puc-header

Rapid Decline in Vaccine-Boosted Neutralizing Antibodies Against SARS-CoV-2 Omicron Variant

57 Pages Posted: 8 Apr 2022 Publication Status: Accepted

See all articles by Kirsten E. Lyke

Kirsten E. Lyke

University of Maryland School of Medicine - Center for Vaccine Development and Global Health

Robert L. Atmar

Baylor College of Medicine

Clara Dominguez Islas

affiliation not provided to SSRN

Christine M. Posavad

affiliation not provided to SSRN

Daniel Szydlo

affiliation not provided to SSRN

Rahul PaulChourdhury

affiliation not provided to SSRN

Meagan E. Deming

University of Maryland School of Medicine

Amanda Eaton

Duke University School of Medicine - Duke Human Vaccine Institute

Lisa A. Jackson

Kaiser Permanente Washington Health Research Institute

Angela Ramon Branche

University of Rochester - Division of Infectious Diseases

Hana M. El Sahly

Baylor College of Medicine

Christina Rostad

Emory University - Department of Pediatrics

Judith M. Martin

University of Pittsburgh - School of Medicine

Christine Johnston

University of Washington

Richard Rupp

University of Texas Medical Branch-Galveston - The Sealy Institute for Vaccine Sciences

Mark J. Mulligan

New York University Grossman School of Medicine

Rebecca C. Brady

affiliation not provided to SSRN

Robert Frenck

Cincinnati Children's Hospital Medical Center - Division of Infectious Diseases

Martin Bäcker

affiliation not provided to SSRN

Angelica Kottkamp

New York University Grossman School of Medicine

Tara M. Babu

affiliation not provided to SSRN

Kumaravel Rajakumar

University of Pittsburgh - School of Medicine

Srilatha Edupuganti

Emory University - School of Medicine

David Dobrzynski

affiliation not provided to SSRN

Rhea N. Coler

affiliation not provided to SSRN

Janet I. Archer

affiliation not provided to SSRN

Sonja Crandon

Government of the United States of America - National Institute of Allergy and Infectious Diseases (NIAID)

Jillian A. Zemanek

affiliation not provided to SSRN

Elizabeth R. Brown

University of Washington - Vaccine and Infectious Disease Division

Kathleen M. Neuzil

University of Maryland - Center for Vaccine Development and Global Health

David S. Stephens

affiliation not provided to SSRN

Diane J. Post

Government of the United States of America - National Institute of Allergy and Infectious Diseases (NIAID)

Seema U. Nayak

Government of the United States of America - National Institute of Allergy and Infectious Diseases (NIAID)

Mehul Suthar

Emory University - Center for Childhood Infections and Vaccines

Paul C. Roberts

Government of the United States of America - National Institute of Allergy and Infectious Diseases (NIAID)

John H. Beigel

Government of the United States of America - National Institute of Allergy and Infectious Diseases (NIAID)

David C. Montefiori

Duke University

DMID 21-0012 Study Group

More...

Abstract

The Omicron variant of SARS-CoV-2 exhibits reduced susceptibility to vaccine-induced neutralizing antibodies, requiring a boost to generate protective immunity. Little is known about the durability of vaccine-boosted omicron neutralizing antibodies and the potential impact of boosting with heterologous vaccine modalities. We assessed the magnitude and short-term durability of neutralizing antibodies after homologous and heterologous boosting with mRNA and Ad26.COV2.S vaccines. Using pseudovirus and live virus neutralization assays, all prime-boost combinations substantially increased the neutralization titers to Omicron although the boosted titers declined rapidly within 2 months from the peak response compared to boosted titers against the prototypic D614G variant. Boosted Omicron neutralization titers were substantially higher for homologous mRNA vaccine boosting, and for heterologous mRNA and Ad26.COV2.S vaccine boosting, compared to homologous Ad26.COV2.S boosting. Homologous mRNA vaccine boosting generated nearly equivalent neutralizing activity against Omicron subvariants BA.1, BA.2 and BA.3. These results have implications for boosting requirements to protect against Omicron and future variants of SARS-CoV-2.

Trial Registration: Clinical Trials.gov number, NCT04889209.

