加拿大Medicago生物制药公司Nathalie Landry团队研究了基于植物的四价流感病毒样颗粒疫苗的有效性、免疫原性和安全性。2020年10月13日，该研究发表在《柳叶刀》杂志上。

尽管有基于鸡蛋胚的疫苗和其他疫苗，季节性流感仍然是重大的公共卫生威胁。基于植物制备可能会解决当前疫苗的某些局限性。研究组描述了在植物中制备的重组四价病毒样颗粒（QVLP）流感疫苗的两项3期临床疗效研究，一项涉及18-64岁的成年人（18-64岁研究），另一项涉及65岁及以上的老年人（65岁以上的研究）。

研究组进行了两项随机、无观察员的多国跨国研究，2017-2018年在北半球的73个地点进行18-64岁研究，2018-2019年在北半球的104个地点进行65岁以上的研究，遍及亚洲、欧洲和北美。18-64岁研究招募BMI低于40 kg/m2、年龄为18-64岁、身体健康的参与者；65岁以上的研究招募为BMI低于35 kg/m2、年龄在65岁以上、不住在康复中心或养老院、没有严重或不断恶化的医学问题的参与者。

2017年8月30日至2018年1月15日，18-64岁研究中10160名参与者被随机分配（1：1），其中5077名接种QVLP疫苗，5083名接种安慰剂。2018年9月18日至2019年2月22日，65岁以上研究的12794名参与者被随机分配（1：1），其中6396名接种QVLP疫苗，6398名接种四价灭活疫苗（QIV）。
18-64岁研究的主要结局是绝对疫苗效力，可以预防由实验室确认的由抗原匹配的流感病毒株引起的呼吸道疾病。65岁以上研究的主要结局是相对疫苗效力，可预防由实验室确认的任何流感毒株引起的流感样疾病。

18-64岁研究中，QVLP组中4814名参与者和安慰剂组中4812名参与者被纳入最终分析。该研究没有达到QVLP疫苗（35.1%）对抗匹配菌株引起的呼吸系统疾病的70%绝对疫苗效力的主要结局。QVLP组的5064名参与者中有55名（1.1％），而安慰剂组的5072名中有51名（1％）发生严重不良事件；两组分别有4名（0.1%）和6名（0.1%）参与者发生了与治疗相关的严重不良事件。

65岁以上研究中，QVLP组中5996名参与者和QIV组中6026名参与者被纳入最终分析。这项研究达到了主要非劣效性终点，即QVLP疫苗具有相对疫苗效力，可预防由8.8％的任何菌株引起的流感样疾病。QVLP组的6352名参与者中有263名（4.1％），而QIV组的6366名参与者中有266名（4.2％）发生严重不良事件；两组分别有1名（<0.1％）与3名（<0.1％）参与者发生了与治疗相关的严重治疗不良事件。

研究结果表明，植物来源的QVLP疫苗可为成年人的流感病毒引起的呼吸道疾病和类似流感的疾病提供重要的保护，两组参与者的耐受性良好，未发生重大安全事件。

附：英文原文

Title: Efficacy, immunogenicity, and safety of a plant-derived, quadrivalent, virus-like particle influenza vaccine in adults (18–64 years) and older adults (≥65 years): two multicentre, randomised phase 3 trials

Author: Brian J Ward, Alexander Makarkov, Annie Séguin, Stéphane Pillet, Sonia Trépanier, Jiwanjeet Dhaliwall, Michael D Libman, Timo Vesikari, Nathalie Landry

Issue&Volume: 2020-10-13

Abstract:

Background

Seasonal influenza remains a substantial public health threat despite the availability of egg-derived and other vaccines. Plant-based manufacturing might address some of the limitations of current vaccines. We describe two phase 3 efficacy studies of a recombinant quadrivalent virus-like particle (QVLP) influenza vaccine manufactured in plants, one in adults aged 18–64 years (the 18–64 study) and one in older people aged 65 years and older (the 65-plus study).

Methods

We did two randomised, observer-blind, multinational studies in the northern hemisphere in the 2017–18 (the 18–64 study) and 2018–19 (the 65-plus study) influenza seasons. The 18–64 study was done at 73 sites and the 65-plus study was done at 104 sites, both across Asia, Europe, and North America. In the 18–64 study, inclusion criteria were body-mass index less than 40 kg/m 2; age 18–64 years at screening visit; and good health. In the 65-plus study, inclusion criteria were body-mass index of maximum 35 kg/m 2; aged 65 years or older at screening visit; not living in a rehabilitation centre or care home; and no acute or evolving medical problems. Participants in the 18–64 study were randomly assigned (1:1) to receive either QVLP vaccine (30 μg haemagglutinin per strain) or placebo. Participants in the 65-plus study were randomly assigned (1:1) to receive QVLP vaccine (30 μg haemagglutinin per strain) or quadrivalent inactivated vaccine (QIV; 15 μg haemagglutinin per strain). The primary outcome in the 18–64 study was absolute vaccine efficacy to prevent laboratory-confirmed, respiratory illness caused by antigenically matched influenza strains. The primary outcome in the 65-plus study was relative vaccine efficacy to prevent laboratory-confirmed influenza-like illness caused by any influenza strain. The primary analyses were done in the per-protocol population and safety was assessed in all participants who received the assigned treatment. These studies are registered with ClinicalTrials.gov (18–64 study NCT03301051; 65-plus study NCT03739112).

Findings

In the 18–64 study, between Aug 30, 2017, and Jan 15, 2018, 10160 participants were randomly assigned to receive either QVLP vaccine (5077 participants) or placebo (5083 participants). The per-protocol population consisted of 4814 participants in the QVLP group and 4812 in the placebo group. The study did not meet its primary endpoint of 70% absolute vaccine efficacy for the QVLP vaccine (35·1% [95% CI 17·9 to 48·7]) against respiratory illness caused by matched strains. 55 (1·1%) of 5064 participants in the QVLP group versus 51 (1·0%) of 5072 in the placebo group had a serious adverse event. Four (0·1%) and six [0·1%] participants had severe treatment-related treatment-emergent adverse events. In the 65-plus study, between Sept 18, 2018, and Feb 22, 2019, 12794 participants were randomly assigned to receive either QVLP vaccine (6396 participants) or QIV (6398 participants). The per-protocol population consisted of 5996 participants in the QVLP group and 6026 in the QIV group. The study met its primary non-inferiority endpoint with a relative vaccine efficacy of the QVLP vaccine for the prevention of influenza-like illness caused by any strain of 8·8% (16·7 to 28·7). 263 (4·1%) of 6352 participants in the QVLP group versus 266 (4·2%) of 6366 in the QIV group had serious adverse events (one [<0·1%] vs two [<0·1%] were considered treatment-related); one (<0·1%) versus three (<0·1%) participants had severe treatment-related treatment-emergent adverse events.

Interpretation

These efficacy studies are the first large-scale studies of any plant-derived human vaccine. Together, they show that the plant-derived QVLP vaccine can provide substantial protection against respiratory illness and influenza-like illness caused by influenza viruses in adults. QVLP vaccine was well tolerated and no major safety signal arose in participants who received QVLP vaccine across the two studies.

DOI: 10.1016/S0140-6736(20)32014-6

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)32014-6/fulltext