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Abstract：
Vaccines targeting conserved epitopes in the HPV minor capsid protein, L2, can elicit antibodies that can protect against a broad spectrum of HPV types that are associated with cervical cancer and other HPV malignancies. Thus, L2 vaccines have been explored as alternatives to the current HPV vaccines, which are largely type-specific. In this study we assessed the immunogenicity of peptides spanning the N-terminal domain of L2 linked to the surface of a highly immunogenic bacteriophage virus-like particle (VLP) platform. Although all of the HPV16 L2 peptide-displaying VLPs elicited high-titer anti-peptide antibody responses, only a subset of the immunogens elicited antibody responses that were strongly protective from HPV16 pseudovirus (PsV) infection in a mouse genital challenge model. One of these peptides, mapping to HPV16 L2 amino acids 65-85, strongly neutralized HPV16 PsV but showed little ability to cross-neutralize other high-risk HPV types. In an attempt to broaden the protection generated through vaccination with this peptide, we immunized mice with VLPs displaying a peptide that represented a consensus sequence from high-risk and other HPV types. Vaccinated mice produced antibodies with broad, high-titer neutralizing activity against all of the HPV types that we tested. Therefore, immunization with virus-like particles displaying a consensus HPV sequence is an effective method to broaden neutralizing antibody responses against a type-specific epitope.
摘要：
针对HPV次要衣壳蛋白中保守表位的疫苗，L2可以引发可以针对与宫颈癌和其他HPV恶性肿瘤相关的广谱HPV类型进行保护的抗体。因此，L2疫苗已被探索作为目前HPV疫苗的替代品，它们在很大程度上是特定类型的。在这项研究中，我们评估了跨越L2N末端结构域的肽的免疫原性，这些肽与高度免疫原性的噬菌体病毒样颗粒（VLP）平台的表面相连。尽管所有展示HPV16L2肽的VLP都引发了高滴度的抗肽抗体反应，在小鼠生殖器攻击模型中,只有一部分免疫原引发了对HPV16假病毒(PsV)感染具有强保护作用的抗体应答.这些肽中的一种，定位至HPV16L2氨基酸65-85，强烈中和HPV16PsV，但几乎没有交叉中和其他高危HPV类型的能力。为了扩大通过用这种肽接种疫苗产生的保护作用，我们用VLP免疫小鼠,所述VLP显示的肽代表来自高风险和其他HPV类型的共有序列.接种疫苗的小鼠产生广泛的抗体，对我们测试的所有HPV类型的高滴度中和活性。因此,用显示共有HPV序列的病毒样颗粒免疫是扩大针对类型特异性表位的中和抗体应答的有效方法。
