Safety and immunogenicity of a ferritin nanoparticle H2 influenza vaccine in healthy adults: a phase 1 trial.
Safety and immunogenicity of a ferritin nanoparticle H2 influenza vaccine in healthy adults: a phase 1 trial.
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DOI：
10.1038/s41591-021-01660-8
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发表时间：
2022-02
期刊：
影响因子：
82.9
通讯作者：
Ledgerwood, Julie E.
中科院分区：
文献类型：
--
作者：
Houser, Katherine, V;Chen, Grace L.;Carter, Cristina;Crank, Michelle C.;Nguyen, Thuy A.;Florez, Maria Claudia Burgos;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.
目前，许可的季节性流感疫苗显示出可变的疫苗有效性，并且仍然需要能够诱导针对流感亚型中保守的病毒蛋白结构域的更广泛应答的新型疫苗平台。我们进行了一项首次人体随机开放标签1期临床试验（NCT 03186781），以评估新型铁蛋白（H2 HA-铁蛋白）纳米颗粒流感疫苗平台。H2亚型自1968年以来就没有在人类中传播过。1968年以后出生的成年人只接触过第1组流感病毒的H1亚型，它与H2有一个保守的茎。在试验中包括H2-幼稚和H2-暴露的成人两者允许我们在存在或不存在针对免疫显性HA头部结构域的预先存在的应答的情况下评估针对保守的茎结构域的记忆应答。50名18-70岁的健康受试者在匹配的H2 DNA疫苗初免后，以20 μg单次剂量（n = 5）或60 μg单次剂量（n = 25）肌肉注射H2 HA-铁蛋白，在同源初免-加强方案中注射两次或在异源初免-加强方案中注射一次（n = 20）。本试验的主要目的是评估H2 HA-铁蛋白单独或在初免-加强方案中的安全性和耐受性。次要目的是评价疫苗接种后的抗体应答。两种疫苗均安全且耐受性良好，H2 HA-铁蛋白（n = 15，22%）和H2 DNA（n = 5，25%）接种后最常见的征集性症状为轻度头痛。探索性分析确定了H2 HA-铁蛋白疫苗在H2未接触和H2暴露人群中引起的中和抗体应答。此外，通过靶向HA茎，在H2初治人群中诱导了针对组1流感病毒（包括季节性H1和禽H5亚型）的广泛中和抗体应答。这种铁蛋白纳米颗粒疫苗技术代表了一种新的、安全的和免疫原性的平台，具有用于大流行防备和通用流感疫苗开发的潜在应用。
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.
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影响因子：
5.4
作者：
Hehme, N;Engelmann, H;Sänger, R
通讯作者：
Sänger, R
影响因子：
82.9
作者：
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影响因子：
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作者：
Talaat KR;Karron RA;Liang PH;McMahon BA;Luke CJ;Thumar B;Chen GL;Min JY;Lamirande EW;Jin H;Coelingh KL;Kemble GW;Subbarao K
通讯作者：
Subbarao K
影响因子：
9.2
作者：
Nachbagauer R;Kinzler D;Choi A;Hirsh A;Beaulieu E;Lecrenier N;Innis BL;Palese P;Mallett CP;Krammer F
通讯作者：
Krammer F
DOI：
10.1073/pnas.1414070111
发表时间：
2014-09-09
影响因子：
11.1
作者：
Ellebedy, Ali H.;Krammer, Florian;Ahmed, Rafi
通讯作者：
Ahmed, Rafi