Anti-neuraminidase and anti-hemagglutinin stalk responses to different influenza a(H7N9) vaccine regimens

Hana M. El Sahly; Evan J. Anderson; Lisa A. Jackson; Kathleen M. Neuzil; Robert L. Atmar; David I. Bernstein; Wilbur H. Chen; C. Buddy Creech; Sharon E. Frey; Paul Goepfert; Jeffery Meier; Varun Phadke; Nadine Rouphael; Richard Rupp; Jack T. Stapleton; Paul Spearman; Emmanuel B. Walter; Patricia L. Winokur; Inci Yildirim; Jennifer Oshinsky; Tracie L. Williams; Lynda Coughlan; Haye Nijhuis; Marcela F. Pasetti; Florian Krammer; Daniel Stadlbauer; Raffael Nachbagauer; Rachel Tsong; Ashley Wegel; Paul C. Roberts

doi:10.1016/j.vaccine.2024.126689

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Anti-neuraminidase and anti-hemagglutinin stalk responses to different influenza a(H7N9) vaccine regimens

Journal article

Peer reviewed

Anti-neuraminidase and anti-hemagglutinin stalk responses to different influenza a(H7N9) vaccine regimens

Hana M. El Sahly, Evan J. Anderson, Lisa A. Jackson, Kathleen M. Neuzil, Robert L. Atmar, David I. Bernstein, Wilbur H. Chen, C. Buddy Creech, Sharon E. Frey, Paul Goepfert, …

Vaccine, Vol.47, 126689

02/15/2025

DOI: 10.1016/j.vaccine.2024.126689

PMCID: PMC12697238

PMID: 39756216

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https://pmc.ncbi.nlm.nih.gov/articles/PMC12697238/pdf/nihms-2123204.pdfView

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Abstract

Pandemic influenza vaccine development focuses on the hemagglutinin (HA) antigen for potency and immunogenicity. Antibody responses targeting the neuraminidase (NA) antigen, or the HA stalk domain have been implicated in protection against influenza. Responses to the NA and HA-stalk domain following pandemic inactivated influenza are not well characterized in humans. In a series of clinical trials, we determine the vaccines' NA content and demonstrate that NA inhibition (NAI) antibody responses increase in a dose-dependent manner following a 2-dose priming series with AS03-adjuvanted influenza A(H7N9) inactivated vaccine (A(H7N9) IIV). NAI antibody responses also increase with interval extension of the 2-dose priming series or following a 5-year delayed boost with a heterologous adjuvanted A(H7N9) IIV. Neither concomitant seasonal influenza vaccination given simultaneously or sequentially, nor use of heterologous A(H7N9) IIVs in the 2-dose priming series had an appreciable effect on NAI antibody responses. Anti-HA stalk antibody responses were minimal and not durable. We provide evidence for strategies to improve anti-neuraminidase responses which can be further standardized for pandemic preparedness. NCT03312231, NCT03318315, NCT03589807, NCT03738241. •Neuraminidase and hemagglutinin's stalk antibodies are not well characterized post pandemic influenza vaccines.•Neuraminidase inhibition antibody responses increase in a dose dependent fashion after 2 doses of influenza A(H7N9) vaccine.•Increasing the interval of the 2-dose series and a delayed heterologous boost increased neuraminidase responses.•Concomitant seasonal influenza vaccination or use of heterologous A(H7N9) IIVs had no effect on neuraminidase responses.•Anti-hemagglutinin stalk responses were of small magnitude and transient.

