Kuck Dirk, Lau Tobias, Leuchs Barbara, Kern Andrea, Müller Martin, Gissmann Lutz, Kleinschmidt Jürgen A
Infection and Cancer Programme, German Cancer Research Center, Heidelberg, Germany.
J Virol. 2006 Mar;80(6):2621-30. doi: 10.1128/JVI.80.6.2621-2630.2006.
Adeno-associated viruses (AAV) have been developed and evaluated as recombinant vectors for gene therapy in many preclinical studies, as well as in clinical trials. However, only a few approaches have used recombinant AAV (rAAV) to deliver vaccine antigens. We generated an rAAV encoding the major capsid protein L1 (L1h) from the human papillomavirus type 16 (HPV16), aiming to develop a prophylactic vaccine against HPV16 infections, which are the major cause of cervical cancer in women worldwide. A single dose of rAAV5 L1h administered intranasally was sufficient to induce high titers of L1-specific serum antibodies, as well as mucosal antibodies in vaginal washes. Seroconversion was maintained for at least 1 year. In addition, a cellular immune response was still detectable 60 weeks after immunization. Furthermore, lyophilized rAAV5 L1h successfully evoked a systemic and mucosal immune response in mice. These data clearly show the efficacy of a single-dose intranasal immunization against HPV16 based on the recombinant rAAV5L1h vector without the need of an adjuvant.
腺相关病毒（AAV）已在许多临床前研究以及临床试验中作为基因治疗的重组载体得到开发和评估。然而，只有少数方法使用重组AAV（rAAV）来递送疫苗抗原。我们构建了一种编码人乳头瘤病毒16型（HPV16）主要衣壳蛋白L1（L1h）的rAAV，旨在开发一种预防HPV16感染的预防性疫苗，HPV16感染是全球女性宫颈癌的主要病因。经鼻内给予单剂量的rAAV5 L1h足以诱导高滴度的L1特异性血清抗体以及阴道灌洗液中的黏膜抗体。血清转化至少维持1年。此外，免疫后60周仍可检测到细胞免疫反应。此外，冻干的rAAV5 L1h在小鼠中成功引发了全身和黏膜免疫反应。这些数据清楚地表明了基于重组rAAV5L1h载体的单剂量鼻内免疫对HPV16的有效性，且无需佐剂。
