SARS-CoV-2 Omicron-B.1.1.529 leads to widespread escape from neutralizing antibody responses

OPTIC consortium; ISARIC4C consortium; Wanwisa Dejnirattisai; Jiandong  Huo; Daming Zhou; Jiří Zahradník; Piyada Supasa; Chang Liu; Helen M.E. Duyvesteyn; Helen M. Ginn; Alexander J. Mentzer; Aekkachai Tuekprakhon; Rungtiwa Nutalai; Beibei Wang; Aiste Dijokaite; Suman Khan; Ori Avinoam; Mohammad Bahar; Donal Skelly; Sandra Adele; Sile Ann Johnson; Ali Amini; Thomas G. Ritter; Chris Mason; Christina Dold; Daniel Pan; Sara Assadi; Adam Bellass; Nicola Omo-Dare; David Koeckerling; Amy Flaxman; Daniel Jenkin; Parvinder K. Aley; Merryn Voysey; Sue Ann Costa Clemens; Felipe Gomes Naveca; Valdinete Nascimento; Fernanda Nascimento; Cristiano Fernandes da Costa; Paola Cristina Resende; Alex Pauvolid-Correa; Marilda M. Siqueira; Vicky Baillie; Natali Serafin; Gaurav Kwatra; Kelly Da Silva; Shabir A. Madhi; Marta C. Nunes; Tariq Malik; Peter J.M. Openshaw; J Kenneth  Baillie; Malcolm G. Semple

doi:10.1016/j.cell.2021.12.046

SARS-CoV-2 Omicron-B.1.1.529 leads to widespread escape from neutralizing antibody responses

OPTIC consortium, ISARIC4C consortium, Wanwisa Dejnirattisai, Jiandong Huo, Daming Zhou, Jiří Zahradník, Piyada Supasa, Chang Liu, Helen M.E. Duyvesteyn, Helen M. Ginn, Alexander J. Mentzer, Aekkachai Tuekprakhon, Rungtiwa Nutalai, Beibei Wang, Aiste Dijokaite, Suman Khan, Ori Avinoam, Mohammad Bahar, Donal Skelly, Sandra AdeleSile Ann Johnson, Ali Amini, Thomas G. Ritter, Chris Mason, Christina Dold, Daniel Pan, Sara Assadi, Adam Bellass, Nicola Omo-Dare, David Koeckerling, Amy Flaxman, Daniel Jenkin, Parvinder K. Aley, Merryn Voysey, Sue Ann Costa Clemens, Felipe Gomes Naveca, Valdinete Nascimento, Fernanda Nascimento, Cristiano Fernandes da Costa, Paola Cristina Resende, Alex Pauvolid-Correa, Marilda M. Siqueira, Vicky Baillie, Natali Serafin, Gaurav Kwatra, Kelly Da Silva, Shabir A. Madhi, Marta C. Nunes, Tariq Malik, Peter J.M. Openshaw, J Kenneth Baillie, Malcolm G. Semple

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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.

Original language	English
Pages (from-to)	467-484.e15
Number of pages	33
Journal	Cell
Volume	185
Issue number	3
Early online date	4 Jan 2022
DOIs	https://doi.org/10.1016/j.cell.2021.12.046
Publication status	Published - 3 Feb 2022

