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Artikel ; Online: B cell somatic hypermutation following COVID-19 vaccination with Ad26.COV2.S.

Jacob-Dolan, Catherine / Lifton, Michelle / Powers, Olivia C / Miller, Jessica / Hachmann, Nicole P / Vu, Mya / Surve, Nehalee / Mazurek, Camille R / Fisher, Jana L / Rodrigues, Stefanie / Patio, Robert C / Anand, Trisha / Le Gars, Mathieu / Sadoff, Jerald / Schmidt, Aaron G / Barouch, Dan H

iScience

2024 Band 27, Heft 5, Seite(n) 109716

Abstract: The viral vector-based COVID-19 vaccine Ad26.COV2.S has been recommended by the WHO since 2021 and has been administered to over 200 million people. Prior studies have shown that Ad26.COV2.S induces durable neutralizing antibodies (NAbs) that increase in ...

Abstract	The viral vector-based COVID-19 vaccine Ad26.COV2.S has been recommended by the WHO since 2021 and has been administered to over 200 million people. Prior studies have shown that Ad26.COV2.S induces durable neutralizing antibodies (NAbs) that increase in coverage of variants over time, even in the absence of boosting or infection. Here, we studied humoral responses following Ad26.COV2.S vaccination in individuals enrolled in the initial Phase 1/2a trial of Ad26.COV2.S in 2020. Through 8 months post vaccination, serum NAb responses increased to variants, including B.1.351 (Beta) and B.1.617.2 (Delta), without additional boosting or infection. The level of somatic hypermutation, measured by nucleotide changes in the VDJ region of the heavy and light antibody chains, increased in Spike-specific B cells. Highly mutated mAbs from these sequences neutralized more SARS-CoV-2 variants than less mutated comparators. These findings suggest that the increase in NAb breadth over time following Ad26.COV2.S vaccination is mediated by affinity maturation.
Sprache	Englisch
Erscheinungsdatum	2024-04-09
Erscheinungsland	United States
Dokumenttyp	Journal Article
ISSN	2589-0042
ISSN (online)	2589-0042
DOI	10.1016/j.isci.2024.109716
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel: SARS-CoV-2 RBD dimers elicit response comparable to VLPs in mice.

Love, J / Rodriguez-Aponte, Sergio / Tostanoski, Lisa / Dalvie, Neil / Johnston, Ryan / Jacob-Dolan, Catherine / Powers, Olivia / Hachmann, Nicole / Miller, Jessica / Hall, Kevin / Siamatu, Mazuba / Mazurek, Camille / Surve, Nehalee / Barouch, Dan

Research square

2023

Abstract: We report the direct comparison of monomeric, dimeric and trimeric RBD protein subunit vaccines to a virus-like particle (VLP) displaying RBD. After two and three doses, a RBD dimer and trimer elicited antibody levels in mice comparable to an RBD-VLP. ... ...

Abstract	We report the direct comparison of monomeric, dimeric and trimeric RBD protein subunit vaccines to a virus-like particle (VLP) displaying RBD. After two and three doses, a RBD dimer and trimer elicited antibody levels in mice comparable to an RBD-VLP. Furthermore, an Omicron (BA.1) RBD hetero-dimer induced neutralizing activity similar to the RBD-VLP. A RBD hetero-dimer and RBD-VLP also shows comparable breadth to other SARS-CoV-2 variants-of-concern (VOCs).
Sprache	Englisch
Erscheinungsdatum	2023-04-28
Erscheinungsland	United States
Dokumenttyp	Preprint
DOI	10.21203/rs.3.rs-2692315/v1
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Substantial Neutralization Escape by SARS-CoV-2 Omicron Variants BQ.1.1 and XBB.1.

Miller, Jessica / Hachmann, Nicole P / Collier, Ai-Ris Y / Lasrado, Ninaad / Mazurek, Camille R / Patio, Robert C / Powers, Olivia / Surve, Nehalee / Theiler, James / Korber, Bette / Barouch, Dan H

The New England journal of medicine

2023 Band 388, Heft 7, Seite(n) 662–664

Mesh-Begriff(e)	Humans ; Antibodies, Neutralizing/genetics ; Antibodies, Neutralizing/immunology ; Antibodies, Viral/genetics ; Antibodies, Viral/immunology ; COVID-19/genetics ; COVID-19/immunology ; COVID-19/virology ; Immune Evasion/genetics ; Immune Evasion/immunology ; SARS-CoV-2/genetics ; SARS-CoV-2/immunology
Chemische Substanzen	Antibodies, Neutralizing ; Antibodies, Viral
Sprache	Englisch
Erscheinungsdatum	2023-01-18
Erscheinungsland	United States
Dokumenttyp	Letter ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	207154-x
ISSN	1533-4406 ; 0028-4793
ISSN (online)	1533-4406
ISSN	0028-4793
DOI	10.1056/NEJMc2214314
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Waning immunity and IgG4 responses following bivalent mRNA boosting.

