Grenfell Rafaella F Q, Shollenberger Lisa M, Samli E Farah, Harn Donald A
Department of Infectious Diseases, College of Veterinary Medicine, and The Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, Georgia, USA Schistosomiasis Laboratory, Rene Rachou Research Center, Oswaldo Cruz Foundation, Belo Horizonte, Minas Gerais, Brazil.
Department of Infectious Diseases, College of Veterinary Medicine, and The Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, Georgia, USA.
Clin Vaccine Immunol. 2015 Mar;22(3):336-43. doi: 10.1128/CVI.00714-14. Epub 2015 Jan 21.
Vaccination remains the most effective public health tool to prevent infectious diseases. Many vaccines are marginally effective and need enhancement for immunocompromised, elderly, and very young populations. To enhance immunogenicity, we exploited the biphasic property of the (RADA)4 synthetic oligopeptide to create VacSIM (vaccine self-assembling immune matrix), a new delivery method. VacSIM solution can easily be mixed with antigens, organisms, and adjuvants for injection. Postinjection, the peptides self-assemble into hydrated nanofiber gel matrices, forming a depot with antigens and adjuvants in the aqueous phase. We believe the depot provides slow release of immunogens, leading to increased activation of antigen-presenting cells that then drive enhanced immunogenicity. Using recombinant hepatitis B virus surface antigen (rHBsAg) as a model immunogen, we compared VacSIM delivery to delivery in alum or complete Freund's adjuvant (CFA). Delivery of the rHBsAg antigen to mice via VacSIM without adjuvant elicited higher specific IgG responses than when rHBsAg was delivered in alum or CFA. Evaluating IgG subtypes showed a mixed Th1/Th2 type response following immunization with VacSIM, which was driven further toward Th1 with addition of CpG as the adjuvant. Increased specific IgG endpoint titers were observed in both C57BL/6 and BALB/c mice, representative of Th1 and Th2 environments, respectively. Restimulation of splenocytes suggests that VacSIM does not cause an immediate proinflammatory response in the host. Overall, these results suggest that VacSIM, as a new delivery method, has the potential to enhance immunogenicity and efficacy of numerous vaccines.
疫苗接种仍然是预防传染病最有效的公共卫生工具。许多疫苗效果有限，需要针对免疫功能低下者、老年人和非常年幼的人群进行改进。为了增强免疫原性，我们利用（RADA）4合成寡肽的双相特性创建了VacSIM（疫苗自组装免疫基质），这是一种新的递送方法。VacSIM溶液可轻松与抗原、生物体和佐剂混合用于注射。注射后，肽自组装成水合纳米纤维凝胶基质，在水相中形成含有抗原和佐剂的储存库。我们认为该储存库可使免疫原缓慢释放，从而导致抗原呈递细胞的激活增加，进而增强免疫原性。使用重组乙肝病毒表面抗原（rHBsAg）作为模型免疫原，我们将VacSIM递送与明矾或完全弗氏佐剂（CFA）递送进行了比较。通过无佐剂的VacSIM将rHBsAg抗原递送至小鼠，比在明矾或CFA中递送rHBsAg时引发更高的特异性IgG反应。评估IgG亚型显示，用VacSIM免疫后出现混合的Th1/Th2型反应，添加CpG作为佐剂后反应进一步偏向Th1。在分别代表Th1和Th2环境的C57BL/6和BALB/c小鼠中均观察到特异性IgG终点滴度增加。脾细胞的再刺激表明VacSIM不会在宿主中引起立即的促炎反应。总体而言，这些结果表明，VacSIM作为一种新的递送方法，有可能增强多种疫苗的免疫原性和效力。