Bibliographical note

Acknowledgments:
This work was supported by the Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Science (CIFMS), China (grant number: 2018-I2M-2-002) to D.I.S. and G.R.S. We are also grateful for support from Schmidt Futures, the Red Avenue Foundation, and the Oak Foundation. G.R.S. was supported by the Wellcome Trust. H.M.E.D. and J.R. are supported by the Wellcome Trust (101122/Z/13/Z), D.I.S. and E.E.F. by the UKRI MRC (MR/N00065X/1). G.S. and J.Z. were supported by the Israel Science Foundation (grant no. 3814/19) within the KillCorona—Curbing Coronavirus Research Program and by the Ben B. and Joyce E. Eisenberg Foundation. D.I.S. and G.R.S. are Jenner Investigators. This is a contribution from the UK Instruct-ERIC Centre. A.J.M. is an NIHR-supported academic Clinical Lecturer. The convalescent sampling was supported by the Medical Research Council (grant MC_PC_19059) (awarded to the ISARIC-4C Consortium) (with a full contributor list available at https://isaric4c.net/about/authors/) and the National Institutes for Health and Oxford Biomedical Research Centre and an Oxfordshire Health Services Research Committee grant to A.J.M. OPTIC Consortium: Christopher Conlon, Alexandra Deeks, John Frater, Lisa Frending, Siobhan Gardiner, Anni Jämsén, Katie Jeffery, Tom Malone, Eloise Phillips, Lucy Rothwell, and Lizzie Stafford. The Wellcome Centre for Human Genetics is supported by the Wellcome Trust (grant 090532/Z/09/Z). The computational aspects of this research were supported by the Wellcome Trust Core award grant number 203141/Z/16/Z and the NIHR Oxford BRC. We thank the staff of the MRC Human Immunology Unit for access to their Biacore Facility. Access to beamline I03 at Diamond Light Source was under application lb27009. The Oxford Vaccine work was supported by UK Research and Innovation, Coalition for Epidemic Preparedness Innovations, National Institute for Health Research (NIHR), NIHR Oxford Biomedical Research Centre, Thames Valley, and South Midland’s NIHR Clinical Research Network. We thank the Oxford Protective T cell Immunology for COVID-19 (OPTIC) Clinical team for participant sample collection and the Oxford Immunology Network COVID-19 Response T cell Consortium for laboratory support. We acknowledge the rapid sharing of Victoria, B.1.1.7 and B.1.351, which was isolated by scientists within the National Infection Service at PHE Porton Down, and the B.1.617.2 virus was kindly provided Wendy Barclay and Thushan De Silva. We thank The Secretariat of National Surveillance, Ministry of Health Brazil for assistance in obtaining P.1 samples. This work was supported by the UK Department of Health and Social Care as part of the PITCH (Protective Immunity from T cells to COVID-19 in Health workers) consortium, the UK Coronavirus Immunology Consortium (UK-CIC), and the Huo Family Foundation. E.B. and P.K. are NIHR Senior Investigators and P.K. is funded by WT109965MA and NIH (U19 I082360). S.J.D. is funded by an NIHR Global Research Professorship (NIHR300791). D.S. is an NIHR academic clinical fellow. F.G.N. is a CNPq fellow and is supported by FAPEAM (PCTI- EmergeSaude/AM call 005/2020 and Rede Genômica de Vigilância em Saúde - REGESAM), Conselho Nacional de Desenvolvimento Científico e Tecnológico (403276/2020-9), and Inova Fiocruz/ Fundação Oswaldo Cruz (VPPCB-007- FIO-18-2-30 - Geração de conhecimento). The team at the University of Witwatersrand were supported by The Bill & Melinda Gates Foundation (grant number INV-016202). The views expressed in this article are those of the authors and not necessarily those of the National Health Service (NHS), the Department of Health and Social Care (DHSC), the National Institutes for Health Research (NIHR), the Medical Research Council (MRC), or Public Healtc, England.

Keywords

SARS-CoV-2
Omicron
variants
vaccines
immune evasion
receptor interaction
Spike
RBD

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DejnirattisaiW2022SARSFinal published version, 12 MBLicence: Creative Commons: Attribution (CC BY)

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OPTIC consortium, ISARIC4C consortium, Dejnirattisai, W., Huo, J., Zhou, D., Zahradník, J., Supasa, P., Liu, C., Duyvesteyn, H. M. E., Ginn, H. M., Mentzer, A. J., Tuekprakhon, A., Nutalai, R., Wang, B., Dijokaite, A., Khan, S., Avinoam, O., Bahar, M., Skelly, D., ... Semple, M. G. (2022). SARS-CoV-2 Omicron-B.1.1.529 leads to widespread escape from neutralizing antibody responses. Cell, 185(3), 467-484.e15. https://doi.org/10.1016/j.cell.2021.12.046

@article{0b82861b932e43ccbfe8a3f88af44924,

title = "SARS-CoV-2 Omicron-B.1.1.529 leads to widespread escape from neutralizing antibody responses",

