Rapid decline in vaccine-boosted neutralizing antibodies against SARS-CoV-2 Omicron variant

the DMID 21-0012 Study Group

doi:10.1016/j.xcrm.2022.100679

Rapid decline in vaccine-boosted neutralizing antibodies against SARS-CoV-2 Omicron variant

the DMID 21-0012 Study Group

Research output: Contribution to journal › Article › peer-review

71 Scopus citations

Abstract

The Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exhibits reduced susceptibility to vaccine-induced neutralizing antibodies, requiring a boost to generate protective immunity. We assess the magnitude and short-term durability of neutralizing antibodies after homologous and heterologous boosting with mRNA and Ad26.COV2.S vaccines. All prime-boost combinations substantially increase the neutralization titers to Omicron, although the boosted titers decline rapidly within 2 months from the peak response compared with boosted titers against the prototypic D614G variant. Boosted Omicron neutralization titers are substantially higher for homologous mRNA vaccine boosting, and for heterologous mRNA and Ad26.COV2.S vaccine boosting, compared with homologous Ad26.COV2.S boosting. Homologous mRNA vaccine boosting generates nearly equivalent neutralizing activity against Omicron sublineages BA.1, BA.2, and BA.3 but modestly reduced neutralizing activity against BA.2.12.1 and BA.4/BA.5 compared with BA.1. These results have implications for boosting requirements to protect against Omicron and future variants of SARS-CoV-2. This trial was conducted under ClincalTrials.gov: NCT04889209.

Original language	English (US)
Article number	100679
Journal	Cell Reports Medicine
Volume	3
Issue number	7
DOIs	https://doi.org/10.1016/j.xcrm.2022.100679
State	Published - Jul 19 2022
Externally published	Yes

Keywords

BA.2.12.1
BA.4/BA.5
COVID-19
Omicron variant
SARS-CoV-2
booster
mRNA vaccine
neutralizing antibody
recombinant adenovirus vaccine
sublineage

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)

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10.1016/j.xcrm.2022.100679

Cite this

@article{ff7982e79a1a45d1ac9bd5b8dabeea47,

title = "Rapid decline in vaccine-boosted neutralizing antibodies against SARS-CoV-2 Omicron variant",

abstract = "The Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exhibits reduced susceptibility to vaccine-induced neutralizing antibodies, requiring a boost to generate protective immunity. We assess the magnitude and short-term durability of neutralizing antibodies after homologous and heterologous boosting with mRNA and Ad26.COV2.S vaccines. All prime-boost combinations substantially increase the neutralization titers to Omicron, although the boosted titers decline rapidly within 2 months from the peak response compared with boosted titers against the prototypic D614G variant. Boosted Omicron neutralization titers are substantially higher for homologous mRNA vaccine boosting, and for heterologous mRNA and Ad26.COV2.S vaccine boosting, compared with homologous Ad26.COV2.S boosting. Homologous mRNA vaccine boosting generates nearly equivalent neutralizing activity against Omicron sublineages BA.1, BA.2, and BA.3 but modestly reduced neutralizing activity against BA.2.12.1 and BA.4/BA.5 compared with BA.1. These results have implications for boosting requirements to protect against Omicron and future variants of SARS-CoV-2. This trial was conducted under ClincalTrials.gov: NCT04889209.",

keywords = "BA.2.12.1, BA.4/BA.5, COVID-19, Omicron variant, SARS-CoV-2, booster, mRNA vaccine, neutralizing antibody, recombinant adenovirus vaccine, sublineage",

author = "{the DMID 21-0012 Study Group} and Lyke, {Kirsten E.} and Atmar, {Robert L.} and Islas, {Clara Dominguez} and Posavad, {Christine M.} and Daniel Szydlo and {Paul Chourdhury}, Rahul and Deming, {Meagan E.} and Amanda Eaton and Jackson, {Lisa A.} and Branche, {Angela R.} and {El Sahly}, {Hana M.} and Rostad, {Christina A.} and Martin, {Judith M.} and Christine Johnston and Rupp, {Richard E.} and Mulligan, {Mark J.} and Brady, {Rebecca C.} and Frenck, {Robert W.} and Mart{\'i}n B{\"a}cker and Kottkamp, {Angelica C.} and Babu, {Tara M.} and Kumaravel Rajakumar and Srilatha Edupuganti and David Dobrzynski and Coler, {Rhea N.} and Archer, {Janet I.} and Sonja Crandon and Zemanek, {Jillian A.} and Brown, {Elizabeth R.} and Neuzil, {Kathleen M.} and Stephens, {David S.} and Post, {Diane J.} and Nayak, {Seema U.} and Suthar, {Mehul S.} and Roberts, {Paul C.} and Beigel, {John H.} and Montefiori, {David C.} and Husson, {Jennifer S.} and Angie Price and Whitaker, {Jennifer A.} and Keitel, {Wendy A.} and Falsey, {Ann R.} and Ian Shannon and Daniel Graciaa and Nadine Rouphael and Anderson, {Evan J.} and Satoshi Kamidani and Muniz, {Gysella B.} and Sonika Bhatnagar and Laura Porterfield",

