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SARS-COV-2 OMICRON-B. 1.1. 529 LEADS TO WIDESPREAD ESCAPE FROM NEUTRALIZING ANTIBODY RESPONSES
https://www.arca.fiocruz.br/handle/icict/50615
Author
Dejnirattisai, Wanwisa
Huo, Jiandong
Zhou, Daming
Zahradník, Jirí
Supasa, Piyada
Liu, Chang
Duyvesteyn, Helen M.E.
Ginn, Helen M.
Mentzer, Alexander J.
Tuekprakhon, Aekkachai
Nutalai, Rungtiwa
Wang, Beibei
Dijokaite, Aiste
Khan, Suman
Avinoam, Ori
Bahar, Mohammad
Skelly, Donal
Adele, Sandra
Johnson, Sile Ann
Amini, Ali
Ritter, Thomas G.
Mason, Chris
Dold, Christina
Pan, Daniel
Assadi, Sara
Bellass, Adam
Omo-Dare, Nicola
Koeckerling, David
Flaxman, Amy
Jenkin, Daniel
Aley, Parvinder K.
Voysey, Merryn
Clemens, Sue Ann Costa
Naveca, Felipe Gomes
Nascimento, Valdinete
Nascimento, Fernanda
Costa, Cristiano Fernandes da
Resende, Paola Cristina
Pauvolid-Correa, Alex
Siqueira, Marilda M.
Baillie, Vicky
Serafin, Natali
Kwatra, Gaurav
Silva, Kelly da
Madhi, Shabir A.
Nunes, Marta C.
Malik, Tariq
Openshaw, Peter J. M.
Baillie, J. Kenneth
Semple, Malcolm G.
Townsend, Alain R.
Huang, Kuan-Ying A.
Tan, Tiong Kit
Carroll, Miles W.
Klenerman, Paul
Barnes, Eleanor
Dunachie, Susanna J.
Constantinides, Bede
Webster, Hermione
Crook, Derrick
Pollard, Andrew J.
Lambe, Teresa
OPTIC Consortium
ISARIC4C Consortium
Paterson, Neil G.
Williams, Mark A.
Hall, David R.
Fry, Elizabeth E.
Mongkolsapaya, Juthathip
Ren, Jingshan
Schreiber, Gideon
Stuart, David I.
Screaton, Gavin R.
Huo, Jiandong
Zhou, Daming
Zahradník, Jirí
Supasa, Piyada
Liu, Chang
Duyvesteyn, Helen M.E.
Ginn, Helen M.
Mentzer, Alexander J.
Tuekprakhon, Aekkachai
Nutalai, Rungtiwa
Wang, Beibei
Dijokaite, Aiste
Khan, Suman
Avinoam, Ori
Bahar, Mohammad
Skelly, Donal
Adele, Sandra
Johnson, Sile Ann
Amini, Ali
Ritter, Thomas G.
Mason, Chris
Dold, Christina
Pan, Daniel
Assadi, Sara
Bellass, Adam
Omo-Dare, Nicola
Koeckerling, David
Flaxman, Amy
Jenkin, Daniel
Aley, Parvinder K.
Voysey, Merryn
Clemens, Sue Ann Costa
Naveca, Felipe Gomes
Nascimento, Valdinete
Nascimento, Fernanda
Costa, Cristiano Fernandes da
Resende, Paola Cristina
Pauvolid-Correa, Alex
Siqueira, Marilda M.
Baillie, Vicky
Serafin, Natali
Kwatra, Gaurav
Silva, Kelly da
Madhi, Shabir A.
Nunes, Marta C.
Malik, Tariq
Openshaw, Peter J. M.
Baillie, J. Kenneth
Semple, Malcolm G.
Townsend, Alain R.
Huang, Kuan-Ying A.
Tan, Tiong Kit
Carroll, Miles W.
Klenerman, Paul
Barnes, Eleanor
Dunachie, Susanna J.
Constantinides, Bede
Webster, Hermione
Crook, Derrick
Pollard, Andrew J.
Lambe, Teresa
OPTIC Consortium
ISARIC4C Consortium
Paterson, Neil G.
Williams, Mark A.
Hall, David R.
Fry, Elizabeth E.
Mongkolsapaya, Juthathip
Ren, Jingshan
Schreiber, Gideon
Stuart, David I.
Screaton, Gavin R.
Affilliation
Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, The Wellcome Centre for Human Genetics, Oxford, UK.
Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, The Wellcome Centre for Human Genetics, Oxford, UK / Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK.
Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot, Israel.
Diamond Light Source Ltd, Harwell Science & Innovation Campus, Didcot, UK.
Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
Translational Gastroenterology Unit, University of Oxford, Oxford, UK.
NIHR Oxford Biomedical Research Centre, Oxford, UK.
Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
Department of Infectious Diseases and HIV Medicine, University Hospitals of Leicester NHS Trust, Leicester, UK.
Department of Respiratory Sciences, University of Leicester, Leicester, UK.
Medical Sciences Division, University of Oxford, Oxford, UK.
Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Institute of Global Health, University of Siena, Siena, Brazil.
Fundação Oswaldo Cruz. Fiocruz Amazônia - Instituto Leônidas e Maria Deane. Laboratório de Ecologia de Doenças Transmissíveis na Amazônia. Manaus, Amazonas, Brasil.
Fundação de Vigilância em Saúde do Amazonas. Manaus, Amazonas, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de vírus respiratórios. Rio de Janeiro, RJ, Brasil.
Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, TX, USA.
South African Medical Research Council, Vaccines and Infectious Diseases Analytics Research Unit, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, The Wellcome Centre for Human Genetics, Oxford, UK.
Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, The Wellcome Centre for Human Genetics, Oxford, UK / Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK.
Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot, Israel.
Diamond Light Source Ltd, Harwell Science & Innovation Campus, Didcot, UK.
Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
Translational Gastroenterology Unit, University of Oxford, Oxford, UK.
NIHR Oxford Biomedical Research Centre, Oxford, UK.
Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
Department of Infectious Diseases and HIV Medicine, University Hospitals of Leicester NHS Trust, Leicester, UK.
Department of Respiratory Sciences, University of Leicester, Leicester, UK.
Medical Sciences Division, University of Oxford, Oxford, UK.
Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Institute of Global Health, University of Siena, Siena, Brazil.
Fundação Oswaldo Cruz. Fiocruz Amazônia - Instituto Leônidas e Maria Deane. Laboratório de Ecologia de Doenças Transmissíveis na Amazônia. Manaus, Amazonas, Brasil.
Fundação de Vigilância em Saúde do Amazonas. Manaus, Amazonas, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de vírus respiratórios. Rio de Janeiro, RJ, Brasil.
Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, TX, USA.
South African Medical Research Council, Vaccines and Infectious Diseases Analytics Research Unit, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
Abstract in Portuguese
A Variante de Preocupação Ômicron (B.1.1.529) trouxe uma grande expansão mundial dos contágios pelo SARS-CoV-2, mesmo em países onde a imunização contra o vírus já estava avançada. Para compreender como a coleção de mutações da Glicoproteína S da Ômicron leva ao escape da resposta imunológica, um esforço internacional de pesquisa que incluiu cientistas da Rede Genômica Fiocruz analisou as estruturas de proteínas, além da neutralização da capacidade de causar infecção ao expôr amostras da Ômicron a diferentes preparados contendo anticorpos como: 1) o soro de pacientes infectados com outras amostras do vírus, 2) os chamados “anticorpos monoclonais” selecionados em laboratório, e 3) o soro de pessoas vacinadas.O presente artigo, fruto desta colaboração para o estudo de múltiplos fatores envolvidos no escape da resposta imune apresentado pela Ômicron, demonstrou que a nova variante é quase 17 vezes mais resistente à neutralização pelos anticorpos gerados em resposta a uma linhagem da primeira onda da pandemia. O estudo mostra ainda que um esquema vacinal de três doses aumenta consideravelmente a resposta ao vírus, incluindo a neutralização da variante Ômicron, que não era suficiente apenas com duas doses do imunizante. O artigo mostra ainda que a estrutura de porções da Glicoproteína S da Ômicron estão envolvidas em “compensar” a ação de anticorpos através de uma ligação mais forte à ACE2, molécula que atua como receptor viral nas células humanas.
Abstract
On 24th November 2021, the sequence of a new SARS-CoV-2 viral isolate Omicron-B.1.1.529 was announced, containing far more mutations in Spike (S) than previously reported variants. Neutralization titers of Omicron by sera from vaccinees and convalescent subjects infected with early pandemic Alpha, Beta, Gamma, or Delta are substantially reduced, or the sera failed to neutralize. Titers against Omicron are boosted by third vaccine doses and are high in both vaccinated individuals and those infected by Delta. Mutations in Omicron knock out or substantially reduce neutralization by most of the large panel of potent monoclonal antibodies and antibodies under commercial development. Omicron S has structural changes from earlier viruses and uses mutations that confer tight binding to ACE2 to unleash evolution driven by immune escape. This leads to a large number of mutations in the ACE2 binding site and rebalances receptor affinity to that of earlier pandemic viruses.
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