Antibody Avidity and Neutralizing Response against SARS-CoV-2 Omicron Variant after Infection or Vaccination

Background. The recently emerged SARS-CoV-2 Omicron variant exhibits several mutations on the spike protein, enabling it to escape the immunity elicited by natural infection or vaccines. Avidity is the strength of binding between an antibody and its specific epitope. The SARS-CoV-2 spike protein bin...

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Main Authors: Francesca Dapporto, Serena Marchi, Margherita Leonardi, Pietro Piu, Piero Lovreglio, Nicola Decaro, Nicola Buonvino, Angela Stufano, Eleonora Lorusso, Emilio Bombardieri, Antonella Ruello, Simonetta Viviani, Eleonora Molesti, Claudia Maria Trombetta, Alessandro Manenti, Emanuele Montomoli
Format: Article
Language:English
Published: Wiley 2022-01-01
Series:Journal of Immunology Research
Online Access:http://dx.doi.org/10.1155/2022/4813199
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author Francesca Dapporto
Serena Marchi
Margherita Leonardi
Pietro Piu
Piero Lovreglio
Nicola Decaro
Nicola Buonvino
Angela Stufano
Eleonora Lorusso
Emilio Bombardieri
Antonella Ruello
Simonetta Viviani
Eleonora Molesti
Claudia Maria Trombetta
Alessandro Manenti
Emanuele Montomoli
author_facet Francesca Dapporto
Serena Marchi
Margherita Leonardi
Pietro Piu
Piero Lovreglio
Nicola Decaro
Nicola Buonvino
Angela Stufano
Eleonora Lorusso
Emilio Bombardieri
Antonella Ruello
Simonetta Viviani
Eleonora Molesti
Claudia Maria Trombetta
Alessandro Manenti
Emanuele Montomoli
author_sort Francesca Dapporto
collection DOAJ
description Background. The recently emerged SARS-CoV-2 Omicron variant exhibits several mutations on the spike protein, enabling it to escape the immunity elicited by natural infection or vaccines. Avidity is the strength of binding between an antibody and its specific epitope. The SARS-CoV-2 spike protein binds to its cellular receptor with high affinity and is the primary target of neutralizing antibodies. Therefore, protective antibodies should show high avidity. This study aimed at investigating the avidity of receptor-binding domain (RBD) binding antibodies and their neutralizing activity against the Omicron variant in SARS-CoV-2 infected patients and vaccinees. Methods. Samples were collected from 42 SARS-CoV-2 infected patients during the first pandemic wave, 50 subjects who received 2 doses of mRNA vaccine before the Omicron wave, 44 subjects who received 3 doses of mRNA vaccine, and 35 subjects who received heterologous vaccination (2 doses of adenovirus-based vaccine plus mRNA vaccine) during the Omicron wave. Samples were tested for the avidity of RBD-binding IgG and neutralizing antibodies against the wild-type SARS-CoV-2 virus and the Omicron variant. Results. In patients, RBD-binding IgG titers against the wild-type virus increased with time, but remained low. High neutralizing titers against the wild-type virus were not matched by high avidity or neutralizing activity against the Omicron variant. Vaccinees showed higher avidity than patients. Two vaccine doses elicited the production of neutralizing antibodies, but low avidity for the wild-type virus; antibody levels against the Omicron variant were even lower. Conversely, 3 doses of vaccine elicited high avidity and high neutralizing antibodies against both the wild-type virus and the Omicron variant. Conclusions. Repeated vaccination increases antibody avidity against the spike protein of the Omicron variant, suggesting that antibodies with high avidity and high neutralizing potential increase cross-protection against variants that carry several mutations on the RBD.
