论文标题：A proof-of-concept study for the design of a VLP-based combinatorial HPV and placental malaria vaccine

期刊：

作者：Christoph M. Janitzek, Julianne Peabody, Susan Thrane, Philip H. R. Carlsen, Thor G. Theander, Ali Salanti, Bryce Chackerian, Morten A. Nielsen, Adam F. Sander

发表时间：2019/03/27

数字识别码： 10.1038/s41598-019-41522-5

原文链接：

在非洲，宫颈癌和胎盘疟疾（placental malaria, PM）是非常严重的公共卫生问题。目前尚无可用的PM疫苗，而市售的人乳头瘤病毒（HPV）疫苗价格也十分昂贵。而在撒哈拉以南的非洲地区，有许多需要同时接种两种疫苗的青少年女性，因此研发HPV和PM联合疫苗这一想法显然很具有吸引力。

来自丹麦哥本哈根大学的研究者Adam F. Sander等开展了一项概念验证研究，他们利用了衍生自AP205衣壳蛋白的病毒样颗粒（VLP）来开发联合疫苗，经设计可同时表达出两种临床相关抗原（HPV RG1表位和VAR2CSA PM抗原）。研究者共开发了三种不同的联合VLP，它们分别显示出一个、两个以及五个串联的RG1表位，三种情况下VLP的形成能力均不受影响。通过脱落蛋白标签/捕获器（Tag/Catcher）相互作用，在不影响疫苗稳定性的情况下研究者实现了VAR2CSA的共表达。接种该联合疫苗能够降低体内HPV感染风险，并诱导产生抗VAR2CSA IgG抗体，该抗体在体外结合抑制试验中能够抑制被感染红细胞上表达的天然VAR2CSA与硫酸软骨素A之间的结合。这些结果表明，利用Tag/Catcher AP205 VLP系统制备出能够诱导具有双重特异性抗体的联合疫苗是有可行性的。

图1：HPV和PM VLP联合疫苗设计示意图

摘要：In Africa, cervical cancer and placental malaria (PM) are a major public health concern. There is currently no available PM vaccine and the marketed Human Papillomavirus (HPV) vaccines are prohibitively expensive. The idea of a combinatorial HPV and PM vaccine is attractive because the target population for vaccination against both diseases, adolescent girls, would be overlapping in Sub-Saharan Africa. Here we demonstrate proof-of-concept for a combinatorial vaccine utilizing the AP205 capsid-based virus-like particle (VLP) designed to simultaneously display two clinically relevant antigens (the HPV RG1 epitope and the VAR2CSA PM antigen). Three distinct combinatorial VLPs were produced displaying one, two or five concatenated RG1 epitopes without obstructing the VLP’s capacity to form. Co-display of VAR2CSA was achieved through a split-protein Tag/Catcher interaction without hampering the vaccine stability. Vaccination with the combinatorial vaccine(s) was able to reduce HPV infection in vivo and induce anti-VAR2CSA IgG antibodies, which inhibited binding between native VAR2CSA expressed on infected red blood cells and chondroitin sulfate A in an in vitro binding-inhibition assay. These results show that the Tag/Catcher AP205 VLP system can be exploited to make a combinatorial vaccine capable of eliciting antibodies with dual specificity.

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