Honda-Okubo Yoshikazu, Rajapaksha Harinda, Sajkov Dimitar, Gordon David, Cox Manon M J, Petrovsky Nikolai
a Vaxine Pty Ltd, Flinders Medical Centre , Adelaide , Australia.
b Department of Endocrinology , Flinders University , Adelaide , Australia.
Hum Vaccin Immunother. 2017 Jun 3;13(6):1-11. doi: 10.1080/21645515.2017.1279765. Epub 2017 Feb 14.
Timely vaccine supply is critical during influenza pandemics but is impeded by current virus-based manufacturing methods. The 2009 H1N1/2009pdm 'swine flu' pandemic reinforced the need for innovation in pandemic vaccine design. We report on insights gained during rapid development of a pandemic vaccine based on recombinant haemagglutinin (rHA) formulated with Advax™ delta inulin adjuvant (Panblok-H1/Advax). Panblok-H1/Advax was designed and manufactured within 1 month of the pandemic declaration by WHO and successfully entered human clinical testing in under 3 months from first isolation and sequencing of the novel pandemic virus, requiring several major challenges to be overcome. Panblok-H1/Advax successfully induced neutralising antibodies against the pandemic strain, but also induced cross-neutralising antibodies in a subset of subjects against an H1N1 strain (A/Puerto Rico/8/34) derived from the 1918 Spanish flu, highlighting the possibility to use Advax to induce more broadly cross-protective antibody responses. Interestingly, the rHA from H1N1/2009pdm exhibited variants in the receptor binding domain that had a major impact on receptor binding and hemagglutination ability. We used an in silico structural modeling approach to better understand the unusual behavior of the novel hemagglutinin, thereby demonstrating the power of computational modeling approaches for rapid characterization of new pandemic viruses. While challenges remain in ensuring ultrafast vaccine access for the entire population in response to future pandemics, the adjuvanted recombinant Panblok-H1/Advax vaccine proved its utility during a real-life pandemic situation.
在流感大流行期间，及时供应疫苗至关重要，但目前基于病毒的生产方法阻碍了这一目标的实现。2009年甲型H1N1流感（2009pdm）“猪流感”大流行凸显了大流行疫苗设计创新的必要性。我们报告了在基于重组血凝素（rHA）与Advax™ δ-菊粉佐剂（Panblok-H1/Advax）配制的大流行疫苗快速研发过程中获得的见解。Panblok-H1/Advax在世界卫生组织宣布大流行后的1个月内设计并生产出来，并在新型大流行病毒首次分离和测序后的3个月内成功进入人体临床试验，这需要克服几个重大挑战。Panblok-H1/Advax成功诱导了针对大流行毒株的中和抗体，而且在一部分受试者中还诱导了针对源自1918年西班牙流感的H1N1毒株（A/波多黎各/8/34）的交叉中和抗体，这凸显了使用Advax诱导更广泛交叉保护性抗体反应的可能性。有趣的是，来自2009pdm H1N1的rHA在受体结合域表现出变异，这对受体结合和血凝能力产生了重大影响。我们使用计算机结构建模方法来更好地理解新型血凝素的异常行为，从而证明了计算建模方法在快速表征新型大流行病毒方面的作用。尽管在确保全体人群能够在未来大流行时超快获得疫苗方面仍存在挑战，但佐剂重组Panblok-H1/Advax疫苗在实际大流行情况下证明了其效用。