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.",

keywords = "SARS-CoV-2, Omicron, variants, vaccines, immune evasion, receptor interaction, Spike, RBD",

author = "{OPTIC consortium} and {ISARIC4C consortium} and Wanwisa Dejnirattisai and Jiandong Huo and Daming Zhou and Ji{\v r}{\'i} Zahradn{\'i}k and Piyada Supasa and Chang Liu and Duyvesteyn, {Helen M.E.} and Ginn, {Helen M.} and Mentzer, {Alexander J.} and Aekkachai Tuekprakhon and Rungtiwa Nutalai and Beibei Wang and Aiste Dijokaite and Suman Khan and Ori Avinoam and Mohammad Bahar and Donal Skelly and Sandra Adele and Johnson, {Sile Ann} and Ali Amini and Ritter, {Thomas G.} and Chris Mason and Christina Dold and Daniel Pan and Sara Assadi and Adam Bellass and Nicola Omo-Dare and David Koeckerling and Amy Flaxman and Daniel Jenkin and Aley, {Parvinder K.} and Merryn Voysey and Clemens, {Sue Ann Costa} and Naveca, {Felipe Gomes} and Valdinete Nascimento and Fernanda Nascimento and {da Costa}, {Cristiano Fernandes} and Resende, {Paola Cristina} and Alex Pauvolid-Correa and Siqueira, {Marilda M.} and Vicky Baillie and Natali Serafin and Gaurav Kwatra and {Da Silva}, Kelly and Madhi, {Shabir A.} and Nunes, {Marta C.} and Tariq Malik and Openshaw, {Peter J.M.} and Baillie, {J Kenneth} and Semple, {Malcolm G.} and Christopher Green",

note = "Acknowledgments: This work was supported by the Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Science (CIFMS), China (grant number: 2018-I2M-2-002) to D.I.S. and G.R.S. We are also grateful for support from Schmidt Futures, the Red Avenue Foundation, and the Oak Foundation. G.R.S. was supported by the Wellcome Trust. H.M.E.D. and J.R. are supported by the Wellcome Trust (101122/Z/13/Z), D.I.S. and E.E.F. by the UKRI MRC (MR/N00065X/1). G.S. and J.Z. were supported by the Israel Science Foundation (grant no. 3814/19) within the KillCorona—Curbing Coronavirus Research Program and by the Ben B. and Joyce E. Eisenberg Foundation. D.I.S. and G.R.S. are Jenner Investigators. This is a contribution from the UK Instruct-ERIC Centre. A.J.M. is an NIHR-supported academic Clinical Lecturer. The convalescent sampling was supported by the Medical Research Council (grant MC_PC_19059) (awarded to the ISARIC-4C Consortium) (with a full contributor list available at https://isaric4c.net/about/authors/) and the National Institutes for Health and Oxford Biomedical Research Centre and an Oxfordshire Health Services Research Committee grant to A.J.M. OPTIC Consortium: Christopher Conlon, Alexandra Deeks, John Frater, Lisa Frending, Siobhan Gardiner, Anni J{\"a}ms{\'e}n, Katie Jeffery, Tom Malone, Eloise Phillips, Lucy Rothwell, and Lizzie Stafford. The Wellcome Centre for Human Genetics is supported by the Wellcome Trust (grant 090532/Z/09/Z). The computational aspects of this research were supported by the Wellcome Trust Core award grant number 203141/Z/16/Z and the NIHR Oxford BRC. We thank the staff of the MRC Human Immunology Unit for access to their Biacore Facility. Access to beamline I03 at Diamond Light Source was under application lb27009. The Oxford Vaccine work was supported by UK Research and Innovation, Coalition for Epidemic Preparedness Innovations, National Institute for Health Research (NIHR), NIHR Oxford Biomedical Research Centre, Thames Valley, and South Midland{\textquoteright}s NIHR Clinical Research Network. We thank the Oxford Protective T cell Immunology for COVID-19 (OPTIC) Clinical team for participant sample collection and the Oxford Immunology Network COVID-19 Response T cell Consortium for laboratory support. We acknowledge the rapid sharing of Victoria, B.1.1.7 and B.1.351, which was isolated by scientists within the National Infection Service at PHE Porton Down, and the B.1.617.2 virus was kindly provided Wendy Barclay and Thushan De Silva. We thank The Secretariat of National Surveillance, Ministry of Health Brazil for assistance in obtaining P.1 samples. This work was supported by the UK Department of Health and Social Care as part of the PITCH (Protective Immunity from T cells to COVID-19 in Health workers) consortium, the UK Coronavirus Immunology Consortium (UK-CIC), and the Huo Family Foundation. E.B. and P.K. are NIHR Senior Investigators and P.K. is funded by WT109965MA and NIH (U19 I082360). S.J.D. is funded by an NIHR Global Research Professorship (NIHR300791). D.S. is an NIHR academic clinical fellow. F.G.N. is a CNPq fellow and is supported by FAPEAM (PCTI- EmergeSaude/AM call 005/2020 and Rede Gen{\^o}mica de Vigil{\^a}ncia em Sa{\'u}de - REGESAM), Conselho Nacional de Desenvolvimento Cient{\'i}fico e Tecnol{\'o}gico (403276/2020-9), and Inova Fiocruz/ Funda{\c c}{\~a}o Oswaldo Cruz (VPPCB-007- FIO-18-2-30 - Gera{\c c}{\~a}o de conhecimento). The team at the University of Witwatersrand were supported by The Bill & Melinda Gates Foundation (grant number INV-016202). The views expressed in this article are those of the authors and not necessarily those of the National Health Service (NHS), the Department of Health and Social Care (DHSC), the National Institutes for Health Research (NIHR), the Medical Research Council (MRC), or Public Healtc, England.",

