Number10
ESSN2076-393X
dc.accessType Open Access


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