Science advances

2024 Band 10, Heft 8, Seite(n) eadj9945

Abstract: Messenger RNA (mRNA) vaccines were highly effective against the ancestral SARS-CoV-2 strain, but the efficacy of bivalent mRNA boosters against XBB variants was substantially lower. Here, we show limited durability of neutralizing antibody (NAb) ... ...

Abstract	Messenger RNA (mRNA) vaccines were highly effective against the ancestral SARS-CoV-2 strain, but the efficacy of bivalent mRNA boosters against XBB variants was substantially lower. Here, we show limited durability of neutralizing antibody (NAb) responses against XBB variants and isotype switching to immunoglobulin G4 (IgG4) responses following bivalent mRNA boosting. Bivalent mRNA boosting elicited modest XBB.1-, XBB.1.5-, and XBB.1.16-specific NAbs that waned rapidly within 3 months. In contrast, bivalent mRNA boosting induced more robust and sustained NAbs against the ancestral WA1/2020 strain, suggesting immune imprinting. Following bivalent mRNA boosting, serum antibody responses were primarily IgG2 and IgG4 responses with poor Fc functional activity. In contrast, a third monovalent mRNA immunization boosted all isotypes including IgG1 and IgG3 with robust Fc functional activity. These data show substantial immune imprinting for the ancestral spike and isotype switching to IgG4 responses following bivalent mRNA boosting, with important implications for future booster designs and boosting strategies.
Mesh-Begriff(e)	Antibody Formation ; Immunoglobulin G ; Antibodies, Neutralizing ; Immunization ; RNA, Messenger/genetics ; mRNA Vaccines
Chemische Substanzen	Immunoglobulin G ; Antibodies, Neutralizing ; RNA, Messenger ; mRNA Vaccines
Sprache	Englisch
Erscheinungsdatum	2024-02-23
Erscheinungsland	United States
Dokumenttyp	Journal Article
ZDB-ID	2810933-8
ISSN	2375-2548 ; 2375-2548
ISSN (online)	2375-2548
ISSN	2375-2548
DOI	10.1126/sciadv.adj9945
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Neutralization escape by SARS-CoV-2 Omicron subvariant BA.2.86.

Lasrado, Ninaad / Collier, Ai-Ris Y / Hachmann, Nicole P / Miller, Jessica / Rowe, Marjorie / Schonberg, Eleanor D / Rodrigues, Stefanie L / LaPiana, Austin / Patio, Robert C / Anand, Trisha / Fisher, Jana / Mazurek, Camille R / Guan, Ruoran / Wagh, Kshitij / Theiler, James / Korber, Bette T / Barouch, Dan H

Vaccine

2023 Band 41, Heft 47, Seite(n) 6904–6909

Abstract: The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variant BA.2.86 has over 30 mutations in spike compared with BA.2 and XBB.1.5, which raised the possibility that BA.2.86 might evade neutralizing antibodies (NAbs) induced by vaccination or ...

Abstract	The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variant BA.2.86 has over 30 mutations in spike compared with BA.2 and XBB.1.5, which raised the possibility that BA.2.86 might evade neutralizing antibodies (NAbs) induced by vaccination or infection. In this study, we show that NAb titers are substantially lower to BA.2.86 compared with BA.2 but are similar or slightly higher than to other current circulating variants, including XBB.1.5, EG.5.1, and FL.1.5.1. Moreover, NAb titers against all these variants were higher in vaccinated individuals with a history of XBB.1.5 infection compared with vaccinated individuals with no history of XBB.1.5 infection, suggesting the potential utility of the monovalent XBB.1.5 mRNA boosters.
Mesh-Begriff(e)	Humans ; COVID-19 ; SARS-CoV-2/genetics ; Antibodies, Neutralizing ; Immunization, Secondary ; Antibodies, Viral
Chemische Substanzen	Antibodies, Neutralizing ; Antibodies, Viral
Sprache	Englisch
Erscheinungsdatum	2023-10-21
Erscheinungsland	Netherlands
Dokumenttyp	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	605674-x
ISSN	1873-2518 ; 0264-410X
ISSN (online)	1873-2518
ISSN	0264-410X
DOI	10.1016/j.vaccine.2023.10.051
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Immunogenicity of BA.5 Bivalent mRNA Vaccine Boosters.

