当前一代的季节性流感疫苗的药效,因需要利用过时的和费时的技术来生产新疫苗、以应对迅速变化的病毒而受到限制。这项研究提出了流感疫苗接种的一个新方法:利用融合到天然病毒附着蛋白“血凝素”上的自组装的、基于“铁蛋白”的纳米颗粒。“血凝素-纳米颗粒”疫苗被发现诱导中和抗体,对各种病毒亚型的免疫力高于某种获准上市的流感疫苗。例如,由一种1999年的“血凝素-纳米颗粒”疫苗诱发的抗体中和了从1934年到2007年的H1N1病毒,保护雪貂不被2007年的H1N1病毒感染。(生物谷Bioon.com)
生物谷推荐英文摘要:
Nature doi:10.1038/nature12202
Self-assembling influenza nanoparticle vaccines elicit broadly neutralizing H1N1 antibodies
Masaru Kanekiyo, Chih-Jen Wei, Hadi M. Yassine, Patrick M. McTamney, Jeffrey C. Boyington, James R. R. Whittle, Srinivas S. Rao, Wing-Pui Kong, Lingshu Wang & Gary J. Nabel
Influenza viruses pose a significant threat to the public and are a burden on global health systems1, 2. Each year, influenza vaccines must be rapidly produced to match circulating viruses, a process constrained by dated technology and vulnerable to unexpected strains emerging from humans and animal reservoirs. Here we use knowledge of protein structure to design self-assembling nanoparticles that elicit broader and more potent immunity than traditional influenza vaccines. The viral haemagglutinin was genetically fused to ferritin, a protein that naturally forms nanoparticles composed of 24 identical polypeptides3. Haemagglutinin was inserted at the interface of adjacent subunits so that it spontaneously assembled and generated eight trimeric viral spikes on its surface. Immunization with this influenza nanoparticle vaccine elicited haemagglutination inhibition antibody titres more than tenfold higher than those from the licensed inactivated vaccine. Furthermore, it elicited neutralizing antibodies to two highly conserved vulnerable haemagglutinin structures that are targets of universal vaccines: the stem4, 5 and the receptor binding site on the head6, 7. Antibodies elicited by a 1999 haemagglutinin–nanoparticle vaccine neutralized H1N1 viruses from 1934 to 2007 and protected ferrets from an unmatched 2007 H1N1 virus challenge. This structure-based, self-assembling synthetic nanoparticle vaccine improves the potency and breadth of influenza virus immunity, and it provides a foundation for building broader vaccine protection against emerging influenza viruses and other pathogens.