Funding Information: The trial was sponsored and primarily funded by the Infectious Diseases Clinical Research Consortium through the National Institute for Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH), under award numbers UM1AI48372, UM1AI148373, UM1AI148450, UM1AI148452, UM1AI148573, UM1AI148574, UM1AI148575, UM1AI148576, UM1AI148684, 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: NIH P51 OD011132, 3U19AI057266-17S1, 1U54CA260563, HHSN272201400004C, NIH/NIAID CEIRR under contract 75N93021C00017 to Emory University) from NIAID and Emory School of Medicine, Woodruff Health Sciences Center 2020 COVID-19 CURE Award.

Conflict of Interests: RLA, CPDI, CMP, DS, RP, MED, AE, HME, RER, MB, ACK, TMB, DD, RNC, JLA, SC, JAZ, SUN, ERB, DJP, and SUN report no competing interests. KEL receives grant awards from Pfizer Inc. COVID-19 vaccine research. LAJ’s institution receives grant funding from NIH and CDC for vaccine-related assessments, including those of COVID-19 vaccines. ARB has grant funding from Pfizer, Janssen, Merck and Cyanvac for non-COVID-19-related work and serves as a consultant for GSK and Janssen. CAR'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, Sanofi-Pasteur. She is co-inventor of patented RSV vaccine technology, which has been licensed to Meissa Vaccines, Inc. JMM has served as a consultant for Merck, Sharp and Dohme for non-Covid- 14 related work. CJ 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. MJM has laboratory research and clinical trials contracts for vaccines or MAB vs SARS-CoV-2 with Lilly, Pfizer (exclusive of the current work), and Sanofi; personal fees for Scientific Advisory Board service from Merck, Meissa Vaccines, Inc. and Pfizer. RCB receives funding for vaccine trials from Path Nipah and Pfizer. RWF 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. SE receives funding to her institution from Sanofi Pasteur for a non-COVID-19 vaccine study. KMN 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. DSS is supported by grant awards from NIH/NIAID. PCR and JHB report a pending U.S. Patent Application No. 63/025,918 entitled “Coronavirus RNA vaccines and methods of use” DCM receives funding from NIH and Moderna for laboratory studies of COVID-19 vaccine antibody responses. MSS receives funding from Moderna Inc. and Ocugen. DM receives funding from Moderna Inc.

Ethical Approval: Ethics Approval Statement: Ethical approval for the study was given by the Advarra IRB (www.advarra.com) of Columbia, MD (OHRP FWA: 00023875) with additional site-specific approvals provided.

Keywords: COVID-19, SARS-CoV-2, Booster, Vaccine, Omicron variant, B.1.1.529, Neutralizing antibody, mRNA vaccine, recombinant adenovirus vaccine

Suggested Citation

Lyke, Kirsten E. and Atmar, Robert L. and Dominguez Islas, Clara and Posavad, Christine M. and Szydlo, Daniel and PaulChourdhury, Rahul and Deming, Meagan E. and Eaton, Amanda and Jackson, Lisa A. and Branche, Angela Ramon and El Sahly, Hana M. and Rostad, Christina and Martin, Judith M. and Johnston, Christine and Rupp, Richard and Mulligan, Mark J. and Brady, Rebecca C. and Frenck, Robert and Bäcker, Martin and Kottkamp, Angelica and Babu, Tara M. and Rajakumar, Kumaravel and Edupuganti, Srilatha and Dobrzynski, David and Coler, Rhea N. and Archer, Janet I. and Crandon, Sonja 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 and Roberts, Paul C. and Beigel, John H. and Montefiori, David C. and Group, DMID 21-0012 Study, Rapid Decline in Vaccine-Boosted Neutralizing Antibodies Against SARS-CoV-2 Omicron Variant. Available at SSRN: https://ssrn.com/abstract=4061187 or http://dx.doi.org/10.2139/ssrn.4061187
This version of the paper has not been formally peer reviewed.

