Development of a Modular NTA:His Tag Viral Vaccine for Co-delivery of Antigen and Adjuvant
Development of a Modular NTA:His Tag Viral Vaccine for Co-delivery of Antigen and Adjuvant
复制标题
DOI：
10.1021/acs.bioconjchem.2c00601
复制
发表时间：
2023-01-06
影响因子：
4.7
通讯作者：
Steinmetz, Nicole F.
中科院分区：
文献类型：
--
作者：
Chung, Young Hun;Volckaert, Britney A.;Steinmetz, Nicole F.
SARS-CoV-2大流行突出了对有效但快速生产的疫苗的需求。值得注意的是，具有将抗原和佐剂共同递送至同一细胞的即插即用能力的疫苗已经显示出显著的成功。我们利用氮基三乙酸（NTA）组氨酸（His）-标签化学与病毒佐剂的方法结合了这两个特征：即插即用和共递送。我们专门利用豇豆花叶病毒（CPMV）和噬菌体Q β的病毒样颗粒作为佐剂，并结合模型抗原卵清蛋白（OVA）。通过SDS-PAGE、蛋白质印迹和ELISA验证抗原与佐剂/载体的成功结合。在C57 BL/6 J小鼠中的免疫证明，使用Q β-而不是CPMV -，使用Q β-NiNTA：His-OVA相对于抗原和佐剂的简单混合物，存在针对靶抗原的改善的抗体应答。抗体同种型也显示疫苗的配制可改变辅助性T细胞偏好;而Q β-NiNTA：His-OVA颗粒产生平衡的Th 1/Th 2偏好，混合物是强烈的Th 2。在B16 F10-OVA的小鼠模型中，我们进一步证明了与对照组相比，疫苗组的存活率提高，肿瘤生长减慢。NiNTA：他的化学研究显示了快速开发下一代疫苗的潜力，使其具有即插即用的能力，并通过共同递送到同一细胞来提高有效性。
The SARS-CoV-2 pandemic has highlighted the need for vaccines that are effective, but quickly produced. Of note, vaccines with plug-and-play capabilities that co -deliver antigen and adjuvant to the same cell have shown remarkable success. Our approach of utilizing a nitrilotriacetic acid (NTA) histidine (His)-tag chemistry with viral adjuvants incorporates both of these characteristics: plug-and-play and co-delivery. We specifically utilize the cowpea mosaic virus (CPMV) and the virus-like particles from bacteriophage Q beta as adjuvants and bind the model antigen ovalbumin (OVA). Successful binding of the antigen to the adjuvant/carrier was verified by SDS-PAGE, western blot, and ELISA. Immunization in C57BL/6J mice demonstrates that with Q beta -but not CPMV -there is an improved antibody response against the target antigen using the Q beta-NiNTA:His-OVA versus a simple admixture of antigen and adjuvant. Antibody isotyping also shows that formulation of the vaccines can alter T helper biases; while the Q beta-NiNTA:His-OVA particle produces a balanced Th1/Th2 bias the admixture was strongly Th2. In a mouse model of B16F10-OVA, we further demonstrate improved survival and slower tumor growth in the vaccine groups compared to controls. The NiNTA:His chemistry demonstrates potential for rapid development of future generation vaccines enabling plug-and-play capabilities with effectiveness boosted by co-delivery to the same cell.