Quantitative and Qualitative Difference in Antibody Response against Omicron and Ancestral SARS-CoV-2 after Third and Fourth Vaccination

Waning immunity against SARS-CoV-2 and the emergence of variants, especially of the most distant variant, Omicron, affect titers of neutralizing antibodies in the sera of vaccinated individuals. Thus, two vaccinations with the mRNA vaccine BNT162b fail to induce neutralizing antibodies against the O...

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Main Authors: Sascha Hein, Ines Mhedhbi, Tobias Zahn, Catarina Sabino, Nuka Ivalu Benz, Younes Husria, Patricia Maria Renelt, Floriane Braun, Doris Oberle, Thorsten J. Maier, Christoph Hildt, Eberhard Hildt
Format: Article
Language:English
Published: MDPI AG 2022-05-01
Series:Vaccines
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Online Access:https://www.mdpi.com/2076-393X/10/5/796
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author Sascha Hein
Ines Mhedhbi
Tobias Zahn
Catarina Sabino
Nuka Ivalu Benz
Younes Husria
Patricia Maria Renelt
Floriane Braun
Doris Oberle
Thorsten J. Maier
Christoph Hildt
Eberhard Hildt
author_facet Sascha Hein
Ines Mhedhbi
Tobias Zahn
Catarina Sabino
Nuka Ivalu Benz
Younes Husria
Patricia Maria Renelt
Floriane Braun
Doris Oberle
Thorsten J. Maier
Christoph Hildt
Eberhard Hildt
author_sort Sascha Hein
collection DOAJ
description Waning immunity against SARS-CoV-2 and the emergence of variants, especially of the most distant variant, Omicron, affect titers of neutralizing antibodies in the sera of vaccinated individuals. Thus, two vaccinations with the mRNA vaccine BNT162b fail to induce neutralizing antibodies against the Omicron variant. A first booster vaccination increases Omicron-RBD-binding IgG and IgA and neutralizing capacity. In comparison, the Wuhan isolate titers of the Omicron variant binding antibodies are 8.5 lower. After a third vaccination, induction of Omicron-RBD- and Wuhan-RBD-binding antibodies follows the same kinetic. Five to six months after the third vaccination, there are still Omicron-RBD-binding antibodies detectable, but 35.9 percent of the analyzed sera fail to neutralize the Omicron variant, while all sera efficiently neutralize the Delta isolate. In the case of the Wuhan-RBD, a significantly larger number of stable antigen–antibody complexes is formed than in Omicron-RBD. A fourth vaccination with mRNA-1273 temporarily restores levels of Omicron-, Delta- and Wuhan-specific antibodies. Comparing different booster strategies revealed that the breadth of the immune response is not affected by the vaccination regimen. Taken together, these data indicate that booster vaccinations (third and fourth dose) increase the breadth of the immune response, but there is a qualitative difference of antibodies with respect to the stability of antigen–antibody complexes and persistence of antibody titers.
