Research Program Infection and Cancer, German Cancer Research Center, Heidelberg, Germany.
PLoS One. 2012;7(6):e39741. doi: 10.1371/journal.pone.0039741. Epub 2012 Jun 27.
The human papillomavirus (HPV) minor capsid protein L2 is a promising candidate for a broadly protective HPV vaccine yet the titers obtained in most experimental systems are rather low. Here we examine the potential of empty AAV2 particles (AAVLPs), assembled from VP3 alone, for display of L2 epitopes to enhance their immunogenicity. Insertion of a neutralizing epitope (amino acids 17-36) from L2 of HPV16 and HPV31 into VP3 at positions 587 and 453, respectively, permitted assembly into empty AAV particles (AAVLP(HPV16/31L2)). Intramuscularly vaccination of mice and rabbits with AAVLP(HPV16/31L2)s in montanide adjuvant, induced high titers of HPV16 L2 antibodies as measured by ELISA. Sera obtained from animals vaccinated with the AAVLP(HPV16/31L2)s neutralized infections with several HPV types in a pseudovirion infection assay. Lyophilized AAVLP(HPV16/31L2) particles retained their immunogenicity upon reconstitution. Interestingly, vaccination of animals that were pre-immunized with AAV2--simulating the high prevalence of AAV2 antibodies in the population--even increased cross neutralization against HPV31, 45 and 58 types. Finally, passive transfer of rabbit antisera directed against AAVLP(HPV16/31L2)s protected naïve mice from vaginal challenge with HPV16 pseudovirions. In conclusion, AAVLP(HPV16/31L2) particles have the potential as a broadly protective vaccine candidate regardless of prior exposure to AAV.
人乳头瘤病毒（HPV）的次要衣壳蛋白 L2 是一种有前途的广泛保护 HPV 疫苗候选物，但在大多数实验系统中获得的滴度相当低。在这里，我们研究了空腺相关病毒 2 颗粒（AAVLPs）的潜力，这些颗粒仅由 VP3 组装而成，用于展示 L2 表位以增强其免疫原性。将 HPV16 和 HPV31 的 L2 中的中和表位（氨基酸 17-36）分别插入 VP3 的位置 587 和 453，允许组装成空的 AAV 颗粒（AAVLP(HPV16/31L2)）。在 Montanide 佐剂中肌肉内接种 AAVLP(HPV16/31L2)s，可诱导高滴度的 HPV16 L2 抗体，如 ELISA 所示。用 AAVLP(HPV16/31L2)s 免疫的动物的血清在假病毒感染测定中中和了几种 HPV 型的感染。冻干的 AAVLP(HPV16/31L2)颗粒在重构后保留其免疫原性。有趣的是，用 AAV2 预先免疫的动物（模拟人群中 AAV2 抗体的高流行率）接种疫苗甚至增加了对 HPV31、45 和 58 型的交叉中和。最后，针对 AAVLP(HPV16/31L2)的兔抗血清的被动转移可保护未致敏的小鼠免受 HPV16 假病毒的阴道攻击。总之，AAVLP(HPV16/31L2)颗粒具有作为广泛保护疫苗候选物的潜力，而与先前是否暴露于 AAV 无关。
