|
Basic Characteristics of Mutations
|
|
Mutation Site
|
E484K |
|
Mutation Site Sentence
|
Considering that P44 bears the K417 mutation hotspot, we investigated the potential relevance of K417 mutations for antibody binding, by performing in silico equilibrium molecular dynamics simulations of beta (mutations: E484K, K417N, and N501Y) and gamma (mutations: E484K, K417T and N501Y) RBD variants interacting with the therapeutic mAb REGN10933, previously shown to present loss of neutralizing activity in a mutated K417N pseudovirus assay. |
|
Mutation Level
|
Amino acid level |
|
Mutation Type
|
Nonsynonymous substitution |
|
Gene/Protein/Region
|
RBD |
|
Standardized Encoding Gene
|
S
|
|
Genotype/Subtype
|
Beta;Gamma |
|
Viral Reference
|
-
|
|
Functional Impact and Mechanisms
|
|
Disease
|
COVID-19
|
|
Immune
|
Y |
|
Target Gene
|
-
|
|
Clinical and Epidemiological Correlations
|
|
Clinical Information
|
- |
|
Treatment
|
- |
|
Location
|
Brazil |
|
Literature Information
|
|
PMID
|
36685521
|
|
Title
|
Immunodominant antibody responses directed to SARS-CoV-2 hotspot mutation sites and risk of immune escape
|
|
Author
|
Oliveira JR,Ruiz CMR,Machado RRG,Magawa JY,Daher IP,Urbanski AH,Schmitz GJH,Arcuri HA,Ferreira MA,Sasahara GL,de Medeiros GX,Junior RCVS,Durigon EL,Boscardin SB,Rosa DS,Schechtman D,Nakaya HI,Cunha-Neto E,Gadermaier G,Kalil J,Coelho V,Santos KS
|
|
Journal
|
Frontiers in immunology
|
|
Journal Info
|
2023 Jan 5;13:1010105
|
|
Abstract
|
INTRODUCTION: Considering the likely need for the development of novel effective vaccines adapted to emerging relevant CoV-2 variants, the increasing knowledge of epitope recognition profile among convalescents and afterwards vaccinated with identification of immunodominant regions may provide important information. METHODS: We used an RBD peptide microarray to identify IgG and IgA binding regions in serum of 71 COVID-19 convalescents and 18 vaccinated individuals. RESULTS: We found a set of immunodominant RBD antibody epitopes, each recognized by more than 30% of the tested cohort, that differ among the two different groups and are within conserved regions among betacoronavirus. Of those, only one peptide, P44 (S415-429), recognized by 68% of convalescents, presented IgG and IgA antibody reactivity that positively correlated with nAb titers, suggesting that this is a relevant RBD region and a potential target of IgG/IgA neutralizing activity. DISCUSSION: This peptide is localized within the area of contact with ACE-2 and harbors the mutation hotspot site K417 present in gamma (K417T), beta (K417N), and omicron (K417N) variants of concern. The epitope profile of vaccinated individuals differed from convalescents, with a more diverse repertoire of immunodominant peptides, recognized by more than 30% of the cohort. Noteworthy, immunodominant regions of recognition by vaccinated coincide with mutation sites at Omicron BA.1, an important variant emerging after massive vaccination. Together, our data show that immune pressure induced by dominant antibody responses may favor hotspot mutation sites and the selection of variants capable of evading humoral response.
|
|
Sequence Data
|
-
|
|
|