note = "Funding Information: The trial was sponsored and primarily funded by the Infectious Diseases Clinical Research Consortium through the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under award numbers UM1AI48372 , UM1AI148373 , UM1AI148450 , UM1AI148452 , UM1AI148573 , UM1AI148574 , UM1AI148575 , UM1AI148576 , UM1AI148684 , and UM1 AI148689 and with support from the NIAID Collaborative Influenza Vaccine Innovation Centers (CIVICs) contract 75N93019C00050 and NIH Vaccine Research Center . Funding for the Suthar laboratory included the following: NIH P51 OD011132 , 3U19AI057266-17S1 , 1U54CA260563 , and HHSN272201400004C , NIH/NIAID CEIRR under contract 75N93021C00017 to Emory University from NIAID and Emory School of Medicine , and Woodruff Health Sciences Center 2020 COVID-19 CURE Award. We would like to acknowledge Moderna, Inc., Johnson & Johnson/Janssen, and Pfizer/BioNTech Pharmaceuticals for their collaboration, scientific input, and sharing of documents needed to implement this trial. All products were acquired through the government procurement process. Funding Information: The trial was sponsored and primarily funded by the Infectious Diseases Clinical Research Consortium through the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under award numbers UM1AI48372, UM1AI148373, UM1AI148450, UM1AI148452, UM1AI148573, UM1AI148574, UM1AI148575, UM1AI148576, UM1AI148684, and UM1 AI148689 and with support from the NIAID Collaborative Influenza Vaccine Innovation Centers (CIVICs) contract 75N93019C00050 and NIH Vaccine Research Center. Funding for the Suthar laboratory included the following: NIH P51 OD011132, 3U19AI057266-17S1, 1U54CA260563, and HHSN272201400004C, NIH/NIAID CEIRR under contract 75N93021C00017 to Emory University from NIAID and Emory School of Medicine, and Woodruff Health Sciences Center 2020 COVID-19 CURE Award. We would like to acknowledge Moderna, Inc. Johnson & Johnson/Janssen, and Pfizer/BioNTech Pharmaceuticals for their collaboration, scientific input, and sharing of documents needed to implement this trial. All products were acquired through the government procurement process. Conceptualization, K.E.L. R.L.A. P.C.R. J.H.B. and D.C.M.; methodology, C.D.I. D.S. P.C.R. M.S.S. and D.C.M.; data curation, J.A.Z.; investigation, K.E.L. R.L.A. R.C.P. M.E.D. A.E. L.A.J. A.R.B. H.M.E.S. C.A.R. J.M.M. C.J. R.E.R. M.J.M. R.C.B. R.W.F. M.B. A.C.K. T.M.B. K.R. S.E. D.D. R.N.C. M.S.S. and D.C.M.; writing – original draft, K.E.L. R.L.A. S.D.I. M.S.S. P.C.R. J.H.B. and D.C.M.; formal analysis and visualization, C.D.I. D.S. and E.R.B.; funding acquisition, S.U.N. P.C.R. K.M.N. D.S.S. and J.H.B.; resources, C.M.P. M.S.S. P.C.R. and D.C.M.; project administration, J.I.A. and S.C.; supervision, K.M.N. D.S.S. P.C.R. A.E. J.H.B. M.S.S. and D.C.M. R.L.A. C.D.I. C.M.P. D.S. R.P.C. M.E.D. A.E. H.M.E.S. R.E.R. M.B. A.C.K. T.M.B. D.D. R.N.C. J.I.A. S.C. J.A.Z. S.U.N. E.R.B. and D.J.P. report no competing interests. K.E.L. receives grant awards from Pfizer, Inc. COVID-19 vaccine research. L.A.J.{\textquoteright}s institution receives grant funding from NIH and CDC for vaccine-related assessments, including those of COVID-19 vaccines. A.R.B. has grant funding from Pfizer, Janssen, Merck, and Cyanvac for non-COVID-19-related work and serves as a consultant for GSK and Janssen. C.A.R.'s institution has received funds to conduct clinical research from the National Institutes of Health, CDC, BioFire, Inc. Genentech, GSK, Janssen, MedImmune, Merck, Micron, Moderna, Novavax, PaxVax, Pfizer, Regeneron, and Sanofi-Pasteur. She is co-inventor of patented RSV vaccine technology, which has been licensed to Meissa Vaccines, Inc. J.M.M. has served as a consultant for Merck, Sharp, and Dohme for non-Covid-related work. C.J. receives funding from the Bill and Melinda Gates Foundation, NIH, and CDC, consults for Gilead and Abbvie, serves on a DSMB for MedPace, and receives royalties from UpToDate. M.J.M. has laboratory research and clinical trials contracts for vaccines or MAB versus SARS-CoV-2 with Lilly, Pfizer (exclusive of the current work), and Sanofi and personal fees for Scientific Advisory Board service from Merck, Meissa Vaccines, Inc. and Pfizer. R.C.B. receives funding for vaccine trials from Path Nipah and Pfizer. R.W.F. receives funding to perform clinical trials from Pfizer, Moderna, Astra Zeneca, and Emergent Health, and he serves on advisory boards for Johnson & Johnson, Merck, Sanofi Pasteur, and Seqirus. S.E. receives funding to her institution from Sanofi Pasteur for a non-COVID-19 vaccine study. K.M.N. holds a grant from Pfizer, without salary support, for a COVID-19 vaccine study and salary support from the National Institutes of Health (NIH) for work on multiple COVID-19 vaccine trials. D.S.S. is supported by grant awards from NIH/NIAID. P.C.R. and J.H.B. report a pending US patent application no. 63/025918 entitled “Coronavirus RNA vaccines and methods of use.” D.C.M. receives funding from NIH and Moderna for laboratory studies of COVID-19 vaccine antibody responses. M.S.S. receives funding from Moderna, Inc. and Ocugen. D.C.M. receives funding from Moderna, Inc. We worked to ensure gender balance in the recruitment of human subjects. We worked to ensure ethnic or other types of diversity in the recruitment of human subjects. The author list of this paper includes contributors from the location where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work. Funding Information: The clinical trial was sponsored by the Infectious Diseases Clinical Research Consortium through the National Institute for Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH) as protocol DMID 21-0012 and registered as ClinicalTrials.gov # NCT04889209. Publisher Copyright: {\textcopyright} 2022 The Authors",

