Immunodominant antibody responses directed to SARS-CoV-2 hotspot mutation sites and risk of immune escape

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dc.contributor.authorOliveira, Jamille Ramos
dc.contributor.authorRuiz, Cesar Manuel Remuzgo
dc.contributor.authorMachado, Rafael Rahal Guaragna
dc.contributor.authorMagawa, Jhosiene Yukari
dc.contributor.authorDaher, Isabela Pazotti
dc.contributor.authorUrbanski, Alysson Henrique
dc.contributor.authorSchmitz, Gabriela Justamante Händel
dc.contributor.authorArcuri, Helen Andrade [UNESP]
dc.contributor.authorFerreira, Marcelo Alves
dc.contributor.authorSasahara, Greyce Luri
dc.contributor.authorde Medeiros, Giuliana Xavier
dc.contributor.authorJúnior, Roberto Carlos Vieira Silva
dc.contributor.authorDurigon, Edison Luiz
dc.contributor.authorBoscardin, Silvia Beatriz
dc.contributor.authorRosa, Daniela Santoro
dc.contributor.authorSchechtman, Deborah
dc.contributor.authorNakaya, Helder I.
dc.contributor.authorCunha-Neto, Edecio
dc.contributor.authorGadermaier, Gabriele
dc.contributor.authorKalil, Jorge
dc.contributor.authorCoelho, Verônica
dc.contributor.authorSantos, Keity Souza
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.contributor.institutionInstituto Nacional de Ciências e Tecnologia (iii-INCT)
dc.contributor.institutionUniversidade Estadual Paulista (UNESP)
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionHospital Israelita Albert Einstein
dc.contributor.institutionParis Lodron University Salzburg
dc.date.accessioned2023-07-29T13:38:11Z
dc.date.available2023-07-29T13:38:11Z
dc.date.issued2023-01-05
dc.description.abstractIntroduction: 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.en
dc.description.affiliationDepartamento de Clínica Médica Disciplina de Alergia e Imunologia Clínica Faculdade de Medicina da Universidade de São Paulo, SP
dc.description.affiliationLaboratório de Imunologia LIM19 Instituto do Coração (InCor) Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP) São Paulo da Universidade de São Paulo
dc.description.affiliationInstituto de Investigação em Imunologia Instituto Nacional de Ciências e Tecnologia – instituto de investigação em imunologia Instituto Nacional de Ciências e Tecnologia (iii-INCT)
dc.description.affiliationDepartamento de Microbiologia Instituto de Ciências Biomédicas Universidade de São Paulo, SP
dc.description.affiliationDepartamento de Análises Clínicas e Toxicológicas Faculdade de Ciências Farmacêuticas Universidade de São Paulo, SP
dc.description.affiliationCentro de Estudos de Insetos Sociais Departamento de Biologia Instituto de Biociências de Rio Claro Universidade Estadual Paulista, SP
dc.description.affiliationLaboratório de Biologia Celular Laboratório de Investigação Médica 59 (LIM59) Departamento de Patologia Faculdade de Medicina Faculdade de Medicina da Universidade de São Paulo (FMUSP) Universidade de São Paulo
dc.description.affiliationPlataforma Científica Pasteur-USP, SP
dc.description.affiliationDepartamento de Parasitologia Instituto de Ciências Biomédicas Universidade de São Paulo, SP
dc.description.affiliationDepartamento de Microbiologia Imunologia e Parasitologia Universidade Federal de São Paulo (UNIFESP/EPM, SP
dc.description.affiliationDepartamento de Bioquímica instituto de Química Universidade de São Paulo, SP
dc.description.affiliationHospital Israelita Albert Einstein, SP
dc.description.affiliationDepartment of Biosciences and Medical Biology Paris Lodron University Salzburg
dc.description.affiliationUnespCentro de Estudos de Insetos Sociais Departamento de Biologia Instituto de Biociências de Rio Claro Universidade Estadual Paulista, SP
dc.identifierhttp://dx.doi.org/10.3389/fimmu.2022.1010105
dc.identifier.citationFrontiers in Immunology, v. 13.
dc.identifier.doi10.3389/fimmu.2022.1010105
dc.identifier.issn1664-3224
dc.identifier.scopus2-s2.0-85146594091
dc.identifier.urihttp://hdl.handle.net/11449/248232
dc.language.isoeng
dc.relation.ispartofFrontiers in Immunology
dc.sourceScopus
dc.subjectbetacoronavirus
dc.subjectimmune pressure
dc.subjectlinear antibody epitopes
dc.subjectpeptide array
dc.subjectRBD
dc.subjectsarbecovirus
dc.titleImmunodominant antibody responses directed to SARS-CoV-2 hotspot mutation sites and risk of immune escapeen
dc.typeArtigo

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