year = "2022",

month = feb,

day = "3",

doi = "10.1016/j.cell.2021.12.046",

language = "English",

volume = "185",

pages = "467--484.e15",

journal = "Cell",

issn = "0092-8674",

publisher = "Elsevier",

number = "3",

}

OPTIC consortium, ISARIC4C consortium, Dejnirattisai, W, Huo, J, Zhou, D, Zahradník, J, Supasa, P, Liu, C, Duyvesteyn, HME, Ginn, HM, Mentzer, AJ, Tuekprakhon, A, Nutalai, R, Wang, B, Dijokaite, A, Khan, S, Avinoam, O, Bahar, M, Skelly, D, Adele, S, Johnson, SA, Amini, A, Ritter, TG, Mason, C, Dold, C, Pan, D, Assadi, S, Bellass, A, Omo-Dare, N, Koeckerling, D, Flaxman, A, Jenkin, D, Aley, PK, Voysey, M, Clemens, SAC, Naveca, FG, Nascimento, V, Nascimento, F, da Costa, CF, Resende, PC, Pauvolid-Correa, A, Siqueira, MM, Baillie, V, Serafin, N, Kwatra, G, Da Silva, K, Madhi, SA, Nunes, MC, Malik, T, Openshaw, PJM, Baillie, JK & Semple, MG 2022, 'SARS-CoV-2 Omicron-B.1.1.529 leads to widespread escape from neutralizing antibody responses', Cell, vol. 185, no. 3, pp. 467-484.e15. https://doi.org/10.1016/j.cell.2021.12.046

TY - JOUR

T1 - SARS-CoV-2 Omicron-B.1.1.529 leads to widespread escape from neutralizing antibody responses

AU - OPTIC consortium

AU - ISARIC4C consortium

AU - Dejnirattisai, Wanwisa

AU - Huo, Jiandong

AU - Zhou, Daming

AU - Zahradník, Jiří

AU - Supasa, Piyada

AU - Liu, Chang

AU - Duyvesteyn, Helen M.E.

AU - Ginn, Helen M.

AU - Mentzer, Alexander J.

AU - Tuekprakhon, Aekkachai

AU - Nutalai, Rungtiwa

AU - Wang, Beibei

AU - Dijokaite, Aiste

AU - Khan, Suman

AU - Avinoam, Ori

AU - Bahar, Mohammad

AU - Skelly, Donal

AU - Adele, Sandra

AU - Johnson, Sile Ann

AU - Amini, Ali

AU - Ritter, Thomas G.

AU - Mason, Chris

AU - Dold, Christina

AU - Pan, Daniel

AU - Assadi, Sara

AU - Bellass, Adam

AU - Omo-Dare, Nicola

AU - Koeckerling, David

AU - Flaxman, Amy

AU - Jenkin, Daniel

AU - Aley, Parvinder K.

AU - Voysey, Merryn

AU - Clemens, Sue Ann Costa

AU - Naveca, Felipe Gomes

AU - Nascimento, Valdinete

AU - Nascimento, Fernanda

AU - da Costa, Cristiano Fernandes

AU - Resende, Paola Cristina

AU - Pauvolid-Correa, Alex

AU - Siqueira, Marilda M.

AU - Baillie, Vicky

AU - Serafin, Natali

AU - Kwatra, Gaurav

AU - Da Silva, Kelly

AU - Madhi, Shabir A.

AU - Nunes, Marta C.

AU - Malik, Tariq

AU - Openshaw, Peter J.M.

AU - Baillie, J Kenneth

AU - Semple, Malcolm G.

