Chimeric virus-like particles (VLPs) displaying H1, H3 and H5 haemagglutinins - construction and immunogenicity

病毒样颗粒（VLP）在体内引起强烈的免疫反应。我们已经开发了一种新的VLP系统，该系统允许生产含有比以前可能的大得多的尺寸的外来疫苗抗原的VLP，并且已经表明这些VLP在不使用佐剂的情况下在小鼠中引起强烈的免疫应答。这些VLP的容量大到足以容纳流感的最重要的疫苗抗原，血凝素（HA）分子。我们将测试VLP是否可以生产包含三种最重要的HA类型中的每一种-目前在人类中传播的H1和H3，以及被认为是大流行威胁的H5（禽类）。将测试VLP在小鼠中诱导中和抗体和细胞免疫应答的能力，以及保护雪貂免受流感感染的能力。如果成功，HA-VLP系统将提供一种方法，用于快速生产新的流感疫苗，使用大规模发酵技术，如B肝炎和许多其他疫苗，而不是鸡蛋或细胞培养物，用于目前的流感疫苗。

Virus-like particles (VLPs) provoke strong immune responses in the body. We have developed a novel VLP system that allows the production of VLPs containing foreign vaccine antigens of much larger size than previously possible, and have shown that these VLPs provoke strong immune responses in mice without the use of adjuvants. The capacity of these VLPs is large enough to accommodate the most important vaccine antigen of influenza, the haemagglutinin (HA) molecule. We will test whether VLPs can be produced containing each of the three most important HA types _ H1 and H3 that are currently circulating in man, and H5 (avian) that is considered a pandemic threat. VLPs will be tested for their ability to induce neutralizing antibody and cellular immune responses in mice, and for their ability to protect ferrets from influenza infection. If successful, the HA-VLP system would provide a method for the rapid production of new influenza vaccines using large-scale fermentation technology as for hepatitis B and many other vaccines, rather than eggs or cell culture as used for current influenza vaccines.