Department of Chemical and Biomolecular Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea.
J Control Release. 2013 Dec 10;172(2):579-88. doi: 10.1016/j.jconrel.2013.04.016. Epub 2013 Apr 30.
The need for annual revaccination against influenza is a burden on the healthcare system, leads to low vaccination rates and makes timely vaccination difficult against pandemic strains, such as during the 2009 H1N1 influenza pandemic. In an effort toward achieving a broadly protective vaccine that provides cross-protection against multiple strains of influenza, this study developed a microneedle patch to co-immunize with A/PR8 influenza hemagglutinin DNA and A/PR8 inactivated virus vaccine. We hypothesize that this dual component vaccination strategy administered to the skin using microneedles will provide cross-protection against other strains of influenza. To test this hypothesis, we developed a novel coating formulation that did not require additional excipients to increase coating solution viscosity by using the DNA vaccine itself to increase viscosity and thereby enable thick coatings of DNA vaccine and inactivated virus vaccine on metal microneedles. Co-immunization in this way not only generated robust antibody responses against A/PR8 influenza but also generated robust heterologous antibody responses against pandemic 2009 H1N1 influenza in mice. Challenge studies showed complete cross-protection against lethal challenge with live pandemic 2009 H1N1 virus. Control experiments using A/PR8 inactivated influenza virus vaccine with placebo DNA coated onto microneedles produced lower antibody titers and provided incomplete protection against challenge. Overall, this is the first study showing DNA solution as a microneedle coating agent and demonstrating cross-protection by co-immunization with inactivated virus and DNA vaccine using coated microneedles.
每年接种流感疫苗的需求给医疗保健系统带来了负担，导致接种率低，并且难以针对大流行株（如 2009 年 H1N1 流感大流行期间）及时接种疫苗。为了开发一种广泛保护的疫苗，提供针对多种流感株的交叉保护，本研究开发了一种微针贴片，用于与 A/PR8 流感血凝素 DNA 和 A/PR8 灭活病毒疫苗共同免疫。我们假设，使用微针将这种双组分疫苗接种策略施用于皮肤，将提供针对其他流感株的交叉保护。为了验证这一假设，我们开发了一种新型涂层配方，该配方不需要额外的赋形剂来增加涂层溶液的粘度，而是使用 DNA 疫苗本身来增加粘度，从而能够在金属微针上涂覆厚厚的 DNA 疫苗和灭活病毒疫苗。以这种方式进行共同免疫不仅产生了针对 A/PR8 流感的强大抗体反应，还产生了针对大流行 2009 年 H1N1 流感的强大异源抗体反应。攻毒研究表明，对活的大流行 2009 年 H1N1 病毒的致死性攻毒具有完全的交叉保护作用。使用涂有微针的安慰剂 DNA 包被的 A/PR8 灭活流感病毒疫苗进行的对照实验产生的抗体滴度较低，并且对攻毒的保护不完全。总的来说，这是第一项表明 DNA 溶液可用作微针涂层剂，并通过使用涂层微针进行灭活病毒和 DNA 疫苗的共同免疫来证明交叉保护的研究。
