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.

人类乳头瘤病毒（HPV）导致全世界约5％的癌症病例。幸运的是，已批准了三种预防性疫苗来预防HPV感染。据预测，最新的HPV疫苗Gardasil-9可针对引起约90％的宫颈癌，86％的与HPV相关的阴茎癌和约93％的与HPV相关的头颈部癌的HPV类型提供保护。作为Gardasil-9的替代品，我们开发并测试了针对HPV次要衣壳蛋白L2中保守表位的新型候选疫苗。我们在噬菌体MS2病毒样颗粒（VLP）的表面上显示了串联的HPV31 / 16L2肽（氨基酸17-31）或HPV L2的共有肽（氨基酸69-86或108-122）。用展示了串联肽的MS2 VLP免疫或用展示了串联肽和共有肽69-86的VLP混合物免疫的小鼠引发了针对单个L2表位的高滴度抗体。此外，预防接种的小鼠受到HPV假病毒16、31、45、58的宫颈阴道感染，并且来自免疫小鼠的血清中和HPV假病毒18和33的水平与用Gardasil-9免疫的小鼠相似。这些结果表明，用串联L2肽或低价L2肽展示VLP混合物进行免疫可以提供针对多种HPV类型的广泛保护。58和来自免疫小鼠的血清中和HPV假病毒18和33的水平与用Gardasil-9免疫的小鼠相似。这些结果表明，用串联L2肽或低价展示L2肽的VLP混合物免疫可为多种HPV类型提供广泛的保护。58和来自免疫小鼠的血清中和HPV假病毒18和33的水平与用Gardasil-9免疫的小鼠相似。这些结果表明，用串联L2肽或低价展示L2肽的VLP混合物免疫可为多种HPV类型提供广泛的保护。