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首页> 外文期刊>Vaccine >A three component mix of thioredoxin-L2 antigens elicits broadly neutralizing responses against oncogenic human papillomaviruses.
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A three component mix of thioredoxin-L2 antigens elicits broadly neutralizing responses against oncogenic human papillomaviruses.

机译：硫氧还蛋白-L2抗原的三成分混合物可引起对致癌性人乳头瘤病毒的广泛中和反应。

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摘要

Current human papillomavirus (HPV) vaccines based on major capsid protein L1 virus-like particles (VLP) provide potent type-specific protection against vaccine-type viruses (mainly HPV16 and 18), but cross-protect against only a small subset of the approximately 15 oncogenic HPV types. It is estimated that L1-VLP vaccines, which require a fairly complex production system and are still quite costly, fail to cover 20-30% of HPV cervical cancers worldwide, especially in low-resource countries. Alternative antigens relying on the N-terminal region of minor capsid protein L2 are intrinsically less immunogenic but capable of eliciting broadly neutralizing responses. We previously demonstrated the enhanced immunogenicity and cross-neutralization potential of an easily produced recombinant L2 antigen bearing the HPV16 L2(20-38) peptide epitope internally fused to bacterial thioredoxin (Trx). However, antibodies induced by Trx-HPV16 L2(20-38) failed to cross-neutralize notable high-risk HPV types such as HPV31. In the present work, the Trx-L2 design was modified to include L2 sequence information from the highly divergent HPV31 and HPV51 types in addition to HPV16, with the aim of extending cross-neutralization. Multivalent antigens comprising L2(20-38) peptides from all three HPV types on a single Trx scaffold molecule were compared to a mixture of the three type-specific monovalent Trx-L2 antigens. While multivalent antigens as well as the mixed antigens elicited similar anti-HPV16 neutralization titers, cross-reactive responses against HPV31 and HPV51 were of higher magnitude and more robust for the latter formulation. A mixture of monovalent Trx-L2 antigens thus represents a candidate lead for the development of a broadly cross-protective, low-cost second-generation anti-HPV vaccine.
机译：当前的基于主要衣壳蛋白L1病毒样颗粒（VLP）的人乳头瘤病毒（HPV）疫苗可针对疫苗型病毒（主要是HPV16和18）提供有效的类型特异性保护，但仅可针对约一小部分的交叉保护15种致癌性HPV。据估计，L1-VLP疫苗需要相当复杂的生产系统，而且仍然很昂贵，无法覆盖全世界的20-30％的HPV宫颈癌，尤其是在资源贫乏的国家。依赖于较小衣壳蛋白L2 N末端区域的替代抗原本质上免疫原性较低，但能够引发广泛的中和反应。我们以前证明了带有内部融合到细菌硫氧还蛋白（Trx）的HPV16 L2（20-38）肽表位的易于生产的重组L2抗原的增强的免疫原性和交叉中和潜力。但是，Trx-HPV16 L2（20-38）诱导的抗体无法交叉中和著名的高风险HPV类型，例如HPV31。在当前工作中，Trx-L2设计经过修改，除了HPV16外，还包括来自高度不同的HPV31和HPV51类型的L2序列信息，目的是扩展交叉中和作用。将包含来自单个Trx支架分子上所有三种HPV类型的L2（20-38）肽的多价抗原与三种类型特异性单价Trx-L2抗原的混合物进行比较。尽管多价抗原和混合抗原引起相似的抗HPV16中和效价，但针对HPV31和HPV51的交叉反应反应强度更高，对于后一种制剂更强。因此，单价Trx-L2抗原的混合物代表了广泛交叉保护，低成本第二代抗HPV疫苗开发的候选先导。

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