Chen D, Erickson C A, Endres R L, Periwal S B, Chu Q, Shu C, Maa Y F, Payne L G
PowderJect Vaccines Inc., 585 Science Drive, Madison, WI 53711, USA.
Vaccine. 2001 Apr 6;19(20-22):2908-17. doi: 10.1016/s0264-410x(00)00544-2.
The skin is an immunologically active site and an attractive vaccination route. All current vaccines, however, are administered either orally, intramuscularly, or subcutaneously. We previously reported that epidermal powder immunization (EPI) with an extremely small dose of powdered influenza vaccine induces protective immunity in mice. In this study, we report that commonly used adjuvants can be used in EPI to further enhance the immune responses to an antigen. The IgG antibody response to diphtheria toxoid (DT) following EPI was augmented by 25- and 250-fold, when 1 microg DT was co-delivered with aluminum phosphate (alum) and a synthetic oligonucleotide containing CpG DNA motifs (CpG DNA), respectively. These antibodies had toxin-neutralization activity and were long lasting. Furthermore, EPI using an adjuvant selectively activated different subsets of T helper cells and gave either a Th1 or a Th2 type of immune response. Similar to needle injection into deeper tissues, EPI with alum adsorbed DT promoted a predominantly IgG1 subclass antibody response and elevated level of IL-4 secreting cells. These are indicative of Th2-type immunity. In contrast, co-delivery of CpG DNA adjuvant via EPI led to Th-1 type of response as characterized by the increased production of IgG2a antibodies and IFN-gamma secreting cells. This study indicated that EPI using appropriate adjuvants can produce an augmented antibody response and desirable cellular immune responses. EPI is a promising immunization method that may be used to administer a broad range of vaccines including vaccines with adjuvants.
皮肤是一个具有免疫活性的部位，也是一种有吸引力的疫苗接种途径。然而，目前所有的疫苗都是通过口服、肌肉注射或皮下注射给药的。我们之前报道过，用极少量的粉末状流感疫苗进行表皮粉末免疫（EPI）可在小鼠中诱导保护性免疫。在本研究中，我们报告了常用的佐剂可用于EPI，以进一步增强对抗原的免疫反应。当1微克白喉类毒素（DT）分别与磷酸铝（明矾）和含有CpG DNA基序的合成寡核苷酸（CpG DNA）共同递送时，EPI后对DT的IgG抗体反应分别增强了25倍和250倍。这些抗体具有毒素中和活性且持久。此外，使用佐剂的EPI选择性地激活了不同的辅助性T细胞亚群，并产生了Th1或Th2型免疫反应。与注射到更深组织的针剂类似，用明矾吸附DT的EPI主要促进了IgG1亚类抗体反应，并提高了分泌IL-4细胞的水平。这些表明是Th2型免疫。相比之下，通过EPI共同递送CpG DNA佐剂导致了Th1型反应，其特征是IgG2a抗体和分泌IFN-γ细胞的产生增加。本研究表明，使用适当佐剂的EPI可产生增强的抗体反应和理想的细胞免疫反应。EPI是一种有前景的免疫方法，可用于接种多种疫苗，包括含佐剂的疫苗。
