Department of Microbiology and Medical Zoology, University of Puerto Rico, Medical Sciences Campus, San Juan, Puerto Rico, USA.
School of Science and Technology, Universidad del Este, Carolina, Puerto Rico, USA.
J Immunol Res. 2019 May 22;2019:3409371. doi: 10.1155/2019/3409371. eCollection 2019.
Immunogenicity of DNA vaccines can be efficiently improved by adding adjuvants into their formulations. In this regard, the application of nano- and microparticles as vaccines adjuvants, or delivery systems, provides a powerful tool in designing modern vaccines. In the present study, we examined the role of "Supramolecular Hacky Sacks" (SHS) particles, made via the hierarchical self-assembly of a guanosine derivative, as a novel immunomodulator for DNA plasmid preparations. These plasmids code for the proteins HIV-1 Gag (pGag), the wild-type vaccinia virus Western Reserve A27 (pA27L), or a codon-optimized version of the latter (pOD1A27Lopt), which is also linked to the sequence of the outer domain-1 (OD1) from HIV-1 gp120 protein. We evaluated the enhancement of the immune responses generated by our DNA plasmid formulations in a murine model through ELISpot and ELISA assays. The SHS particles increased the frequencies of IFN--producing cells in mice independently immunized with pGag and pA27L plasmids. Moreover, the addition of SHS to pGag and pA27L DNA plasmid formulations enhanced the production of IFN- (Th1-type) over IL-4 (Th2-type) cellular immune responses. Furthermore, pGag and pA27L plasmids formulated with SHS, triggered the production of antigen-specific IgG in mice, especially the IgG2a isotype. However, no improvement of either of those adaptive immune responses was observed in mice receiving pOD1A27Lopt+SHS. Here, we demonstrated that SHS particles have the ability to improve both arms of adaptive immunity of plasmid coding "wild-type" antigens without additional strategies to boost their immunogenicity. To the best of our knowledge, this is the first report of SHS guanosine-based particles as DNA plasmid adjuvants.
DNA 疫苗的免疫原性可以通过在其配方中添加佐剂来有效提高。在这方面，纳米和微米颗粒作为疫苗佐剂或递药系统的应用，为设计现代疫苗提供了强有力的工具。在本研究中，我们研究了“超分子麻袋”（SHS）颗粒作为一种新型免疫调节剂用于 DNA 质粒制剂的作用，这些颗粒是通过鸟苷衍生物的分级自组装制成的。这些质粒编码 HIV-1 Gag（pGag）、野生型牛痘病毒西部储备 A27（pA27L）或后者的密码子优化版本（pOD1A27Lopt），后者还与 HIV-1 gp120 蛋白的外域-1（OD1）序列相连。我们通过 ELISpot 和 ELISA 测定评估了 SHS 颗粒在小鼠模型中增强我们的 DNA 质粒制剂产生的免疫应答的能力。SHS 颗粒独立地增强了用 pGag 和 pA27L 质粒免疫的小鼠中 IFN--产生细胞的频率。此外，将 SHS 添加到 pGag 和 pA27L DNA 质粒制剂中增强了 IFN-（Th1 型）而不是 IL-4（Th2 型）细胞免疫应答的产生。此外，用 SHS 配制的 pGag 和 pA27L 质粒在小鼠中触发了抗原特异性 IgG 的产生，特别是 IgG2a 同种型。然而，在用 pOD1A27Lopt+SHS 接种的小鼠中，没有观察到任何一种适应性免疫应答的改善。在这里，我们证明了 SHS 颗粒具有在没有额外策略来提高其免疫原性的情况下，改善质粒编码“野生型”抗原的适应性免疫的两个分支的能力。据我们所知，这是首次报道 SHS 基于鸟苷的颗粒作为 DNA 质粒佐剂。
