BACKGROUND: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). METHODS: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 (15 μg, 45 μg and 90 μg) 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). RESULTS: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 μg non-adjuvanted HAC1 vaccine group after the second vaccine dose (78% and 100%, respectively). CONCLUSIONS: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.

译文

背景: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,植物已用于生产重组蛋白,包括亚单位疫苗。一种基于亚型流感疫苗,HAC1,其基于来自2009年大流行性A / California / 04/2009(H1N1)流感病毒株的重组血凝素,已经在基于烟草的本氏烟草中使用基于植物病毒的瞬时表达技术进行了生产。在临床前研究中具有免疫原性和安全性(Shoji等,2011)。
方法:进行了一项首次在人体内的1期,单中心,随机,安慰剂对照,单盲,剂量递增研究,以研究在三种递增剂量水平(15μg)下HAC1制剂的安全性,反应原性和免疫原性(含45μg和90μg)含和不含Alhydrogel(®)的健康成年人(年龄在18至50岁之间)。将80名参与者随机分为6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。收件人接受两剂疫苗或安慰剂(单价H1N1疫苗队列除外,后者接受单剂疫苗,随后再接受一剂安慰剂)。
结果:该实验疫苗安全且耐受性良好,与安慰剂和已批准的单价H1N1疫苗相当。注射后唯一的局部反应是注射部位的疼痛和压痛。几乎所有不良事件的严重程度均为轻度至中度。在第二次疫苗接种后的90μg非佐剂HAC1疫苗组中,基于血清血凝抑制和病毒微中和抗体滴度,HAC1疫苗也是具有免疫原性的,具有最高的血清转化率(分别为78%和100%)。
结论:这是第一项证明健康成人中植物产生的H1N1亚单位流感疫苗的安全性和免疫原性的研究。结果支持对HAC1疫苗的进一步临床研究,并证明了基于植物的技术生产疫苗抗原的可行性。

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