基於植物的四價病毒樣顆粒流感疫苗效價高、安全性好
作者：
小柯機器人發布時間：2020/10/17 23:05:04
加拿大Medicago生物製藥公司Nathalie Landry團隊研究了基於植物的四價流感病毒樣顆粒疫苗的有效性、免疫原性和安全性。2020年10月13日，該研究發表在《柳葉刀》雜誌上。
儘管有基於雞蛋胚的疫苗和其他疫苗，季節性流感仍然是重大的公共衛生威脅。基於植物製備可能會解決當前疫苗的某些局限性。研究組描述了在植物中製備的重組四價病毒樣顆粒（QVLP）流感疫苗的兩項3期臨床療效研究，一項涉及18-64歲的成年人（18-64歲研究），另一項涉及65歲及以上的老年人（65歲以上的研究）。
研究組進行了兩項隨機、無觀察員的多國跨國研究，2017-2018年在北半球的73個地點進行18-64歲研究，2018-2019年在北半球的104個地點進行65歲以上的研究，遍及亞洲、歐洲和北美。18-64歲研究招募BMI低於40 kg/m2、年齡為18-64歲、身體健康的參與者；65歲以上的研究招募為BMI低於35 kg/m2、年齡在65歲以上、不住在康復中心或養老院、沒有嚴重或不斷惡化的醫學問題的參與者。
2017年8月30日至2018年1月15日，18-64歲研究中10160名參與者被隨機分配（1：1），其中5077名接種QVLP疫苗，5083名接種安慰劑。2018年9月18日至2019年2月22日，65歲以上研究的12794名參與者被隨機分配（1：1），其中6396名接種QVLP疫苗，6398名接種四價滅活疫苗（QIV）。
18-64歲研究的主要結局是絕對疫苗效力，可以預防由實驗室確認的由抗原匹配的流感病毒株引起的呼吸道疾病。65歲以上研究的主要結局是相對疫苗效力，可預防由實驗室確認的任何流感毒株引起的流感樣疾病。
18-64歲研究中，QVLP組中4814名參與者和安慰劑組中4812名參與者被納入最終分析。該研究沒有達到QVLP疫苗（35.1%）對抗匹配菌株引起的呼吸系統疾病的70%絕對疫苗效力的主要結局。QVLP組的5064名參與者中有55名（1.1％），而安慰劑組的5072名中有51名（1％）發生嚴重不良事件；兩組分別有4名（0.1%）和6名（0.1%）參與者發生了與治療相關的嚴重不良事件。
65歲以上研究中，QVLP組中5996名參與者和QIV組中6026名參與者被納入最終分析。這項研究達到了主要非劣效性終點，即QVLP疫苗具有相對疫苗效力，可預防由8.8％的任何菌株引起的流感樣疾病。QVLP組的6352名參與者中有263名（4.1％），而QIV組的6366名參與者中有266名（4.2％）發生嚴重不良事件；兩組分別有1名（<0.1％）與3名（<0.1％）參與者發生了與治療相關的嚴重治療不良事件。
研究結果表明，植物來源的QVLP疫苗可為成年人的流感病毒引起的呼吸道疾病和類似流感的疾病提供重要的保護，兩組參與者的耐受性良好，未發生重大安全事件。
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