The New England journal of medicine

2023 Band 388, Heft 6, Seite(n) 565–567

Mesh-Begriff(e)	Humans ; Antibodies, Neutralizing ; Antibodies, Viral ; Vaccines, Combined/immunology ; Vaccines, Combined/therapeutic use ; Vaccines, Synthetic/immunology ; Vaccines, Synthetic/therapeutic use ; Immunogenicity, Vaccine/immunology ; COVID-19/genetics ; COVID-19/immunology ; COVID-19/prevention & control ; COVID-19/virology ; mRNA Vaccines
Chemische Substanzen	Antibodies, Neutralizing ; Antibodies, Viral ; Vaccines, Combined ; Vaccines, Synthetic
Sprache	Englisch
Erscheinungsdatum	2023-01-11
Erscheinungsland	United States
Dokumenttyp	Letter ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	207154-x
ISSN	1533-4406 ; 0028-4793
ISSN (online)	1533-4406
ISSN	0028-4793
DOI	10.1056/NEJMc2213948
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel: Waning Immunity Against XBB.1.5 Following Bivalent mRNA Boosters.

Lasrado, Ninaad / Collier, Ai-Ris Y / Miller, Jessica / Hachmann, Nicole P / Liu, Jinyan / Sciacca, Michaela / Wu, Cindy / Anand, Trisha / Bondzie, Esther A / Fisher, Jana L / Mazurek, Camille R / Patio, Robert C / Powers, Olivia / Rodrigues, Stefanie L / Rowe, Marjorie / Surve, Nehalee / Ty, Darren M / Korber, Bette / Barouch, Dan H

bioRxiv : the preprint server for biology

2023

Abstract: The SARS-CoV-2 Omicron variant has continued to evolve. XBB is a recombinant between two BA.2 sublineages, XBB.1 includes the G252V mutation, and XBB.1.5 includes the G252V and F486P mutations. XBB.1.5 has rapidly increased in frequency and has become ... ...

Abstract	The SARS-CoV-2 Omicron variant has continued to evolve. XBB is a recombinant between two BA.2 sublineages, XBB.1 includes the G252V mutation, and XBB.1.5 includes the G252V and F486P mutations. XBB.1.5 has rapidly increased in frequency and has become the dominant virus in New England. The bivalent mRNA vaccine boosters have been shown to increase neutralizing antibody (NAb) titers to multiple variants, but the durability of these responses remains to be determined. We assessed humoral and cellular immune responses in 30 participants who received the bivalent mRNA boosters and performed assays at baseline prior to boosting, at week 3 after boosting, and at month 3 after boosting. Our data demonstrate that XBB.1.5 substantially escapes NAb responses but not T cell responses after bivalent mRNA boosting. NAb titers to XBB.1 and XBB.1.5 were similar, suggesting that the F486P mutation confers greater transmissibility but not increased immune escape. By month 3, NAb titers to XBB.1 and XBB.1.5 declined essentially to baseline levels prior to boosting, while NAb titers to other variants declined less strikingly.
Sprache	Englisch
Erscheinungsdatum	2023-01-23
Erscheinungsland	United States
Dokumenttyp	Preprint
DOI	10.1101/2023.01.22.525079
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Waning Immunity Against XBB.1.5 Following Bivalent mRNA Boosters

Lasrado, Ninaad / Collier, Ai-ris / Miller, Jessica / Hachmann, Nicole / Liu, Jinyan / Sciacca, Michaela / Wu, Cindy / Anand, Trisha / Bondzie, Esther / Fisher, Jana / Mazurek, Camille / Patio, Robert / Powers, Olivia / Rodrigues, Stefanie / Rowe, Marjorie / Surve, Nehalee / Ty, Darren / Korber, Bette / Barouch, Dan H.