Details

Title: Subtitle: Anti-neuraminidase and anti-hemagglutinin stalk responses to different influenza a(H7N9) vaccine regimens
Creators: Hana M. El Sahly - Baylor College of Medicine
Evan J. Anderson - Emory University
Lisa A. Jackson - Kaiser Permanente Washington Health Research Institute
Kathleen M. Neuzil - University of Maryland, Baltimore
Robert L. Atmar - Baylor College of Medicine
David I. Bernstein - University of Cincinnati
Wilbur H. Chen - University of Maryland, Baltimore
C. Buddy Creech - Vanderbilt University Medical Center
Sharon E. Frey - Saint Louis University
Paul Goepfert - University of Alabama at Birmingham
Jeffery Meier - University of Iowa
Varun Phadke - Emory University
Nadine Rouphael - Emory University
Richard Rupp - The University of Texas Medical Branch at Galveston
Jack T. Stapleton - University of Iowa
Paul Spearman - Cincinnati Children's Hospital Medical Center
Emmanuel B. Walter - Duke University
Patricia L. Winokur - University of Iowa
Inci Yildirim - Emory University School of Medicine
Jennifer Oshinsky - University of Maryland, Baltimore
Tracie L. Williams - National Center for Environmental Health
Lynda Coughlan - University of Maryland, Baltimore
Haye Nijhuis - University of Maryland, Baltimore
Marcela F. Pasetti - University of Maryland, Baltimore
Florian Krammer - Icahn School of Medicine at Mount Sinai
Daniel Stadlbauer - Icahn School of Medicine at Mount Sinai
Raffael Nachbagauer - Icahn School of Medicine at Mount Sinai
Rachel Tsong - Emmes (United States)
Ashley Wegel - Emmes (United States)
Paul C. Roberts - National Institutes of Health
Resource Type: Journal article
Publication Details: Vaccine, Vol.47, 126689
DOI: 10.1016/j.vaccine.2024.126689
PMID: 39756216
PMCID: PMC12697238
NLM abbreviation: Vaccine
ISSN: 0264-410X
eISSN: 1873-2518
Publisher: Elsevier Ltd
Grant note: National Institutes of Allergy and Infectious: HHSN272201300015I, 75N93021C00012, HHSN2722013000017I, HHSN272201300018I, HHSN272201300022I, HHSN272201300019I, HHSN272201300020I, HHSN272201300023I, HHSN27220130021I, HHSN272201300016I Department of Health and Human ServicesAdministration for Strategic Preparedness and ResponseBiomedical Advanced Research and Development Authority: HHSO100201600006I, HHSO1002012000131I, HHSO100201600004I National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services: HHSN272201800003I/75N93020F00001 NIAID: HHSN272201300022I, 75N93019C00055 NIAID Centers of Excellence for Influenza Research and Response (CEIRR): 75N93021C00014
The work was supported by the National Institutes of Allergy and Infectious contract HHSN272201300015I (Baylor College of Medicine), 75N93021C00012 (The Emmes Company, LLC), HHSN2722013000017I (Duke University School of Medicine), HHSN272201300018I (Emory University), HHSN272201300022I (University of Maryland), HHSN272201300019I (Kaiser Washington), HHSN272201300020I (University of Iowa), HHSN272201300023I (Vanderbilt University Medical Center), HHSN27220130021I (Saint Louis University) HHSN272201300016I (Cincinnati Children's Hospital Medical Center).The candidate vaccines evaluated under this study have been funded in whole or in part with Federal funds from the Department of Health and Human Services; Administration for Strategic Preparedness and Response; Biomedical Advanced Research and Development Authority, under Contracts HHSO100201600006I, HHSO1002012000131I, HHSO100201600004I. The contracts and federal funding are not an endorsement of the study results, product, or company. The vaccine antigen was manufactured by Sanofi (H7N9 vaccine). AS03 is a trademark owned by or licensed to the GSK group of companies. Both manufacturers were provided the opportunity to review a preliminary version of this manuscript for factual accuracy, but the authors are solely responsible for final content and interpretation. The NAI assessments were funded with Federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under Preclinical Services Contract No. HHSN272201800003I/75N93020F00001. HA stalk antigens were designed and produced with support from R01AI148369 (LC) and NIAID contract and 75N93019C00055. The HA stalk antibody assessments were funded by NIAID contract HHSN272201300022I. Work in the Krammer laboratory was supported via the NIAID Centers of Excellence for Influenza Research and Response (CEIRR, 75N93021C00014).
Language: English
Electronic publication date: 01/04/2025
Date published: 02/15/2025
Academic Unit: Microbiology and Immunology; Infectious Diseases; Epidemiology; Medicine Administration; Internal Medicine
Record Identifier: 9984771633802771

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