AU - Green, Christopher

N1 - Acknowledgments: This work was supported by the Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Science (CIFMS), China (grant number: 2018-I2M-2-002) to D.I.S. and G.R.S. We are also grateful for support from Schmidt Futures, the Red Avenue Foundation, and the Oak Foundation. G.R.S. was supported by the Wellcome Trust. H.M.E.D. and J.R. are supported by the Wellcome Trust (101122/Z/13/Z), D.I.S. and E.E.F. by the UKRI MRC (MR/N00065X/1). G.S. and J.Z. were supported by the Israel Science Foundation (grant no. 3814/19) within the KillCorona—Curbing Coronavirus Research Program and by the Ben B. and Joyce E. Eisenberg Foundation. D.I.S. and G.R.S. are Jenner Investigators. This is a contribution from the UK Instruct-ERIC Centre. A.J.M. is an NIHR-supported academic Clinical Lecturer. The convalescent sampling was supported by the Medical Research Council (grant MC_PC_19059) (awarded to the ISARIC-4C Consortium) (with a full contributor list available at https://isaric4c.net/about/authors/) and the National Institutes for Health and Oxford Biomedical Research Centre and an Oxfordshire Health Services Research Committee grant to A.J.M. OPTIC Consortium: Christopher Conlon, Alexandra Deeks, John Frater, Lisa Frending, Siobhan Gardiner, Anni Jämsén, Katie Jeffery, Tom Malone, Eloise Phillips, Lucy Rothwell, and Lizzie Stafford. The Wellcome Centre for Human Genetics is supported by the Wellcome Trust (grant 090532/Z/09/Z). The computational aspects of this research were supported by the Wellcome Trust Core award grant number 203141/Z/16/Z and the NIHR Oxford BRC. We thank the staff of the MRC Human Immunology Unit for access to their Biacore Facility. Access to beamline I03 at Diamond Light Source was under application lb27009. The Oxford Vaccine work was supported by UK Research and Innovation, Coalition for Epidemic Preparedness Innovations, National Institute for Health Research (NIHR), NIHR Oxford Biomedical Research Centre, Thames Valley, and South Midland’s NIHR Clinical Research Network. We thank the Oxford Protective T cell Immunology for COVID-19 (OPTIC) Clinical team for participant sample collection and the Oxford Immunology Network COVID-19 Response T cell Consortium for laboratory support. We acknowledge the rapid sharing of Victoria, B.1.1.7 and B.1.351, which was isolated by scientists within the National Infection Service at PHE Porton Down, and the B.1.617.2 virus was kindly provided Wendy Barclay and Thushan De Silva. We thank The Secretariat of National Surveillance, Ministry of Health Brazil for assistance in obtaining P.1 samples. This work was supported by the UK Department of Health and Social Care as part of the PITCH (Protective Immunity from T cells to COVID-19 in Health workers) consortium, the UK Coronavirus Immunology Consortium (UK-CIC), and the Huo Family Foundation. E.B. and P.K. are NIHR Senior Investigators and P.K. is funded by WT109965MA and NIH (U19 I082360). S.J.D. is funded by an NIHR Global Research Professorship (NIHR300791). D.S. is an NIHR academic clinical fellow. F.G.N. is a CNPq fellow and is supported by FAPEAM (PCTI- EmergeSaude/AM call 005/2020 and Rede Genômica de Vigilância em Saúde - REGESAM), Conselho Nacional de Desenvolvimento Científico e Tecnológico (403276/2020-9), and Inova Fiocruz/ Fundação Oswaldo Cruz (VPPCB-007- FIO-18-2-30 - Geração de conhecimento). The team at the University of Witwatersrand were supported by The Bill & Melinda Gates Foundation (grant number INV-016202). The views expressed in this article are those of the authors and not necessarily those of the National Health Service (NHS), the Department of Health and Social Care (DHSC), the National Institutes for Health Research (NIHR), the Medical Research Council (MRC), or Public Healtc, England.

PY - 2022/2/3

Y1 - 2022/2/3

N2 - 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.

AB - 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.

KW - SARS-CoV-2

KW - Omicron

KW - variants

KW - vaccines

KW - immune evasion

KW - receptor interaction

KW - Spike

KW - RBD

U2 - 10.1016/j.cell.2021.12.046

DO - 10.1016/j.cell.2021.12.046

M3 - Article

SN - 0092-8674

VL - 185

SP - 467-484.e15

JO - Cell

JF - Cell

IS - 3

ER -

SARS-CoV-2 Omicron-B.1.1.529 leads to widespread escape from neutralizing antibody responses

Abstract

Bibliographical note

Keywords

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