year = "2022",

month = jul,

day = "19",

doi = "10.1016/j.xcrm.2022.100679",

language = "English (US)",

volume = "3",

journal = "Cell Reports Medicine",

issn = "2666-3791",

publisher = "Cell Press",

number = "7",

}

TY - JOUR

T1 - Rapid decline in vaccine-boosted neutralizing antibodies against SARS-CoV-2 Omicron variant

AU - the DMID 21-0012 Study Group

AU - Lyke, Kirsten E.

AU - Atmar, Robert L.

AU - Islas, Clara Dominguez

AU - Posavad, Christine M.

AU - Szydlo, Daniel

AU - Paul Chourdhury, Rahul

AU - Deming, Meagan E.

AU - Eaton, Amanda

AU - Jackson, Lisa A.

AU - Branche, Angela R.

AU - El Sahly, Hana M.

AU - Rostad, Christina A.

AU - Martin, Judith M.

AU - Johnston, Christine

AU - Rupp, Richard E.

AU - Mulligan, Mark J.

AU - Brady, Rebecca C.

AU - Frenck, Robert W.

AU - Bäcker, Martín

AU - Kottkamp, Angelica C.

AU - Babu, Tara M.

AU - Rajakumar, Kumaravel

AU - Edupuganti, Srilatha

AU - Dobrzynski, David

AU - Coler, Rhea N.

AU - Archer, Janet I.

AU - Crandon, Sonja

AU - Zemanek, Jillian A.

AU - Brown, Elizabeth R.

AU - Neuzil, Kathleen M.

AU - Stephens, David S.

AU - Post, Diane J.

AU - Nayak, Seema U.

AU - Suthar, Mehul S.

AU - Roberts, Paul C.

AU - Beigel, John H.

AU - Montefiori, David C.

AU - Husson, Jennifer S.

AU - Price, Angie

AU - Whitaker, Jennifer A.

AU - Keitel, Wendy A.

AU - Falsey, Ann R.

AU - Shannon, Ian

AU - Graciaa, Daniel

AU - Rouphael, Nadine

AU - Anderson, Evan J.

AU - Kamidani, Satoshi

AU - Muniz, Gysella B.

