Coucke D, Schotsaert M, Libert C, Pringels E, Vervaet C, Foreman P, Saelens X, Remon J P
Laboratory of Pharmaceutical Technology, Ghent University, Ghent, Belgium.
Vaccine. 2009 Feb 18;27(8):1279-86. doi: 10.1016/j.vaccine.2008.12.013. Epub 2008 Dec 27.
Mucosal vaccination has several advantages over parenteral vaccination. In this study, viscosity-enhancing mucosal delivery systems for the induction of an adaptive immune response against viral antigen were investigated. Powder formulations based on spray-dried mixtures of starch (Amioca)/poly(acrylic acid) (Carbopol 974P) in different ratios were used as carriers of the viral antigen. A comparison of these formulations for intranasal delivery of heat-inactivated influenza virus combined with LTR192G adjuvant was made in vivo in a rabbit model. Individual rabbit sera were tested for seroconversion against hemagglutinin (HA), the major surface antigen of influenza. The powder vaccine formulations were able to induce systemic anti-HA IgG responses. The presence of Carbopol 974P improved the kinetics of the immune responses and the level of IgG titers in a dose-dependent way which was correlated with moderately irritating capacities of the formulation. In contrast, mucosal IgA responses were not detected. In conclusion, it was demonstrated that the use of bioadhesive carriers based on Amioca starch and poly(acrylic acid) facilitates the induction of a systemic anti-HA antibody response after intranasal vaccination with a whole virus influenza vaccine.
黏膜疫苗接种相对于肠胃外疫苗接种具有若干优势。在本研究中,对用于诱导针对病毒抗原的适应性免疫反应的增黏黏膜递送系统进行了研究。基于不同比例的淀粉(木薯淀粉)/聚丙烯酸(卡波姆974P)喷雾干燥混合物的粉末制剂被用作病毒抗原的载体。在兔模型中对这些制剂与LTR192G佐剂联合用于鼻内递送热灭活流感病毒进行了体内比较。检测了各只兔子血清针对流感主要表面抗原血凝素(HA)的血清转化情况。粉末疫苗制剂能够诱导全身性抗HA IgG反应。卡波姆974P的存在以剂量依赖方式改善了免疫反应动力学和IgG滴度水平,这与制剂的中等刺激能力相关。相比之下,未检测到黏膜IgA反应。总之,结果表明,使用基于木薯淀粉和聚丙烯酸的生物黏附载体有助于在用全病毒流感疫苗进行鼻内接种后诱导全身性抗HA抗体反应。