Song Langzhou, Zhang Yi, Yun Nadezhda E, Poussard Allison L, Smith Jeanon N, Smith Jennifer K, Borisevich Viktoriya, Linde Jenna J, Zacks Michele A, Li Hong, Kavita Uma, Reiserova Lucia, Liu Xiangyu, Dumuren Kunmi, Balasubramanian Bhuvaneswari, Weaver Bruce, Parent Jason, Umlauf Scott, Liu Ge, Huleatt Jim, Tussey Lynda, Paessler Slobodan
VaxInnate Corporation, 3 Cedar Brook Drive, Cranbury, NJ 08512-0026, USA.
Vaccine. 2009 Sep 25;27(42):5875-84. doi: 10.1016/j.vaccine.2009.07.060. Epub 2009 Aug 3.
Transmission of highly pathogenic avian influenza (HPAI) between birds and humans is an ongoing threat that holds potential for the emergence of a pandemic influenza strain. A major barrier to an effective vaccine against avian influenza has been the generally poor immunopotency of many of the HPAI strains coupled with the manufacturing constraints employing conventional methodologies. Fusion of flagellin, a toll-like receptor-5 ligand, to vaccine antigens has been shown to enhance the immune response to the fused antigen in preclinical studies. Here, we have evaluated the immunogenicity and efficacy of a panel of flagellin-based hemagglutinin (HA) globular head fusion vaccines in inbred mice. The HA globular head of these vaccines is derived from the A/Vietnam/1203/04 (VN04; H5N1) HA molecule. We find that replacement of domain D3 of flagellin with the VN04 HA globular head creates a highly effective vaccine that elicits protective HAI titers which protect mice against disease and death in a lethal challenge model.
高致病性禽流感（HPAI）在鸟类与人类之间的传播是一个持续存在的威胁，有可能引发大流行性流感毒株。针对禽流感的有效疫苗面临的一个主要障碍是，许多高致病性禽流感毒株的免疫效力普遍较差，同时采用传统方法存在生产限制。在临床前研究中，鞭毛蛋白（一种Toll样受体5配体）与疫苗抗原融合已显示可增强对融合抗原的免疫反应。在此，我们评估了一组基于鞭毛蛋白的血凝素（HA）球状头部融合疫苗在近交系小鼠中的免疫原性和效力。这些疫苗的HA球状头部源自A/越南/1203/04（VN04；H5N1）HA分子。我们发现，用VN04 HA球状头部替换鞭毛蛋白的D3结构域可产生一种高效疫苗，该疫苗可引发保护性血凝抑制（HAI）滴度，在致死性攻毒模型中保护小鼠免受疾病和死亡。