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spelling doaj.art-07d404f6cbec4e87a0ed89be587c78372023-11-23T13:27:24ZengMDPI AGVaccines2076-393X2022-05-0110579610.3390/vaccines10050796Quantitative and Qualitative Difference in Antibody Response against Omicron and Ancestral SARS-CoV-2 after Third and Fourth VaccinationSascha Hein0Ines Mhedhbi1Tobias Zahn2Catarina Sabino3Nuka Ivalu Benz4Younes Husria5Patricia Maria Renelt6Floriane Braun7Doris Oberle8Thorsten J. Maier9Christoph Hildt10Eberhard Hildt11Department of Virology, Paul-Ehrlich-Institut, Paul-Ehrlich Street 51-59, D-63225 Langen, GermanyDepartment of Virology, Paul-Ehrlich-Institut, Paul-Ehrlich Street 51-59, D-63225 Langen, GermanyDepartment of Virology, Paul-Ehrlich-Institut, Paul-Ehrlich Street 51-59, D-63225 Langen, GermanyDepartment of Virology, Paul-Ehrlich-Institut, Paul-Ehrlich Street 51-59, D-63225 Langen, GermanyDepartment of Virology, Paul-Ehrlich-Institut, Paul-Ehrlich Street 51-59, D-63225 Langen, GermanyDepartment of Virology, Paul-Ehrlich-Institut, Paul-Ehrlich Street 51-59, D-63225 Langen, GermanyDepartment of Virology, Paul-Ehrlich-Institut, Paul-Ehrlich Street 51-59, D-63225 Langen, GermanyDepartment of Virology, Paul-Ehrlich-Institut, Paul-Ehrlich Street 51-59, D-63225 Langen, GermanySafety of Medicinal Products and Medical Devices Division, Paul-Ehrlich-Institut, D-63325 Langen, GermanySafety of Medicinal Products and Medical Devices Division, Paul-Ehrlich-Institut, D-63325 Langen, GermanyMain-Kinzig-Kliniken, D-63571 Gelnhausen, GermanyDepartment of Virology, Paul-Ehrlich-Institut, Paul-Ehrlich Street 51-59, D-63225 Langen, GermanyWaning immunity against SARS-CoV-2 and the emergence of variants, especially of the most distant variant, Omicron, affect titers of neutralizing antibodies in the sera of vaccinated individuals. Thus, two vaccinations with the mRNA vaccine BNT162b fail to induce neutralizing antibodies against the Omicron variant. A first booster vaccination increases Omicron-RBD-binding IgG and IgA and neutralizing capacity. In comparison, the Wuhan isolate titers of the Omicron variant binding antibodies are 8.5 lower. After a third vaccination, induction of Omicron-RBD- and Wuhan-RBD-binding antibodies follows the same kinetic. Five to six months after the third vaccination, there are still Omicron-RBD-binding antibodies detectable, but 35.9 percent of the analyzed sera fail to neutralize the Omicron variant, while all sera efficiently neutralize the Delta isolate. In the case of the Wuhan-RBD, a significantly larger number of stable antigen–antibody complexes is formed than in Omicron-RBD. A fourth vaccination with mRNA-1273 temporarily restores levels of Omicron-, Delta- and Wuhan-specific antibodies. Comparing different booster strategies revealed that the breadth of the immune response is not affected by the vaccination regimen. Taken together, these data indicate that booster vaccinations (third and fourth dose) increase the breadth of the immune response, but there is a qualitative difference of antibodies with respect to the stability of antigen–antibody complexes and persistence of antibody titers.https://www.mdpi.com/2076-393X/10/5/796SARS-CoV-2OmicronBNT162b2second boosterantibody response
spellingShingle Sascha Hein
Ines Mhedhbi
Tobias Zahn
Catarina Sabino
Nuka Ivalu Benz
Younes Husria
Patricia Maria Renelt
Floriane Braun
Doris Oberle
Thorsten J. Maier
Christoph Hildt
Eberhard Hildt
Quantitative and Qualitative Difference in Antibody Response against Omicron and Ancestral SARS-CoV-2 after Third and Fourth Vaccination
Vaccines
SARS-CoV-2
Omicron
BNT162b2
second booster
antibody response
title Quantitative and Qualitative Difference in Antibody Response against Omicron and Ancestral SARS-CoV-2 after Third and Fourth Vaccination
title_full Quantitative and Qualitative Difference in Antibody Response against Omicron and Ancestral SARS-CoV-2 after Third and Fourth Vaccination
title_fullStr Quantitative and Qualitative Difference in Antibody Response against Omicron and Ancestral SARS-CoV-2 after Third and Fourth Vaccination
title_full_unstemmed Quantitative and Qualitative Difference in Antibody Response against Omicron and Ancestral SARS-CoV-2 after Third and Fourth Vaccination
title_short Quantitative and Qualitative Difference in Antibody Response against Omicron and Ancestral SARS-CoV-2 after Third and Fourth Vaccination
title_sort quantitative and qualitative difference in antibody response against omicron and ancestral sars cov 2 after third and fourth vaccination
topic SARS-CoV-2
Omicron
BNT162b2
second booster
antibody response
url https://www.mdpi.com/2076-393X/10/5/796
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