Department of Infectious Disease and Global Health, Tufts University Cummings School of Veterinary Medicine, 200 Westboro Road, North Grafton, MA 01536, USA.
Department of Microbiology and Molecular Genetics, Oklahoma State University, 307 Life Sciences East, Stillwater, OK 74075, USA.
Microbes Infect. 2014 Sep;16(9):796-803. doi: 10.1016/j.micinf.2014.07.013. Epub 2014 Aug 8.
A key consideration to produce a successful vaccine is the choice of appropriate vaccination route. Though most vaccines are administered parenterally, this route is not effective in producing a robust mucosal or cell-mediated response. Intradermal and sublingual vaccinations have been explored recently as potential needle-free immunization strategies. We explored intradermal and sublingual routes as well as the combination of the two routes in eliciting both systemic and mucosal immune responses. Mice were immunized intradermally or sublingually with dmLT, a mutant of Escherichia coli heat-labile toxin. A systemic IgG response is dominant in intradermal immunization while a mucosal IgA response is dominant in sublingual immunization. When routes were combined, a synergistic response was seen with high titers of anti-dmLT IgG and IgA. IpaB/IpaD antigens of Shigella flexneri type III secretion system, were admixed with dmLT as adjuvant and administered by each route alone or in combination. Again, the intradermal route elicited a systemic response while the sublingual route elicited a mucosal response. When combined, the routes produced a robust synergistic response to both antigens that exhibited a balanced Th1/Th2 response. These results provide a new potential needle-free immunization strategy that will benefit low income countries and increase compliance in industrial countries.
生产成功疫苗的一个关键考虑因素是选择适当的接种途径。尽管大多数疫苗都是通过注射给药,但这种途径不能有效地产生强大的粘膜或细胞介导的反应。最近,人们探索了皮内和舌下接种作为潜在的无针免疫接种策略。我们探索了皮内和舌下途径以及两种途径的联合应用,以引发全身和粘膜免疫反应。用大肠杆菌不耐热毒素(dmLT)的突变体通过皮内或舌下途径免疫小鼠。皮内免疫以产生全身性 IgG 反应为主,而舌下免疫以产生粘膜性 IgA 反应为主。当途径联合使用时,会产生针对 dmLT 的 IgG 和 IgA 的高滴度协同反应。志贺氏菌 III 型分泌系统的 IpaB/IpaD 抗原与 dmLT 混合作为佐剂,单独或联合通过每种途径给药。同样,皮内途径引起全身反应,而舌下途径引起粘膜反应。当联合使用时,两种途径对两种抗原都产生了强大的协同反应,表现出平衡的 Th1/Th2 反应。这些结果提供了一种新的潜在的无针免疫接种策略,将使低收入国家受益,并提高工业国家的依从性。