Development of small near-infrared laser system capable of improving immune respo

描述（由申请人提供）：本项目的广泛和长期目标是在不使用化学或生物佐剂的情况下增强疫苗的有效性。我们将通过证明小型激光装置增强皮内接种反应的可行性来解决这一目标。一些研究人员已经表明，一种有希望的使疫苗更好地发挥作用的新方法是通过短暂暴露于无害的激光来治疗皮肤，然后在该皮肤部位引入疫苗。这种方法可以在不需要化学佐剂的情况下产生更好的疫苗应答。到目前为止，这些响应都是使用大型且相对昂贵的台式设备产生的。 最近，低功率近红外（NIR）激光也被证明可以显著增强疫苗反应。这将使使用小型、低成本的近红外激光系统来增强疫苗成为可能，这在临床环境中是实用的。目前还没有设计用于提供疫苗增强治疗的这种便携式设备。因此，本项目的目标是：1）完成原型手持式激光器，该激光器可以复制较大激光系统的光束参数，该激光系统已显示出诱导对皮内疫苗的免疫应答显著增强的能力，以及2）证明这种小型激光器可以在已建立的小鼠疫苗接种模型中产生与较大激光器等效的免疫应答。这个项目，如果成功，将打开大门，更大的测试， 激光为基础的佐剂与各种疫苗，并将形成基础的临床准备设备的发展。 对于这个项目，一套原型手持设备将使用现有的手持激光设计。一个装置将使用1064 nm二极管，另一个装置将使用1300 nm二极管（1300 nm装置将用作阴性对照系统）。这些装置将使用标准制造工艺制造，并进行台架测试，以显示其发射曲线与已描述的增强疫苗反应的发射曲线相似。 一旦这些原型被建造并进行实验室测试，它们将与已经被证明可以增强疫苗反应的更大的激光系统一起进行测试。使用已建立的小鼠疫苗模型，将首先测试小型激光系统，以显示治疗剂量对皮肤无害且无损伤。在此之后，将测试它们对流感疫苗接种产生等效免疫应答的能力，包括对流感致命挑战的保护。

DESCRIPTION (provided by applicant): The broad and long-term objective of this project is to amplify the effectiveness of vaccines without the use of chemical or biological adjuvants. We will address this objective by demonstrating the feasibility for small laser- based devices to enhance responses to intradermal vaccination. A number of investigators have shown that a promising new way to make vaccines work better is to treat the skin with a brief exposure to a non-harmful laser light and then introduce the vaccine at that skin site. This approach can result in better vaccine responses without the need for chemical adjuvants. Until now, these responses have been generated using large and relatively expensive bench top devices. Recently, low-power, near-infrared (NIR) laser light has also been shown to significantly enhancing vaccine responses. This would make it possible to use small, low-cost NIR laser systems to enhance vaccines that would be practical in the clinical setting. There are currently no such portable devices designed to deliver vaccine-enhancing treatments. Therefore, the objectives of this project are 1) to complete a prototype handheld laser that can replicate the beam parameters of a larger laser system that has shown the ability to induce significant enhancement of immune responses to intradermal vaccines, and 2) to demonstrate that this small laser can produce equivalent immune responses to the larger laser in an established mouse vaccination model. This project, if successful, will open the door for greater testing of the laser based adjuvant with a variety of vaccines, and will form the foundation for development of clinical-ready devices. For this project, a set of prototype handheld device will be created using an existing handheld laser design. One device will use a 1064 nm diode and the other a 1300 nm diode (the 1300 nm device will serve as a negative control system). These devices will be built using standard fabrication processes and bench tested to show their emission profile is similar to that which has been described as enhancing vaccine responses. Once these prototypes are built and bench-tested, they will be then be tested side by side with the larger laser systems already shown to enhance vaccine responses. Using an established mouse vaccine model, the small laser systems will first be tested to show the treatment doses are non-harmful and non-damaging to the skin. Following this, their ability to produce equivalent immune responses to an influenza vaccination will be tested, including protection against a lethal challenge with influenza.