An influenza hemagglutinin stem nanoparticle vaccine induces cross-group 1 neutralizing antibodies in healthy adults.
An influenza hemagglutinin stem nanoparticle vaccine induces cross-group 1 neutralizing antibodies in healthy adults.
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DOI：
10.1126/scitranslmed.ade4790
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发表时间：
2023-04-19
影响因子：
17.1
通讯作者：
Ledgerwood, Julie E.
中科院分区：
文献类型：
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作者：
Widge, Alicia T.;Hofstetter, Amelia R.;V. Houser, Katherine;Awan, Seemal F.;Chen, Grace L.;Florez, Maria C. Burgos;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.
流感疫苗可以通过诱导交叉反应免疫的平台来改进。目前许可的疫苗中流感血凝素（HA）头部的免疫优势阻碍了交叉反应中和的干细胞定向抗体的诱导。没有可变血凝素头部结构域的疫苗有可能将免疫反应集中在保守的血凝素干细胞上。这项首次人体剂量递增开放标签1期临床试验（NCT03814720）测试了一种基于A/New Caledonia/20/1999的H1 HA干细胞的HA稳定干细胞铁蛋白纳米颗粒疫苗（H1ssF）。52名年龄在18至70岁之间的健康成年人被招募，接受一次20 μg的H1ssF （n = 5）或两次60 μg的H1ssF (n = 47)，初始-增强间隔为16周。35名（74%）60 μg剂量的参与者接种了加强疫苗，而11名（23%）由于COVID-19大流行早期的公共卫生限制而错过了加强疫苗接种。该试验的主要目的是评估H1ssF的安全性和耐受性，次要目的是评估疫苗接种后的抗体反应。H1ssF安全且耐受性良好，具有轻度的局部和全身反应性。最常见的症状包括注射部位疼痛或压痛（n = 10, 19%）、头痛（n = 10, 19%）和不适（n = 6, 12%）。我们发现，尽管先前有H1亚型头部特异性免疫，但H1ssF引发了针对1组流感病毒保守HA干的交叉反应性中和抗体。这些反应是持久的，在接种疫苗后1年多观察到中和抗体。我们的研究结果支持这个平台在开发通用流感疫苗方面向前迈出了一步。
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.
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影响因子：
--
作者：
Bodewes, R.;De Mutsert, G.;Rimmelzwaan, G. F.
通讯作者：
Rimmelzwaan, G. F.
影响因子：
82.9
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.
通讯作者：
Ledgerwood, Julie E.
影响因子：
3.7
作者：
Russell, RJ;Gamblin, SJ;Skehel, JJ
通讯作者：
Skehel, JJ
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
影响因子：
5.4
作者：
Margine, Irina;Hai, Rong;Krammer, Florian
通讯作者：
Krammer, Florian