PDF(Pubmed)
Abstract：
Epstein-Barr virus (EBV) infects more than 95% of adults worldwide and is closely associated with various malignancies. Considering the complex life cycle of EBV, developing vaccines targeting key entry glycoproteins to elicit robust and durable adaptive immune responses may provide better protection. EBV gHgL-, gB- and gp42-specific antibodies in healthy EBV carriers contributed to sera neutralizing abilities in vitro, indicating that they are potential antigen candidates. To enhance the immunogenicity of these antigens, we formulate three nanovaccines by co-delivering molecular adjuvants (CpG and MPLA) and antigens (gHgL, gB or gp42). These nanovaccines induce robust humoral and cellular responses through efficient activation of dendritic cells and germinal center response. Importantly, these nanovaccines generate high levels of neutralizing antibodies recognizing vulnerable sites of all three antigens. IgGs induced by a cocktail vaccine containing three nanovaccines confer superior protection from lethal EBV challenge in female humanized mice compared to IgG elicited by individual NP-gHgL, NP-gB and NP-gp42. Importantly, serum antibodies elicited by cocktail nanovaccine immunization confer durable protection against EBV-associated lymphoma. Overall, the cocktail nanovaccine shows robust immunogenicity and is a promising candidate for further clinical trials.
摘要：
EB病毒（EBV）感染全球95％以上的成年人，并与各种恶性肿瘤密切相关。考虑到EBV复杂的生命周期，开发针对关键进入糖蛋白的疫苗，以引发强大而持久的适应性免疫反应，可能会提供更好的保护。EBVgHgL-,健康EBV携带者的gB和gp42特异性抗体有助于体外血清中和能力，表明它们是潜在的候选抗原。为了增强这些抗原的免疫原性，我们通过共同递送分子佐剂(CpG和MPLA)和抗原(gHgL，gB或gp42)。这些纳米疫苗通过树突状细胞的有效活化和生发中心反应诱导强烈的体液和细胞反应。重要的是,这些纳米疫苗会产生高水平的中和抗体，识别所有三种抗原的脆弱位点。与单个NP-gHgL引发的IgG相比，含有三种纳米疫苗的鸡尾酒疫苗诱导的IgG对雌性人源化小鼠的致死性EBV攻击具有更好的保护作用。NP-gB和NP-gp42。重要的是,鸡尾酒纳米疫苗免疫产生的血清抗体赋予对EBV相关淋巴瘤的持久保护。总的来说,鸡尾酒纳米疫苗显示出强大的免疫原性，是进一步临床试验的有希望的候选药物。
