Snook Joshua D, Chesson Charles B, Peniche Alex G, Dann Sara M, Paulucci Adriana, Pinchuk Iryna V, Rudra Jai S
Department of Pharmacology & Toxicology, University of Texas Medical Branch, Galveston, TX 77555, USA.
J Mater Chem B. 2016 Mar 7;4(9):1640-1649. doi: 10.1039/c5tb01623a. Epub 2015 Oct 29.
To combat mucosal pathogens that cause gastrointestinal (GI) infections, local mucosal immunity is required which is best achieved through oral vaccination. Oral delivery of vaccines is also a safe and convenient alternative to injected vaccines due to its non-invasive nature and high compliance rate for all ages. However, the lack of effective and safe mucosal adjuvants, the selective permeability of the mucus barrier, and the harsh GI environment continue to pose a significant challenge for oral vaccine development. Microparticle-based strategies are attractive for oral vaccination due to their ability to efficiently penetrate the mucus barrier and have the added advantage of protecting the antigen in the harsh gastric environment. In this work, self-adjuvanting peptide nanofiber-CaCO composite microparticles were prepared and investigated for oral vaccine delivery. Compared to polymeric microparticles, inorganic CaCO microparticles have unique advantages due to the biocompatibility of CaCO as a natural mineral, mild preparation conditions, and its porous structure that is suitable for loading other materials. Particle size distribution, nanofiber loading efficiency, morphology, and degradation in simulated gastric fluid were characterized. The composite microparticles were efficient at penetrating the mucus barrier and were localized to immune inductive sites and elicited the production of mucosal antibody responses, particularly the protective IgA isotype following oral administration. The magnitude of the mucosal immune response was comparable to the gold-standard adjuvant cholera toxin B (CTB). Our results indicate that OVA-KFE8/CaCO composite microparticles are efficient self-adjuvanting oral vaccine delivery vehicles for induction of mucosal antibody responses.
为对抗引起胃肠道（GI）感染的黏膜病原体，需要局部黏膜免疫，而通过口服疫苗能最好地实现这一点。由于其非侵入性以及各年龄段的高依从率，口服疫苗也是注射疫苗的一种安全且便捷的替代方式。然而，缺乏有效且安全的黏膜佐剂、黏液屏障的选择性通透性以及恶劣的胃肠道环境，仍然是口服疫苗开发面临的重大挑战。基于微粒的策略对口服疫苗接种具有吸引力，因为它们能够有效穿透黏液屏障，并且在恶劣的胃环境中具有保护抗原的额外优势。在这项工作中，制备了自佐剂肽纳米纤维 - 碳酸钙（CaCO）复合微粒，并对其用于口服疫苗递送进行了研究。与聚合物微粒相比，无机碳酸钙微粒具有独特优势，因为碳酸钙作为天然矿物质具有生物相容性、制备条件温和，且其多孔结构适合负载其他材料。对粒径分布、纳米纤维负载效率、形态以及在模拟胃液中的降解情况进行了表征。复合微粒能够有效穿透黏液屏障，并定位于免疫诱导部位，口服给药后能引发黏膜抗体反应的产生，特别是保护性IgA同种型。黏膜免疫反应的强度与金标准佐剂霍乱毒素B（CTB）相当。我们的结果表明，OVA - KFE8/CaCO复合微粒是用于诱导黏膜抗体反应的高效自佐剂口服疫苗递送载体。
