Stabilization of Influenza Vaccine Enhances Protection by Microneedle Delivery in the Mouse Skin
Stabilization of Influenza Vaccine Enhances Protection by Microneedle Delivery in the Mouse Skin
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DOI：
10.1371/journal.pone.0007152
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发表时间：
2009-09-25
期刊：
影响因子：
3.7
通讯作者：
Kang, Sang-Moo
中科院分区：
文献类型：
--
作者：
Quan, Fu-Shi;Kim, Yeu-Chun;Kang, Sang-Moo
背景：简单有效的疫苗接种对于每年推荐的流感疫苗接种尤为重要。我们假设，使用含有疫苗涂层的微针的贴片将疫苗递送到皮肤可能是一种有吸引力的方法，以提高流感疫苗接种的依从性和effictiveness.Methodology/Principal Findings：用灭活流感疫苗涂层的固体微针阵列制备简单的疫苗递送到皮肤。然而，流感疫苗的稳定性，如通过血凝活性所测量的，被发现在微针涂覆期间被显著破坏。向微针涂层制剂中添加海藻糖保留了血凝活性，表明涂层流感疫苗的稳定性。对于肌内和微针皮肤免疫，未稳定化疫苗的递送产生较弱的保护性免疫应答，包括病毒中和抗体、保护效力和对流感病毒的回忆免疫应答。与稳定疫苗相比，使用不稳定疫苗的免疫也改变了抗体同种型的模式。重要的是，一个单一的微针为基础的疫苗接种，使用稳定的流感疫苗被发现是上级肌内免疫，在控制病毒复制，以及在诱导快速召回免疫反应后challenge.Conclusions/Significance：血凝素的功能完整性与诱导提高对流感的保护性免疫。与常规肌肉内免疫相比，皮肤中的简单微针流感疫苗接种产生了上级保护。这种方法可能也适用于其他疫苗。
Background: Simple and effective vaccine administration is particularly important for annually recommended influenza vaccination. We hypothesized that vaccine delivery to the skin using a patch containing vaccine-coated microneedles could be an attractive approach to improve influenza vaccination compliance and efficacy.Methodology/Principal Findings: Solid microneedle arrays coated with inactivated influenza vaccine were prepared for simple vaccine delivery to the skin. However, the stability of the influenza vaccine, as measured by hemagglutination activity, was found to be significantly damaged during microneedle coating. The addition of trehalose to the microneedle coating formulation retained hemagglutination activity, indicating stabilization of the coated influenza vaccine. For both intramuscular and microneedle skin immunization, delivery of un-stabilized vaccine yielded weaker protective immune responses including viral neutralizing antibodies, protective efficacies, and recall immune responses to influenza virus. Immunization using un-stabilized vaccine also shifted the pattern of antibody isotypes compared to the stabilized vaccine. Importantly, a single microneedle-based vaccination using stabilized influenza vaccine was found to be superior to intramuscular immunization in controlling virus replication as well as in inducing rapid recall immune responses post challenge.Conclusions/Significance: The functional integrity of hemagglutinin is associated with inducing improved protective immunity against influenza. Simple microneedle influenza vaccination in the skin produced superior protection compared to conventional intramuscular immunization. This approach is likely to be applicable to other vaccines too.