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spelling doaj-art-15a1190966644b8fba5a10484e4ecf452025-02-03T01:22:53ZengWileyJournal of Immunology Research2314-71562022-01-01202210.1155/2022/4813199Antibody Avidity and Neutralizing Response against SARS-CoV-2 Omicron Variant after Infection or VaccinationFrancesca Dapporto0Serena Marchi1Margherita Leonardi2Pietro Piu3Piero Lovreglio4Nicola Decaro5Nicola Buonvino6Angela Stufano7Eleonora Lorusso8Emilio Bombardieri9Antonella Ruello10Simonetta Viviani11Eleonora Molesti12Claudia Maria Trombetta13Alessandro Manenti14Emanuele Montomoli15VisMederi srlDepartmente of Molecular and Developmental MedicineVismederi Research SrlVisMederi srlInterdisciplinary Department of MedicineDepartment of Veterinary MedicineU.O.C. Penitentiary Medicine-Department of Territorial CareInterdisciplinary Department of MedicineDepartment of Veterinary MedicineHumanitas GavazzeniHumanitas GavazzeniDepartmente of Molecular and Developmental MedicineVismederi Research SrlDepartmente of Molecular and Developmental MedicineVisMederi srlVisMederi srlBackground. The recently emerged SARS-CoV-2 Omicron variant exhibits several mutations on the spike protein, enabling it to escape the immunity elicited by natural infection or vaccines. Avidity is the strength of binding between an antibody and its specific epitope. The SARS-CoV-2 spike protein binds to its cellular receptor with high affinity and is the primary target of neutralizing antibodies. Therefore, protective antibodies should show high avidity. This study aimed at investigating the avidity of receptor-binding domain (RBD) binding antibodies and their neutralizing activity against the Omicron variant in SARS-CoV-2 infected patients and vaccinees. Methods. Samples were collected from 42 SARS-CoV-2 infected patients during the first pandemic wave, 50 subjects who received 2 doses of mRNA vaccine before the Omicron wave, 44 subjects who received 3 doses of mRNA vaccine, and 35 subjects who received heterologous vaccination (2 doses of adenovirus-based vaccine plus mRNA vaccine) during the Omicron wave. Samples were tested for the avidity of RBD-binding IgG and neutralizing antibodies against the wild-type SARS-CoV-2 virus and the Omicron variant. Results. In patients, RBD-binding IgG titers against the wild-type virus increased with time, but remained low. High neutralizing titers against the wild-type virus were not matched by high avidity or neutralizing activity against the Omicron variant. Vaccinees showed higher avidity than patients. Two vaccine doses elicited the production of neutralizing antibodies, but low avidity for the wild-type virus; antibody levels against the Omicron variant were even lower. Conversely, 3 doses of vaccine elicited high avidity and high neutralizing antibodies against both the wild-type virus and the Omicron variant. Conclusions. Repeated vaccination increases antibody avidity against the spike protein of the Omicron variant, suggesting that antibodies with high avidity and high neutralizing potential increase cross-protection against variants that carry several mutations on the RBD.http://dx.doi.org/10.1155/2022/4813199
spellingShingle Francesca Dapporto
Serena Marchi
Margherita Leonardi
Pietro Piu
Piero Lovreglio
Nicola Decaro
Nicola Buonvino
Angela Stufano
Eleonora Lorusso
Emilio Bombardieri
Antonella Ruello
Simonetta Viviani
Eleonora Molesti
Claudia Maria Trombetta
Alessandro Manenti
Emanuele Montomoli
Antibody Avidity and Neutralizing Response against SARS-CoV-2 Omicron Variant after Infection or Vaccination
Journal of Immunology Research
title Antibody Avidity and Neutralizing Response against SARS-CoV-2 Omicron Variant after Infection or Vaccination
title_full Antibody Avidity and Neutralizing Response against SARS-CoV-2 Omicron Variant after Infection or Vaccination
title_fullStr Antibody Avidity and Neutralizing Response against SARS-CoV-2 Omicron Variant after Infection or Vaccination
title_full_unstemmed Antibody Avidity and Neutralizing Response against SARS-CoV-2 Omicron Variant after Infection or Vaccination
title_short Antibody Avidity and Neutralizing Response against SARS-CoV-2 Omicron Variant after Infection or Vaccination
title_sort antibody avidity and neutralizing response against sars cov 2 omicron variant after infection or vaccination
url http://dx.doi.org/10.1155/2022/4813199
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