bioRxiv

Abstract	The SARS-CoV-2 Omicron variant has continued to evolve. XBB is a recombinant between two BA.2 sublineages, XBB.1 includes the G252V mutation, and XBB.1.5 includes the G252V and F486P mutations. XBB.1.5 has rapidly increased in frequency and has become the dominant virus in New England. The bivalent mRNA vaccine boosters have been shown to increase neutralizing antibody (NAb) titers to multiple variants, but the durability of these responses remains to be determined. We assessed humoral and cellular immune responses in 30 participants who received the bivalent mRNA boosters and performed assays at baseline prior to boosting, at week 3 after boosting, and at month 3 after boosting. Our data demonstrate that XBB.1.5 substantially escapes NAb responses but not T cell responses after bivalent mRNA boosting. NAb titers to XBB.1 and XBB.1.5 were similar, suggesting that the F486P mutation confers greater transmissibility but not increased immune escape. By month 3, NAb titers to XBB.1 and XBB.1.5 declined essentially to baseline levels prior to boosting, while NAb titers to other variants declined less strikingly.
Schlagwörter	covid19
Sprache	Englisch
Erscheinungsdatum	2023-01-23
Verlag	Cold Spring Harbor Laboratory
Dokumenttyp	Artikel ; Online
DOI	10.1101/2023.01.22.525079
Datenquelle	COVID19

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Artikel ; Online: Neutralization Escape by SARS-CoV-2 Omicron Subvariant BA.2.86

Lasrado, Ninaad / Collier, Ai-ris / Hachmann, Nicole / Miller, Jessica / Rowe, Marjorie / Schonberg, Eleanor / Rodrigues, Stefanie / LaPiana, Austin / Patio, Robert / Anand, Trisha / Fisher, Jana / Mazurek, Camille / Guan, Ruoran / Wagh, Kshitij / Theiler, James / Korber, Bette / Barouch, Dan H.

bioRxiv

Abstract: The continued evolution of SARS-CoV-2 may lead to evasion of vaccine immunity and natural immunity. A highly mutated Omicron variant BA.2.86 has recently been identified with over 30 amino acid changes in Spike compared with BA.2 and XBB.1.5. As of ... ...

Abstract	The continued evolution of SARS-CoV-2 may lead to evasion of vaccine immunity and natural immunity. A highly mutated Omicron variant BA.2.86 has recently been identified with over 30 amino acid changes in Spike compared with BA.2 and XBB.1.5. As of September 4, 2023, BA.2.86 has been identified in 37 sequences from 10 countries, which is likely an underestimate due to limited surveillance. The ability of BA.2.86 to evade NAbs compared with other currently circulating Omicron variants remains unknown. Our data show that NAb responses to BA.2.86 were lower than to BA.2 but were comparable or slightly higher than to the current circulating recombinant variants XBB.1.5, XBB.1.16, EG.5, EG.5.1, and FL.1.5.1.
Schlagwörter	covid19
Sprache	Englisch
Erscheinungsdatum	2023-09-05
Verlag	Cold Spring Harbor Laboratory
Dokumenttyp	Artikel ; Online
DOI	10.1101/2023.09.04.556272
Datenquelle	COVID19

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Artikel ; Online: Substantial Neutralization Escape by the SARS-CoV-2 Omicron Variant BQ.1.1

Miller, Jessica / Hachmann, Nicole / Collier, Ai-ris / Lasrado, Ninaad / Mazurek, Camille / Patio, Robert / Powers, Olivia / Surve, Nehalee / Theiler, James / Korber, Bette / Barouch, Dan H.

bioRxiv

Abstract: Omicron BA.5 has been the globally dominant SARS-CoV-2 variant and has demonstrated substantial neutralization escape compared with prior variants. Additional Omicron variants have recently emerged, including BA.4.6, BF.7, BA.2.75.2, and BQ.1.1, all of ... ...

Abstract	Omicron BA.5 has been the globally dominant SARS-CoV-2 variant and has demonstrated substantial neutralization escape compared with prior variants. Additional Omicron variants have recently emerged, including BA.4.6, BF.7, BA.2.75.2, and BQ.1.1, all of which have the Spike R346T mutation. In particular, BQ.1.1 has rapidly increased in frequency, and BA.5 has recently declined to less than half of viruses in the United States. Our data demonstrate that BA.2.75.2 and BQ.1.1 escape NAbs induced by infection and vaccination more effectively than BA.5. BQ.1.1 NAb titers were lower than BA.5 NAb titers by a factor of 7 in two cohorts of individuals who received the monovalent or bivalent mRNA vaccine boosters. These findings provide the immunologic context for the rapid increase in BQ.1.1 prevalence in regions where BA.5 is dominant and have implications for both vaccine immunity and natural immunity.
Schlagwörter	covid19
Sprache	Englisch
Erscheinungsdatum	2022-11-02
Verlag	Cold Spring Harbor Laboratory
Dokumenttyp	Artikel ; Online
DOI	10.1101/2022.11.01.514722
Datenquelle	COVID19

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