TY - JOUR
T1 - An influenza hemagglutinin stem nanoparticle vaccine induces cross-group 1 neutralizing antibodies in healthy adults
AU - VRC 321 study team
AU - Widge, Alicia T.
AU - Hofstetter, Amelia R.
AU - Houser, Katherine V.
AU - Awan, Seemal F.
AU - Chen, Grace L.
AU - Florez, Maria C.Burgos
AU - Berkowitz, Nina M.
AU - Mendoza, Floreliz
AU - Hendel, Cynthia S.
AU - LaSonji, A. Holman
AU - Gordon, Ingelise J.
AU - Apte, Preeti
AU - Liang, C. Jason
AU - Gaudinski, Martin R.
AU - Coates, Emily E.
AU - Strom, Larisa
AU - Wycuff, Diane
AU - Vazquez, Sandra
AU - Stein, Judy A.
AU - Gall, Jason G.
AU - Adams, William C.
AU - Carlton, Kevin
AU - Gillespie, Rebecca A.
AU - Creanga, Adrian
AU - Crank, Michelle C.
AU - Andrews, Sarah F.
AU - Castro, Mike
AU - Serebryannyy, Leonid A.
AU - Narpala, Sandeep R.
AU - Hatcher, Christian
AU - Lin, Bob C.
AU - O'Connell, Sarah
AU - Freyn, Alec W.
AU - Rosado, Victoria C.
AU - Nachbagauer, Raffael
AU - Palese, Peter
AU - Kanekiyo, Masaru
AU - McDermott, Adrian B.
AU - Koup, Richard A.
AU - Dropulic, Lesia K.
AU - Graham, Barney S.
AU - Mascola, John R.
AU - Ledgerwood, Julie E.
AU - Beck, Allison
AU - Casazza, Joseph
AU - Case, Christopher L.
AU - Misasi, John
AU - Ola, Abidemi O.
AU - Parker, Karen
AU - Wu, Richard
N1 - Publisher Copyright:
Copyright © 2023 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S.
PY - 2023/4/19
Y1 - 2023/4/19
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85152979501&partnerID=8YFLogxK
U2 - 10.1126/scitranslmed.ade4790
DO - 10.1126/scitranslmed.ade4790
M3 - Article
C2 - 37075129
AN - SCOPUS:85152979501
SN - 1946-6234
VL - 15
JO - Science Translational Medicine
JF - Science Translational Medicine
IS - 692
M1 - eade4790
ER -