Hu He, Steinmetz Nicole F
Department of NanoEngineering, University of California San Diego, 9500 Gilman Dr., La Jolla, CA 92039, USA.
Department of Bioengineering, University of California San Diego, 9500 Gilman Dr., La Jolla, CA 92039, USA.
Cancers (Basel). 2021 Jun 10;13(12):2909. doi: 10.3390/cancers13122909.
To develop a human epidermal growth factor receptor-2 (HER2)-specific cancer vaccine, using a plant virus-like particle (VLP) platform. Copper-free click chemistry and infusion encapsulation protocols were developed to prepare VLPs displaying the HER2-derived CH401 peptide epitope, with and without Toll-like receptor 9 (TLR9) agonists loaded into the interior cavity of the VLPs; Physalis mottle virus (PhMV)-based VLPs were used. After prime-boost immunization of BALB/c mice through subcutaneous administration of the vaccine candidates, sera were collected and analyzed by enzyme-linked immunosorbent assay (ELISA) for the CH401-specific antibodies; Th1 vs. Th2 bias was determined by antibody subtyping and splenocyte assay. Efficacy was assessed by tumor challenge using DDHER2 tumor cells. We successful developed two VLP-based anti-HER2 vaccine candidates-PhMV-CH401 vs. CpG-PhMV-CH401; however, the addition of the CpG adjuvant did not confer additional immune priming. Both VLP-based vaccine candidates elicited a strong immune response, including high titers of HER2-specific immunoglobulins and increased toxicity of antisera to DDHER2 tumor cells. DDHER2 tumor growth was delayed, leading to prolonged survival of the vaccinated vs. naïve BALB/C mice. The PhMV-based anti-HER2 vaccine PhMV-CH401, demonstrated efficacy as an anti-HER2 cancer vaccine. Our studies highlight that VLPs derived from PhMV are a promising platform to develop cancer vaccines.
利用植物病毒样颗粒（VLP）平台开发一种人表皮生长因子受体2（HER2）特异性癌症疫苗。开发了无铜点击化学和注入封装方案，以制备展示HER2衍生的CH401肽表位的VLP，VLP的内腔中分别装载和不装载Toll样受体9（TLR9）激动剂；使用基于酸浆斑驳病毒（PhMV）的VLP。通过皮下注射候选疫苗对BALB/c小鼠进行初免-加强免疫后，收集血清并通过酶联免疫吸附测定（ELISA）分析CH401特异性抗体；通过抗体亚型分析和脾细胞测定确定Th1与Th2偏向。使用DDHER2肿瘤细胞进行肿瘤攻击评估疗效。我们成功开发了两种基于VLP的抗HER2候选疫苗——PhMV-CH401与CpG-PhMV-CH401；然而，添加CpG佐剂并未带来额外的免疫激发。两种基于VLP的候选疫苗均引发了强烈的免疫反应，包括高滴度的HER2特异性免疫球蛋白以及抗血清对DDHER2肿瘤细胞毒性的增加。DDHER2肿瘤生长延迟，导致接种疫苗的BALB/C小鼠比未接种的小鼠存活时间延长。基于PhMV的抗HER2疫苗PhMV-CH401证明了其作为抗HER2癌症疫苗的疗效。我们的研究强调，源自PhMV的VLP是开发癌症疫苗的一个有前景的平台。
