Your browser doesn't support javascript.
An influenza hemagglutinin stem nanoparticle vaccine induces cross-group 1 neutralizing antibodies in healthy adults.
Widge, Alicia T; Hofstetter, Amelia R; Houser, Katherine V; Awan, Seemal F; Chen, Grace L; Burgos Florez, Maria C; Berkowitz, Nina M; Mendoza, Floreliz; Hendel, Cynthia S; Holman, LaSonji A; Gordon, Ingelise J; Apte, Preeti; Liang, C Jason; Gaudinski, Martin R; Coates, Emily E; Strom, Larisa; Wycuff, Diane; Vazquez, Sandra; Stein, Judy A; Gall, Jason G; Adams, William C; Carlton, Kevin; Gillespie, Rebecca A; Creanga, Adrian; Crank, Michelle C; Andrews, Sarah F; Castro, Mike; Serebryannyy, Leonid A; Narpala, Sandeep R; Hatcher, Christian; Lin, Bob C; O'Connell, Sarah; Freyn, Alec W; Rosado, Victoria C; Nachbagauer, Raffael; Palese, Peter; Kanekiyo, Masaru; McDermott, Adrian B; Koup, Richard A; Dropulic, Lesia K; Graham, Barney S; Mascola, John R; Ledgerwood, Julie E.
  • Widge AT; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Hofstetter AR; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Houser KV; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Awan SF; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Chen GL; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Burgos Florez MC; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Berkowitz NM; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Mendoza F; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Hendel CS; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Holman LA; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Gordon IJ; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Apte P; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Liang CJ; Biostatistics Research Branch, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Gaudinski MR; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Coates EE; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Strom L; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Wycuff D; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Vazquez S; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Stein JA; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Gall JG; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Adams WC; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Carlton K; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Gillespie RA; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Creanga A; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Crank MC; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Andrews SF; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Castro M; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Serebryannyy LA; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Narpala SR; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Hatcher C; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Lin BC; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • O'Connell S; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Freyn AW; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Rosado VC; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Nachbagauer R; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Palese P; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Kanekiyo M; Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • McDermott AB; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Koup RA; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Dropulic LK; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Graham BS; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Mascola JR; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Ledgerwood JE; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Sci Transl Med ; 15(692): eade4790, 2023 04 19.
Article in English | MEDLINE | ID: covidwho-2305673
ABSTRACT
Influenza vaccines could be improved by platforms inducing cross-reactive immunity. Immunodominance of the influenza hemagglutinin (HA) head in currently licensed vaccines impedes induction of cross-reactive neutralizing stem-directed antibodies. A vaccine without the variable HA head domain has the potential to focus the immune response on the conserved HA stem. This first-in-human dose-escalation open-label phase 1 clinical trial (NCT03814720) tested an HA stabilized stem ferritin nanoparticle vaccine (H1ssF) based on the H1 HA stem of A/New Caledonia/20/1999. Fifty-two healthy adults aged 18 to 70 years old enrolled to receive either 20 µg of H1ssF once (n = 5) or 60 µg of H1ssF twice (n = 47) with a prime-boost interval of 16 weeks. Thirty-five (74%) 60-µg dose participants received the boost, whereas 11 (23%) boost vaccinations were missed because of public health restrictions in the early stages of the COVID-19 pandemic. The primary objective of this trial was to evaluate the safety and tolerability of H1ssF, and the secondary objective was to evaluate antibody responses after vaccination. H1ssF was safe and well tolerated, with mild solicited local and systemic reactogenicity. The most common symptoms included pain or tenderness at the injection site (n = 10, 19%), headache (n = 10, 19%), and malaise (n = 6, 12%). We found that H1ssF elicited cross-reactive neutralizing antibodies against the conserved HA stem of group 1 influenza viruses, despite previous H1 subtype head-specific immunity. These responses were durable, with neutralizing antibodies observed more than 1 year after vaccination. Our results support this platform as a step forward in the development of a universal influenza vaccine.
Subject(s)
Fulltext
Print
XML
PubMed Links
Search on Google

Full text: Available Collection: International databases Database: MEDLINE Main subject: Influenza Vaccines / Influenza, Human / COVID-19 Type of study: Experimental Studies / Prognostic study / Randomized controlled trials Topics: Vaccines Limits: Adolescent / Adult / Aged / Humans / Middle aged / Young adult Language: English Journal: Sci Transl Med Journal subject: Science / Medicine Year: 2023 Document Type: Article Affiliation country: Scitranslmed.ade4790

Similar

MEDLINE
LILACS
LIS
Fulltext
Print
XML
PubMed Links
Search on Google

Full text: Available Collection: International databases Database: MEDLINE Main subject: Influenza Vaccines / Influenza, Human / COVID-19 Type of study: Experimental Studies / Prognostic study / Randomized controlled trials Topics: Vaccines Limits: Adolescent / Adult / Aged / Humans / Middle aged / Young adult Language: English Journal: Sci Transl Med Journal subject: Science / Medicine Year: 2023 Document Type: Article Affiliation country: Scitranslmed.ade4790