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
{"title":"抗神经氨酸酶和抗血凝素柄对不同甲型H7N9流感疫苗方案的反应","authors":"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","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>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.</p><p><strong>Material and methods: </strong>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.</p><p><strong>Conclusions: </strong>We provide evidence for strategies to improve anti-neuraminidase responses which can be further standardized for pandemic preparedness.</p><p><strong>Clinical trial registry numbers: </strong>NCT03312231, NCT03318315, NCT03589807, NCT03738241.</p>","PeriodicalId":94264,"journal":{"name":"Vaccine","volume":"47 ","pages":"126689"},"PeriodicalIF":0.0000,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Anti-neuraminidase and anti-hemagglutinin stalk responses to different influenza a(H7N9) vaccine regimens.\",\"authors\":\"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\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>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.</p><p><strong>Material and methods: </strong>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.</p><p><strong>Conclusions: </strong>We provide evidence for strategies to improve anti-neuraminidase responses which can be further standardized for pandemic preparedness.</p><p><strong>Clinical trial registry numbers: </strong>NCT03312231, NCT03318315, NCT03589807, NCT03738241.</p>\",\"PeriodicalId\":94264,\"journal\":{\"name\":\"Vaccine\",\"volume\":\"47 \",\"pages\":\"126689\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2025-02-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Vaccine\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1016/j.vaccine.2024.126689\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/1/4 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Vaccine","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1016/j.vaccine.2024.126689","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/4 0:00:00","PubModel":"Epub","JCR":"","JCRName":"","Score":null,"Total":0}
Anti-neuraminidase and anti-hemagglutinin stalk responses to different influenza a(H7N9) vaccine regimens.
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.
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