Pillet S, Racine T, Nfon C, Di Lenardo T Z, Babiuk S, Ward B J, Kobinger G P, Landry N
Medicago Inc., 1020 Route de l'Église, Bureau 600, Québec, QC, Canada; Research Institute of the McGill University Health Center, Montreal, QC, Canada.
Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB, Canada.
Vaccine. 2015 Nov 17;33(46):6282-9. doi: 10.1016/j.vaccine.2015.09.065. Epub 2015 Oct 2.
In March 2013, the Chinese Centre for Disease Control and Prevention confirmed the first reported case of human infection with an avian influenza A H7N9 virus. Infection with this virus often caused severe pneumonia and acute respiratory distress syndrome resulting in a case fatality rate >35%. The risk of pandemic highlighted, once again, the need for a more rapid and scalable vaccine response capability. Here, we describe the rapid (19 days) development of a plant-derived VLP vaccine based on the hemagglutinin sequence of influenza H7N9 A/Hangzhou/1/2013. The immunogenicity of the H7 VLP vaccine was assessed in mice and ferrets after one or two intramuscular dose(s) with and without adjuvant (alum or GLA-SE™). In ferrets, we also measured H7-specific cell-mediated immunity. The mice and ferrets were then challenged with H7N9 A/Anhui/1/2013 influenza virus. A single immunization with the adjuvanted vaccine elicited a strong humoral response and protected mice against an otherwise lethal challenge. Two doses of unadjuvanted vaccine significantly increased humoral response and resulted in 100% protection with significant reduction of clinical signs leading to nearly asymptomatic infections. In ferrets, a single immunization with the alum-adjuvanted H7 VLP vaccine induced strong humoral and CMI responses with antigen-specific activation of CD3(+) T cells. Compared to animals injected with placebo, ferrets vaccinated with alum-adjuvanted vaccine displayed no weight loss during the challenge. Moreover, the vaccination significantly reduced the viral load in lungs and nasal washes 3 days after the infection. This candidate plant-made H7 vaccine therefore induced protective responses after either one adjuvanted or two unadjuvanted doses. Studies are currently ongoing to better characterize the immune response elicited by the plant-derived VLP vaccines. Regardless, these data are very promising for the rapid production of an immunogenic and protective vaccine against this potentially pandemic virus.
2013年3月,中国疾病预防控制中心确认了首例人感染甲型H7N9禽流感病毒的报告病例。感染该病毒常导致严重肺炎和急性呼吸窘迫综合征,病死率超过35%。这种大流行风险再次凸显了对更快速、可扩展的疫苗应对能力的需求。在此,我们描述了一种基于甲型H7N9流感病毒A/杭州/1/2013血凝素序列的植物源病毒样颗粒(VLP)疫苗的快速(19天)研发过程。在小鼠和雪貂中,对给予或未给予佐剂(明矾或GLA-SE™)的一或两剂肌肉注射后的H7 VLP疫苗的免疫原性进行了评估。在雪貂中,我们还检测了H7特异性细胞介导免疫。然后用甲型H7N9流感病毒A/安徽/1/2013对小鼠和雪貂进行攻毒。单剂量接种佐剂疫苗可引发强烈的体液反应,并保护小鼠免受致死性攻毒。两剂未加佐剂的疫苗显著增强了体液反应,实现了100%的保护,且临床症状显著减轻,导致几乎无症状感染。在雪貂中,单剂量接种明矾佐剂的H7 VLP疫苗可诱导强烈的体液和细胞介导免疫反应,以及CD3(+) T细胞的抗原特异性激活。与注射安慰剂的动物相比,接种明矾佐剂疫苗的雪貂在攻毒期间体重未减轻。此外,接种疫苗在感染后3天显著降低了肺部和鼻腔冲洗液中的病毒载量。因此,这种候选植物源H7疫苗在单剂量佐剂或两剂未加佐剂接种后均可诱导保护性反应。目前正在进行研究,以更好地表征植物源VLP疫苗引发的免疫反应。无论如何,这些数据对于快速生产针对这种潜在大流行病毒的免疫原性和保护性疫苗非常有前景。
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