Kirsten E. Lyke (Contact Author)

University of Maryland School of Medicine - Center for Vaccine Development and Global Health ( email )

United States

Robert L. Atmar

Baylor College of Medicine ( email )

United States

Clara Dominguez Islas

affiliation not provided to SSRN ( email )

No Address Available

Christine M. Posavad

affiliation not provided to SSRN ( email )

No Address Available

Daniel Szydlo

affiliation not provided to SSRN ( email )

No Address Available

Rahul PaulChourdhury

affiliation not provided to SSRN ( email )

No Address Available

Meagan E. Deming

University of Maryland School of Medicine ( email )

670 West Baltimore Street
Baltimore, MD 21201
United States

Amanda Eaton

Duke University School of Medicine - Duke Human Vaccine Institute ( email )

Durham, NC 27710
United States

Lisa A. Jackson

Kaiser Permanente Washington Health Research Institute ( email )

1730 Minor Ave
Seattle, WA 98195
United States

Angela Ramon Branche

University of Rochester - Division of Infectious Diseases ( email )

Rochester, NY
United States

Hana M. El Sahly

Baylor College of Medicine ( email )

One Baylor Plaza
Apt 510
Houston, TX TX - Texas 77030
United States

Christina Rostad

Emory University - Department of Pediatrics ( email )

Atlanta, GA
United States

Judith M. Martin

University of Pittsburgh - School of Medicine ( email )

Pittsburgh, PA
United States

Christine Johnston

University of Washington

Seattle, WA 98195
United States

Richard Rupp

University of Texas Medical Branch-Galveston - The Sealy Institute for Vaccine Sciences ( email )

TX
United States

Mark J. Mulligan

New York University Grossman School of Medicine ( email )

Rebecca C. Brady

affiliation not provided to SSRN ( email )

No Address Available

Robert Frenck

Cincinnati Children's Hospital Medical Center - Division of Infectious Diseases ( email )

3333 Burnet Avenue
Cincinnati, OH 45229
United States

Martin Bäcker

affiliation not provided to SSRN ( email )

No Address Available

Angelica Kottkamp

New York University Grossman School of Medicine ( email )

Tara M. Babu

affiliation not provided to SSRN ( email )

No Address Available

Kumaravel Rajakumar

University of Pittsburgh - School of Medicine ( email )

Pittsburgh, PA
United States

Srilatha Edupuganti

Emory University - School of Medicine

1364 Clifton Rd. NE
Atlanta, GA 30322
United States

David Dobrzynski

affiliation not provided to SSRN ( email )

No Address Available

Rhea N. Coler

affiliation not provided to SSRN ( email )

No Address Available

Janet I. Archer

affiliation not provided to SSRN ( email )

No Address Available

Sonja Crandon

Government of the United States of America - National Institute of Allergy and Infectious Diseases (NIAID) ( email )

Bethesda, MD 20814
United States

Jillian A. Zemanek

affiliation not provided to SSRN ( email )

No Address Available

Elizabeth R. Brown

University of Washington - Vaccine and Infectious Disease Division ( email )

Kathleen M. Neuzil

University of Maryland - Center for Vaccine Development and Global Health ( email )

685 W. Baltimore St
Room 480
Baltimore, MD 21201
United States

David S. Stephens

affiliation not provided to SSRN ( email )

No Address Available

Diane J. Post

Government of the United States of America - National Institute of Allergy and Infectious Diseases (NIAID) ( email )

Bethesda, MD 20814
United States

Seema U. Nayak

Government of the United States of America - National Institute of Allergy and Infectious Diseases (NIAID) ( email )

Bethesda, MD 20814
United States

Mehul Suthar

Emory University - Center for Childhood Infections and Vaccines ( email )

United States

Paul C. Roberts

Government of the United States of America - National Institute of Allergy and Infectious Diseases (NIAID) ( email )

Bethesda, MD 20814
United States

John H. Beigel

Government of the United States of America - National Institute of Allergy and Infectious Diseases (NIAID) ( email )

Bethesda, MD 20814
United States

David C. Montefiori

Duke University ( email )

Department of Biostatistics and Bioinformatics
Durham, NC 27705
United States

No contact information is available for DMID 21-0012 Study Group

Click here to go to Cell.com

Paper statistics

Abstract Views
559
Downloads
56
PlumX Metrics