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Clinical Trial
. 2025 Feb 15:47:126689.
doi: 10.1016/j.vaccine.2024.126689. Epub 2025 Jan 4.

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

Hana M El Sahly  1 , Evan J Anderson  2 , Lisa A Jackson  3 , Kathleen M Neuzil  4 , Robert L Atmar  5 , David I Bernstein  6 , Wilbur H Chen  4 , C Buddy Creech  7 , Sharon E Frey  8 , Paul Goepfert  9 , Jeffery Meier  10 , Varun Phadke  11 , Nadine Rouphael  11 , Richard Rupp  12 , Jack T Stapleton  10 , Paul Spearman  6 , Emmanuel B Walter  13 , Patricia L Winokur  10 , Inci Yildirim  2 , Tracie L Williams  14 , Jennifer Oshinsky  4 , Lynda Coughlan  4 , Haye Nijhuis  4 , Marcela F Pasetti  4 , Florian Krammer  15 , Daniel Stadlbauer  15 , Raffael Nachbagauer  15 , Rachel Tsong  16 , Ashley Wegel  16 , Paul C Roberts  17
Affiliations
Clinical Trial

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

Hana M El Sahly et al. Vaccine. .

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.

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Conflict of interest statement

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Figure 1.
Figure 1.
Geometric Mean Titers of Neuraminidase Inhibition Antibody Against A/Hong Kong/125/2017 (H7N9) by Study Day, Study Group, and Age Stratum, DMID 17–0075 Exploratory Immunogenicity Population. Day 1 N=702, Day 22 N=672, Day 43 N=640
Figure 2.
Figure 2.
Geometric Mean Titers of Neuraminidase Inhibition Antibody by Strain, Study Day, and Study Group, DMID 17–0077 Exploratory Immunogenicity Population. Day 1 N=138, Day 22 N=136, Day 181 N=125
Figure 3.
Figure 3.
Geometric Mean Titers of Neuraminidase Inhibition Antibody Against A/Hong Kong/125/2017 (H7N9) by Study Day and Study Group, DMID 17–0078 Exploratory Immunogenicity Population. Day 1 N=132, Day 22 N=128, Day 43 N=48 (only Groups 1, 4), Day 121 N=97 (only Groups 2, 3, 5, 6), Day 142 N=94, Day 202 N=50(only Groups 1, 4), Day 301 N=84 (only Groups 2, 3, 5, 6),
Figure 4.
Figure 4.
Geometric Mean Titers of Neuraminidase Inhibition Antibody Against A/Hong Kong/125/2017 (H7N9) by Study Day and Study Group, DMID 17–0090 Exploratory Immunogenicity Population. Day 1 N=301, Day 8 N=301, Day 22 N=300, Day 181 N=298
Figure 5.
Figure 5.
Geometric Mean Concentration of Anti-Hemagglutinin-Stalk Antibody by Study Day and Study Group, DMID 17–0078 (Panel A) and DMID 17–0090 (Panel B) Exploratory Immunogenicity Populations. DMID 17–0078: Day 1 N=132, Day 22 N=128, Day 43 N=48 (only Groups 1, 4), Day 121 N=97 (only Groups 2, 3, 5, 6), Day 142 N=94, Day 202 N=50(only Groups 1, 4), Day 301 N=84 (only Groups 2, 3, 5, 6). DMID 17–0090 Day 1 N=299, Day 8 N=300, Day 22 N=299, Day 181 N=297.
Figure 5.
Figure 5.
Geometric Mean Concentration of Anti-Hemagglutinin-Stalk Antibody by Study Day and Study Group, DMID 17–0078 (Panel A) and DMID 17–0090 (Panel B) Exploratory Immunogenicity Populations. DMID 17–0078: Day 1 N=132, Day 22 N=128, Day 43 N=48 (only Groups 1, 4), Day 121 N=97 (only Groups 2, 3, 5, 6), Day 142 N=94, Day 202 N=50(only Groups 1, 4), Day 301 N=84 (only Groups 2, 3, 5, 6). DMID 17–0090 Day 1 N=299, Day 8 N=300, Day 22 N=299, Day 181 N=297.
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