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; Tracie L. Williams; Jennifer Oshinsky; 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

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, Tracie L. WilliamsJennifer Oshinsky, Lynda Coughlan, Haye Nijhuis, Marcela F. Pasetti, Florian Krammer, Daniel Stadlbauer, Raffael Nachbagauer, Rachel Tsong, Ashley Wegel, Paul C. Roberts

Pediatrics

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

Abstract

Introduction: 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. Material and methods: 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. Conclusions: We provide evidence for strategies to improve anti-neuraminidase responses which can be further standardized for pandemic preparedness. Clinical Trial Registry Numbers: NCT03312231, NCT03318315, NCT03589807, NCT03738241.

Original language	English (US)
Article number	126689
Journal	Vaccine
Volume	47
DOIs	https://doi.org/10.1016/j.vaccine.2024.126689
State	Published - Feb 15 2025

ASJC Scopus subject areas

Molecular Medicine
General Immunology and Microbiology
General Veterinary
Public Health, Environmental and Occupational Health
Infectious Diseases

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10.1016/j.vaccine.2024.126689

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El Sahly, H. M., Anderson, E. J., Jackson, L. A., Neuzil, K. M., Atmar, R. L., Bernstein, D. I., Chen, W. H., Creech, C. B., Frey, S. E., Goepfert, P., Meier, J., Phadke, V., Rouphael, N., Rupp, R., Stapleton, J. T., Spearman, P., Walter, E. B., Winokur, P. L., Yildirim, I., ... Roberts, P. C. (2025). Anti-neuraminidase and anti-hemagglutinin stalk responses to different influenza a(H7N9) vaccine regimens. Vaccine, 47, Article 126689. https://doi.org/10.1016/j.vaccine.2024.126689

El Sahly, HM, Anderson, EJ, Jackson, LA, Neuzil, KM, Atmar, RL, Bernstein, DI, Chen, WH, Creech, CB, Frey, SE, Goepfert, P, Meier, J, Phadke, V, Rouphael, N, Rupp, R, Stapleton, JT, Spearman, P, Walter, EB, Winokur, PL, Yildirim, I, Williams, TL, Oshinsky, J, Coughlan, L, Nijhuis, H, Pasetti, MF, Krammer, F, Stadlbauer, D, Nachbagauer, R, Tsong, R, Wegel, A & Roberts, PC 2025, 'Anti-neuraminidase and anti-hemagglutinin stalk responses to different influenza a(H7N9) vaccine regimens', Vaccine, vol. 47, 126689. https://doi.org/10.1016/j.vaccine.2024.126689

@article{2bab29d52edc4b36933705fc51373a6c,

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

abstract = "Introduction: 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. Material and methods: 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. Conclusions: We provide evidence for strategies to improve anti-neuraminidase responses which can be further standardized for pandemic preparedness. Clinical Trial Registry Numbers: NCT03312231, NCT03318315, NCT03589807, NCT03738241.",

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

note = "Publisher Copyright: {\textcopyright} 2025 Elsevier Ltd",

year = "2025",

month = feb,

day = "15",

doi = "10.1016/j.vaccine.2024.126689",

language = "English (US)",

volume = "47",

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TY - JOUR

T1 - Anti-neuraminidase and anti-hemagglutinin stalk responses to different influenza a(H7N9) vaccine regimens

AU - El Sahly, Hana M.

AU - Anderson, Evan J.

AU - Jackson, Lisa A.

AU - Neuzil, Kathleen M.

AU - Atmar, Robert L.

AU - Bernstein, David I.

AU - Chen, Wilbur H.

AU - Creech, C. Buddy

AU - Frey, Sharon E.

AU - Goepfert, Paul

AU - Meier, Jeffery

AU - Phadke, Varun

AU - Rouphael, Nadine

AU - Rupp, Richard

AU - Stapleton, Jack T.

AU - Spearman, Paul

AU - Walter, Emmanuel B.

AU - Winokur, Patricia L.

AU - Yildirim, Inci

AU - Williams, Tracie L.

AU - Oshinsky, Jennifer

AU - Coughlan, Lynda

AU - Nijhuis, Haye

AU - Pasetti, Marcela F.

AU - Krammer, Florian

AU - Stadlbauer, Daniel

AU - Nachbagauer, Raffael

AU - Tsong, Rachel

AU - Wegel, Ashley

AU - Roberts, Paul C.

PY - 2025/2/15

Y1 - 2025/2/15

N2 - Introduction: 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. Material and methods: 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. Conclusions: We provide evidence for strategies to improve anti-neuraminidase responses which can be further standardized for pandemic preparedness. Clinical Trial Registry Numbers: NCT03312231, NCT03318315, NCT03589807, NCT03738241.

AB - Introduction: 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. Material and methods: 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. Conclusions: We provide evidence for strategies to improve anti-neuraminidase responses which can be further standardized for pandemic preparedness. Clinical Trial Registry Numbers: NCT03312231, NCT03318315, NCT03589807, NCT03738241.

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U2 - 10.1016/j.vaccine.2024.126689

DO - 10.1016/j.vaccine.2024.126689

M3 - Article

C2 - 39756216

AN - SCOPUS:85213866041

SN - 0264-410X

VL - 47

JO - Vaccine

JF - Vaccine

M1 - 126689

ER -

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

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