AU - Bhatnagar, Sonika

AU - Porterfield, Laura

N1 - Funding Information: The trial was sponsored and primarily funded by the Infectious Diseases Clinical Research Consortium through the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under award numbers UM1AI48372 , UM1AI148373 , UM1AI148450 , UM1AI148452 , UM1AI148573 , UM1AI148574 , UM1AI148575 , UM1AI148576 , UM1AI148684 , and UM1 AI148689 and with support from the NIAID Collaborative Influenza Vaccine Innovation Centers (CIVICs) contract 75N93019C00050 and NIH Vaccine Research Center . Funding for the Suthar laboratory included the following: NIH P51 OD011132 , 3U19AI057266-17S1 , 1U54CA260563 , and HHSN272201400004C , NIH/NIAID CEIRR under contract 75N93021C00017 to Emory University from NIAID and Emory School of Medicine , and Woodruff Health Sciences Center 2020 COVID-19 CURE Award. We would like to acknowledge Moderna, Inc., Johnson & Johnson/Janssen, and Pfizer/BioNTech Pharmaceuticals for their collaboration, scientific input, and sharing of documents needed to implement this trial. All products were acquired through the government procurement process. Funding Information: The trial was sponsored and primarily funded by the Infectious Diseases Clinical Research Consortium through the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under award numbers UM1AI48372, UM1AI148373, UM1AI148450, UM1AI148452, UM1AI148573, UM1AI148574, UM1AI148575, UM1AI148576, UM1AI148684, and UM1 AI148689 and with support from the NIAID Collaborative Influenza Vaccine Innovation Centers (CIVICs) contract 75N93019C00050 and NIH Vaccine Research Center. Funding for the Suthar laboratory included the following: NIH P51 OD011132, 3U19AI057266-17S1, 1U54CA260563, and HHSN272201400004C, NIH/NIAID CEIRR under contract 75N93021C00017 to Emory University from NIAID and Emory School of Medicine, and Woodruff Health Sciences Center 2020 COVID-19 CURE Award. We would like to acknowledge Moderna, Inc. Johnson & Johnson/Janssen, and Pfizer/BioNTech Pharmaceuticals for their collaboration, scientific input, and sharing of documents needed to implement this trial. All products were acquired through the government procurement process. Conceptualization, K.E.L. R.L.A. P.C.R. J.H.B. and D.C.M.; methodology, C.D.I. D.S. P.C.R. M.S.S. and D.C.M.; data curation, J.A.Z.; investigation, K.E.L. R.L.A. R.C.P. M.E.D. A.E. L.A.J. A.R.B. H.M.E.S. C.A.R. J.M.M. C.J. R.E.R. M.J.M. R.C.B. R.W.F. M.B. A.C.K. T.M.B. K.R. S.E. D.D. R.N.C. M.S.S. and D.C.M.; writing – original draft, K.E.L. R.L.A. S.D.I. M.S.S. P.C.R. J.H.B. and D.C.M.; formal analysis and visualization, C.D.I. D.S. and E.R.B.; funding acquisition, S.U.N. P.C.R. K.M.N. D.S.S. and J.H.B.; resources, C.M.P. M.S.S. P.C.R. and D.C.M.; project administration, J.I.A. and S.C.; supervision, K.M.N. D.S.S. P.C.R. A.E. J.H.B. M.S.S. and D.C.M. R.L.A. C.D.I. C.M.P. D.S. R.P.C. M.E.D. A.E. H.M.E.S. R.E.R. M.B. A.C.K. T.M.B. D.D. R.N.C. J.I.A. S.C. J.A.Z. S.U.N. E.R.B. and D.J.P. report no competing interests. K.E.L. receives grant awards from Pfizer, Inc. COVID-19 vaccine research. L.A.J.’s institution receives grant funding from NIH and CDC for vaccine-related assessments, including those of COVID-19 vaccines. A.R.B. has grant funding from Pfizer, Janssen, Merck, and Cyanvac for non-COVID-19-related work and serves as a consultant for GSK and Janssen. C.A.R.'s institution has received funds to conduct clinical research from the National Institutes of Health, CDC, BioFire, Inc. Genentech, GSK, Janssen, MedImmune, Merck, Micron, Moderna, Novavax, PaxVax, Pfizer, Regeneron, and Sanofi-Pasteur. She is co-inventor of patented RSV vaccine technology, which has been licensed to Meissa Vaccines, Inc. J.M.M. has served as a consultant for Merck, Sharp, and Dohme for non-Covid-related work. C.J. receives funding from the Bill and Melinda Gates Foundation, NIH, and CDC, consults for Gilead and Abbvie, serves on a DSMB for MedPace, and receives royalties from UpToDate. M.J.M. has laboratory research and clinical trials contracts for vaccines or MAB versus SARS-CoV-2 with Lilly, Pfizer (exclusive of the current work), and Sanofi and personal fees for Scientific Advisory Board service from Merck, Meissa Vaccines, Inc. and Pfizer. R.C.B. receives funding for vaccine trials from Path Nipah and Pfizer. R.W.F. receives funding to perform clinical trials from Pfizer, Moderna, Astra Zeneca, and Emergent Health, and he serves on advisory boards for Johnson & Johnson, Merck, Sanofi Pasteur, and Seqirus. S.E. receives funding to her institution from Sanofi Pasteur for a non-COVID-19 vaccine study. K.M.N. holds a grant from Pfizer, without salary support, for a COVID-19 vaccine study and salary support from the National Institutes of Health (NIH) for work on multiple COVID-19 vaccine trials. D.S.S. is supported by grant awards from NIH/NIAID. P.C.R. and J.H.B. report a pending US patent application no. 63/025918 entitled “Coronavirus RNA vaccines and methods of use.” D.C.M. receives funding from NIH and Moderna for laboratory studies of COVID-19 vaccine antibody responses. M.S.S. receives funding from Moderna, Inc. and Ocugen. D.C.M. receives funding from Moderna, Inc. We worked to ensure gender balance in the recruitment of human subjects. We worked to ensure ethnic or other types of diversity in the recruitment of human subjects. The author list of this paper includes contributors from the location where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work. Funding Information: The clinical trial was sponsored by the Infectious Diseases Clinical Research Consortium through the National Institute for Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH) as protocol DMID 21-0012 and registered as ClinicalTrials.gov # NCT04889209. Publisher Copyright: © 2022 The Authors

