Safety and immunogenicity of a ferritin nanoparticle H2 influenza vaccine in healthy adults: a phase 1 trial.
Клиническое исследование I фазыСтатьяРандомизированное исследованиеПоддержка NIH: внешняя программаResearch Support, N.I.H., IntramuralНазвание и аннотация: Перевод в очереди
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Houser Katherine V, Chen Grace L, Carter Cristina, Crank Michelle C, Nguyen Thuy A, Burgos Florez Maria Claudia, Berkowitz Nina M, Mendoza Floreliz, Hendel Cynthia Starr, Gordon Ingelise J, Coates Emily E, Vazquez Sandra, Stein Judy, Case Christopher L, Lawlor Heather, Carlton Kevin, Gaudinski Martin R, Strom Larisa, Hofstetter Amelia R, Liang C Jason, Narpala Sandeep, Hatcher Christian, Gillespie Rebecca A, Creanga Adrian, Kanekiyo Masaru, Raab Julie E, Andrews Sarah F, Zhang Yi, Yang Eun Sung, Wang Lingshu, Leung Kwanyee, Kong Wing-Pui, Freyn Alec W, Nachbagauer Raffael, Palese Peter, Bailer Robert T, McDermott Adrian B, Koup Richard A, Gall Jason G, Arnold Frank, Mascola John R, Graham Barney S, Ledgerwood Julie E, VRC 316 Study Team
Аннотация
Currently, licensed seasonal influenza vaccines display variable vaccine effectiveness, and there remains a need for novel vaccine platforms capable of inducing broader responses against viral protein domains conserved among influenza subtypes. We conducted a first-in-human, randomized, open-label, phase 1 clinical trial ( NCT03186781 ) to evaluate a novel ferritin (H2HA-Ferritin) nanoparticle influenza vaccine platform. The H2 subtype has not circulated in humans since 1968. Adults born after 1968 have been exposed to only the H1 subtype of group 1 influenza viruses, which shares a conserved stem with H2. Including both H2-naive and H2-exposed adults in the trial allowed us to evaluate memory responses against the conserved stem domain in the presence or absence of pre-existing responses against the immunodominant HA head domain. Fifty healthy participants 18-70 years of age received H2HA-Ferritin intramuscularly as a single 20-μg dose (n = 5) or a 60-μg dose either twice in a homologous (n = 25) prime-boost regimen or once in a heterologous (n = 20) prime-boost regimen after a matched H2 DNA vaccine prime. The primary objective of this trial was to evaluate the safety and tolerability of H2HA-Ferritin either alone or in prime-boost regimens. The secondary objective was to evaluate antibody responses after vaccination. Both vaccines were safe and well tolerated, with the most common solicited symptom being mild headache after both H2HA-Ferritin (n = 15, 22%) and H2 DNA (n = 5, 25%). Exploratory analyses identified neutralizing antibody responses elicited by the H2HA-Ferritin vaccine in both H2-naive and H2-exposed populations. Furthermore, broadly neutralizing antibody responses against group 1 influenza viruses, including both seasonal H1 and avian H5 subtypes, were induced in the H2-naive population through targeting the HA stem. This ferritin nanoparticle vaccine technology represents a novel, safe and immunogenic platform with potential application for pandemic preparedness and universal influenza vaccine development.