Safety and immunogenicity of a plant-produced recombinant monomer hemagglutinin-based influenza vaccine derived from influenza A (H1N1)pdm09 virus: a Phase 1 dose-escalation study in healthy adults.
Safety and immunogenicity of a plant-produced recombinant monomer hemagglutinin-based influenza vaccine derived from influenza A (H1N1)pdm09 virus: a Phase 1 dose-escalation study in healthy adults.
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DOI：
10.1016/j.vaccine.2013.10.017
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发表时间：
2014-04-17
期刊：
影响因子：
5.5
通讯作者：
Fraunhofer USA Center for Molecular Biotechnology Study Group
中科院分区：
文献类型：
--
作者：
Cummings JF;Guerrero ML;Moon JE;Waterman P;Nielsen RK;Jefferson S;Gross FL;Hancock K;Katz JM;Yusibov V;Fraunhofer USA Center for Molecular Biotechnology Study Group
新型流感病毒继续在全球范围内构成潜在的大流行威胁。近年来，植物已被用于生产重组蛋白，包括亚单位疫苗。基于来自流感病毒的2009年大流行A/加州/04/2009（H1N1）毒株的重组血凝素的亚单位流感疫苗，HAC 1，已经使用基于植物病毒的瞬时表达技术在本氏烟草植物中制造，并且在临床前研究中证明是免疫原性和安全的（Shoji et al.，2011年）。进行了首次人体、1期、单中心、随机、安慰剂对照、单盲、剂量递增研究，以在18-50岁（含）的健康成年人中研究具有和不具有Alhydrogel®的三个递增剂量水平（15μg、45μg和90μg）的HAC 1制剂的安全性、反应原性和免疫原性。80名参与者被随机分为六个研究疫苗组，一个生理盐水安慰剂组和一个批准的单价H1N1疫苗组。接受者接受两剂疫苗或安慰剂（单价H1N1疫苗队列除外，该队列接受单剂疫苗，随后接受一剂安慰剂）。实验疫苗是安全的，耐受性良好，与安慰剂和批准的单价H1N1疫苗相当。注射部位疼痛和压痛是接种后报告的唯一局部征集性反应。几乎所有不良事件的严重程度均为轻度至中度。在第二次接种疫苗后，基于血清血凝抑制和病毒微量中和抗体滴度，90 g无佐剂的HAC 1疫苗组中，HAC 1疫苗也具有免疫原性，血清转化率最高（分别为78%和100%）。这是第一项证明植物生产的亚单位H1N1流感疫苗在健康成人中的安全性和免疫原性的研究。这些结果支持进一步的临床研究，并证明了基于植物的疫苗抗原生产技术的可行性。
Novel influenza viruses continue to pose a potential pandemic threat worldwide. In recent years, plants have been used to produce recombinant proteins, including subunit vaccines. A subunit influenza vaccine, HAC1, based on recombinant hemagglutinin from the 2009 pandemic A/California/04/2009 (H1N1) strain of influenza virus, has been manufactured using a plant virus-based transient expression technology in Nicotiana benthamiana plants and demonstrated to be immunogenic and safe in pre-clinical studies (Shoji et al., 2011). A first-in-human, Phase 1, single-center, randomized, placebo-controlled, single-blind, dose escalation study was conducted to investigate safety, reactogenicity and immunogenicity of an HAC1 formulation at three escalating dose levels (15μg, 45μg and 90μg) with and without Alhydrogel®, in healthy adults 18–50 years of age (inclusive). Eighty participants were randomized into six study vaccine groups, a saline placebo group and an approved monovalent H1N1 vaccine group. Recipients received two doses of vaccine or placebo (except for the monovalent H1N1 vaccine cohort, which received a single dose of vaccine, later followed by a dose of placebo). The experimental vaccine was safe and well tolerated, and comparable to placebo and the approved monovalent H1N1 vaccine. Pain and tenderness at the injection site were the only local solicited reactions reported following vaccinations. Nearly all adverse events were mild to moderate in severity. The HAC1 vaccine was also immunogenic, with the highest seroconversion rates, based on serum hemagglutination-inhibition and virus microneutralization antibody titers, in the 90 g non-adjuvanted HAC1 vaccine group after the second vaccine dose (78% and 100%, respectively). This is the first study demonstrating the safety and immunogenicity of a plant-produced subunit H1N1 influenza vaccine in healthy adults. The results support further clinical investigation of the HAC1 vaccine as well as demonstrate the feasibility of the plant-based technology for vaccine antigen production.
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