Infectious Disease Research Centre, CHUL, Laval University, 2705 boul. Laurier, Quebec city, PQ, G1V 4G2, Canada.
Vaccine. 2012 Mar 28;30(15):2535-42. doi: 10.1016/j.vaccine.2012.01.085. Epub 2012 Feb 8.
The principal caveat of existing influenza vaccine is their failure to provide long-term protection. This lack of efficiency is caused by persistent (drift) and dramatic (shift) antigenic changes on the major surface proteins, the main target of protective immunity generated by traditional vaccines. Alternatively, vaccination with most conserved protein, like the nucleoprotein (NP) can stimulate immunity against multiple serotypes and could potentially provides an extended protection. The NP antigen contains more than 90% protein sequence homology among influenza A isolates and it also contains dominant CTL targets epitopes that made this antigen an attractive target for developing universal vaccine. However, NP protein is a weak antigen and need the use of adjuvant to increase its immunogenicity. We have developed an innovative high avidity VLP (HAV) nanoparticle to improve its adjuvant property to the NP antigen. The nanoparticles are derived from papaya mosaic virus capsid protein (PapMV CP) produced in a bacteria expression system. We generated the HAV by adding an affinity peptide directed to the NP protein at the surface of the VLPs. The fusions of the affinity peptide to PapMV VLPs increased the avidity of PapMV VLPs to NP protein. This modification enhanced the humoral and the IFN-γ response directed to NP. Moreover, the immunity generated by the HAV adjuvanted NP vaccine improved the protection of vaccinated mice to a challenge with influenza virus. The protection was characterized by accelerated virus elimination after the onset of infection and rapid recovery of the vaccinated animals.
现有流感疫苗的主要缺点是它们不能提供长期保护。这种效率低下是由于主要表面蛋白（保护性免疫的主要目标）上持续（漂移）和显著（转变）的抗原变化引起的。另一方面，使用大多数保守的蛋白质（如核蛋白 (NP)）进行疫苗接种可以刺激针对多种血清型的免疫，并且可能提供延长的保护。NP 抗原在流感 A 分离株之间含有超过 90%的蛋白质序列同源性，它还含有优势 CTL 靶标表位，这使得该抗原成为开发通用疫苗的有吸引力的目标。然而，NP 蛋白是一种弱抗原，需要使用佐剂来提高其免疫原性。我们开发了一种创新的高亲和力 VLP（HAV）纳米颗粒，以提高其对 NP 抗原的佐剂特性。这些纳米颗粒源自木瓜花叶病毒衣壳蛋白 (PapMV CP)，由细菌表达系统产生。我们通过在 VLPs 表面添加一个针对 NP 蛋白的亲和肽来生成 HAV。亲和肽与 PapMV VLPs 的融合增加了 PapMV VLPs 对 NP 蛋白的亲和力。这种修饰增强了针对 NP 的体液和 IFN-γ 反应。此外，HAV 佐剂 NP 疫苗产生的免疫增强了接种小鼠对流感病毒攻击的保护。这种保护的特征是在感染开始后加速病毒清除和接种动物的快速恢复。
