Vaccine and Infectious Disease Organization - International Vaccine Center (VIDO-InterVac), University of Saskatchewan, Saskatoon, Canada; Department of Veterinary Microbiology, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, Canada.
Vaccine and Infectious Disease Organization - International Vaccine Center (VIDO-InterVac), University of Saskatchewan, Saskatoon, Canada.
Vaccine. 2020 Feb 28;38(10):2387-2395. doi: 10.1016/j.vaccine.2020.01.051. Epub 2020 Jan 31.
The highly pathogenic avian influenza (HPAI) H5N1 viruses and their spillover into the human population pose substantial economic and public health threats. Although antiviral drugs have some effect in treating influenza infection, vaccination is still the most effective intervention to prevent possible pandemic outbreaks. We have developed a novel H5 influenza vaccine to improve the world's pandemic preparedness. We produced a hemagglutinin (HA) of HPAI H5N1 virus A/Alberta/01/2014 (AB14) using both mammalian (m) and bacterial (b) expression systems. The purified recombinant proteins were formulated with a proprietary adjuvant (TriAdj) and their efficacy as vaccine candidates was evaluated in mice. Intramuscular delivery of two doses of TriAdj formulated mammalian expressed HA (m-HA/TriAdj) was shown to provide full protection against a lethal challenge of AB14 in mice. In contrast, bacterially expressed HA with TriAdj (b-HA/TriAdj), b-HA without adjuvant, and m-HA without adjuvant resulted in no protection in immunized mice. Furthermore, m-HA/TriAdj elicited significantly higher levels of balanced Th1 and Th2 responses and neutralizing antibody titres. All the mice in the m-HA/TriAdj group survived a lethal AB14 H5N1 challenge and showed no signs of disease or infection as demonstrated by no loss of body weight or detectable virus in the lungs. Our results suggest that m-HA formulated with TriAdj has potential to protect against pandemic H5N1 in the event of its cross over to the human host.
高致病性禽流感 (HPAI) H5N1 病毒及其向人类群体的溢出对经济和公共卫生构成了重大威胁。尽管抗病毒药物在治疗流感感染方面有一定效果,但疫苗接种仍然是预防可能的大流行爆发的最有效干预措施。我们开发了一种新型 H5 流感疫苗,以提高全球对大流行的准备。我们使用哺乳动物 (m) 和细菌 (b) 表达系统生产了高致病性禽流感 H5N1 病毒 A/Alberta/01/2014 (AB14) 的血凝素 (HA)。纯化的重组蛋白用专有的佐剂 (TriAdj) 配制,并在小鼠中评估其作为候选疫苗的功效。两剂 TriAdj 配制的哺乳动物表达 HA (m-HA/TriAdj) 的肌肉内给药被证明可在小鼠中完全保护免受 AB14 的致死性挑战。相比之下,用 TriAdj 配制的细菌表达 HA (b-HA/TriAdj)、没有佐剂的 b-HA 和没有佐剂的 m-HA 都不能在免疫接种的小鼠中提供保护。此外,m-HA/TriAdj 引起了更高水平的平衡 Th1 和 Th2 反应以及中和抗体滴度。所有接受 m-HA/TriAdj 治疗的小鼠都在致死性 AB14 H5N1 挑战中存活下来,没有出现疾病或感染的迹象,体重没有减轻,肺部也没有检测到病毒。我们的结果表明,在其跨越到人类宿主的情况下,用 TriAdj 配制的 m-HA 有可能预防大流行 H5N1。