Jenika Devi, Pounraj Saranya, Wibowo David, Flaxl Leonhard M, Rehm Bernd H A, Mintern Justine D
Department of Biochemistry and Pharmacology, The University of Melbourne, Bio21 Molecular Science and Biotechnology Institute, Parkville, VIC, 3010, Australia.
Centre for Cell Factories and Biopolymers, Griffith Institute for Drug Discovery, Griffith University, Nathan, QLD, 4111, Australia.
NPJ Vaccines. 2024 Jan 23;9(1):18. doi: 10.1038/s41541-023-00787-8.
There is an unmet need for antigen delivery systems that elicit efficient T cell priming to prevent infectious diseases or for treatment of cancers. Here, we explored the immunogenic potential of biologically assembled biopolymer particles (BPs) that have been bioengineered to display the antigenic MHC I and MHC II epitopes of model antigen ovalbumin (OVA). Purified dendritic cells (DCs) captured BP-OVA and presented the associated antigenic epitopes to CD4 T cells and CD8 T cells. Vaccination with BP-OVA in the absence of adjuvant elicited antigen presentation to OVA-specific CD8 and CD4 T cells and cross-primed effective cytotoxic T lymphocyte (CTL) killers. BP-OVA induction of CTL killing did not require CD4 T cell help, with active CTLs generated in BP-OVA vaccinated I-A and CD40 mice. In contrast, IL-15 and type I IFN were required, with abrogated CTL activity in vaccinated IL-15 and IFNAR1 mice. cDC1 and/or CD103 DCs were not essential for BP-OVA specific CTL with immunization eliciting responses in Batf3 mice. Poly I:C, but not LPS or CpG, co-administered as an adjuvant with BP-OVA boosted CTL responses. Finally, vaccination with BP-OVA protected against B16-OVA melanoma and Eμ-myc-GFP-OVA lymphoma inoculation. In summary, we have demonstrated that epitope-displaying BPs represent an antigen delivery platform exhibiting a unique mechanism to effectively engage T cell immune responses.
对于能够引发高效T细胞启动以预防传染病或用于癌症治疗的抗原递送系统，仍存在未满足的需求。在此，我们探索了生物组装的生物聚合物颗粒（BP）的免疫原性潜力，这些颗粒已通过生物工程改造以展示模型抗原卵清蛋白（OVA）的抗原性MHC I和MHC II表位。纯化的树突状细胞（DC）捕获BP-OVA，并将相关的抗原表位呈递给CD4 T细胞和CD8 T细胞。在没有佐剂的情况下用BP-OVA进行疫苗接种可引发对OVA特异性CD8和CD4 T细胞的抗原呈递，并交叉启动有效的细胞毒性T淋巴细胞（CTL）杀伤作用。BP-OVA诱导的CTL杀伤作用不需要CD4 T细胞的帮助，在接种BP-OVA的I-A和CD40小鼠中可产生活性CTL。相比之下，IL-15和I型干扰素是必需的，在接种疫苗的IL-15和IFNAR1小鼠中CTL活性被消除。cDC1和/或CD103 DC对于BP-OVA特异性CTL不是必需的，免疫接种在Batf3小鼠中引发反应。与BP-OVA共同作为佐剂给药的聚肌胞苷酸（Poly I:C），而不是LPS或CpG，可增强CTL反应。最后，用BP-OVA进行疫苗接种可预防B16-OVA黑色素瘤和Eμ-myc-GFP-OVA淋巴瘤接种。总之，我们已经证明，展示表位的BP代表了一种抗原递送平台，其具有独特的机制来有效参与T细胞免疫反应。
