Department of Biological Sciences, Michigan Technological University, Houghton, MI 49931, USA.
Department of Molecular Genetics and Microbiology, University of New Mexico School of Medicine, Albuquerque, NM 87131, USA.
Antiviral Res. 2017 Nov;147:116-123. doi: 10.1016/j.antiviral.2017.09.012. Epub 2017 Sep 20.
Human papillomaviruses (HPVs) cause approximately 5% of cancer cases worldwide. Fortunately, three prophylactic vaccines have been approved to protect against HPV infections. Gardasil-9, the most recent HPV vaccine, is predicted to offer protection against the HPV types that cause ∼90% of cervical cancer, 86% of HPV-associated penile cancers, and ∼93% of HPV-associated head & neck cancers. As an alternative to Gardasil-9, we developed and tested a novel candidate vaccine targeting conserved epitopes in the HPV minor capsid protein, L2. We displayed a tandem HPV31/16L2 peptide (amino acid 17-31) or consensus peptides from HPV L2 (amino acid 69-86 or 108-122) on the surface of bacteriophage MS2 virus-like particles (VLPs). Mice immunized with the MS2 VLPs displaying the tandem peptide or immunized with a mixture of VLPs (displaying the tandem peptide and consensus peptide 69-86) elicited high titer antibodies against individual L2 epitopes. Moreover, vaccinated mice were protected from cervicovaginal infection with HPV pseudoviruses 16, 31, 45, 58 and sera from immunized mice neutralized HPV pseudoviruses 18 and 33 at levels similar to mice immunized with Gardasil-9. These results suggest that immunization with a tandem, L2 peptide or a low valency mixture of L2 peptide-displaying VLPs can provide broad protection against multiple HPV types.
人乳头瘤病毒（HPV）导致全球约 5%的癌症病例。幸运的是，已经批准了三种预防性疫苗来预防 HPV 感染。Gardasil-9 是最新的 HPV 疫苗，预计能预防导致约 90%宫颈癌、86%HPV 相关阴茎癌和约 93%HPV 相关头颈部癌的 HPV 型别。作为 Gardasil-9 的替代品，我们开发并测试了一种针对 HPV 次要衣壳蛋白 L2 保守表位的新型候选疫苗。我们在噬菌体 MS2 病毒样颗粒（VLPs）表面展示了串联的 HPV31/16L2 肽（氨基酸 17-31）或来自 HPV L2 的共有肽（氨基酸 69-86 或 108-122）。用 MS2 VLPs 展示串联肽或用包含 VLPs（展示串联肽和共有肽 69-86）的混合物免疫的小鼠，可针对个别 L2 表位产生高滴度的抗体。此外，接种疫苗的小鼠可免受 HPV 假病毒 16、31、45、58 的宫颈阴道感染，免疫血清可中和 HPV 假病毒 18 和 33 的滴度与接种 Gardasil-9 的小鼠相似。这些结果表明，用串联的 L2 肽或含有 L2 肽展示 VLPs 的低价混合物免疫可提供针对多种 HPV 型别的广泛保护。
