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

病毒样颗粒(VLP)会在体内引发强烈的免疫反应。我们已经开发了一种新的VLP系统，它允许生产含有比以前可能的更大尺寸的外来疫苗抗原的VLP，并且已经证明这些VLP在不使用佐剂的情况下在小鼠身上激发强烈的免疫反应。这些VLP的容量足以容纳流感最重要的疫苗抗原-血凝素(HA)分子。我们将测试是否可以生产包含目前在人类中传播的三种最重要的甲型H1型和H3型以及被认为是大流行威胁的H5(禽流感)中的每一种类型的VLP。将测试VLP在小鼠中诱导中和抗体和细胞免疫反应的能力，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，使用大规模发酵技术快速生产新的流感疫苗，就像处理乙肝和许多其他疫苗一样，而不是像目前的流感疫苗那样使用鸡蛋或细胞培养。

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.