PY - 2022/7/19

Y1 - 2022/7/19

N2 - The Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exhibits reduced susceptibility to vaccine-induced neutralizing antibodies, requiring a boost to generate protective immunity. We assess the magnitude and short-term durability of neutralizing antibodies after homologous and heterologous boosting with mRNA and Ad26.COV2.S vaccines. All prime-boost combinations substantially increase the neutralization titers to Omicron, although the boosted titers decline rapidly within 2 months from the peak response compared with boosted titers against the prototypic D614G variant. Boosted Omicron neutralization titers are substantially higher for homologous mRNA vaccine boosting, and for heterologous mRNA and Ad26.COV2.S vaccine boosting, compared with homologous Ad26.COV2.S boosting. Homologous mRNA vaccine boosting generates nearly equivalent neutralizing activity against Omicron sublineages BA.1, BA.2, and BA.3 but modestly reduced neutralizing activity against BA.2.12.1 and BA.4/BA.5 compared with BA.1. These results have implications for boosting requirements to protect against Omicron and future variants of SARS-CoV-2. This trial was conducted under ClincalTrials.gov: NCT04889209.

AB - The Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exhibits reduced susceptibility to vaccine-induced neutralizing antibodies, requiring a boost to generate protective immunity. We assess the magnitude and short-term durability of neutralizing antibodies after homologous and heterologous boosting with mRNA and Ad26.COV2.S vaccines. All prime-boost combinations substantially increase the neutralization titers to Omicron, although the boosted titers decline rapidly within 2 months from the peak response compared with boosted titers against the prototypic D614G variant. Boosted Omicron neutralization titers are substantially higher for homologous mRNA vaccine boosting, and for heterologous mRNA and Ad26.COV2.S vaccine boosting, compared with homologous Ad26.COV2.S boosting. Homologous mRNA vaccine boosting generates nearly equivalent neutralizing activity against Omicron sublineages BA.1, BA.2, and BA.3 but modestly reduced neutralizing activity against BA.2.12.1 and BA.4/BA.5 compared with BA.1. These results have implications for boosting requirements to protect against Omicron and future variants of SARS-CoV-2. This trial was conducted under ClincalTrials.gov: NCT04889209.

KW - BA.2.12.1

KW - BA.4/BA.5

KW - COVID-19

KW - Omicron variant

KW - SARS-CoV-2

KW - booster

KW - mRNA vaccine

KW - neutralizing antibody

KW - recombinant adenovirus vaccine

KW - sublineage

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U2 - 10.1016/j.xcrm.2022.100679

DO - 10.1016/j.xcrm.2022.100679

M3 - Article

C2 - 35798000

AN - SCOPUS:85133791980

SN - 2666-3791

VL - 3

JO - Cell Reports Medicine

JF - Cell Reports Medicine

IS - 7

M1 - 100679

ER -

Rapid decline in vaccine-boosted neutralizing antibodies against SARS-CoV-2 Omicron variant

Abstract

Keywords

ASJC Scopus subject areas

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