Boosting Flu Vaccination without Adjuvant Injection

描述（由申请人提供）：本提案的总体目标是提供概念证明证据，证明新开发的原型激光系统可以在不添加任何添加剂的情况下减少现有流感疫苗的剂量。流感仍然是一个重大的公共卫生问题，每年在世界范围内造成多达300万至500万例严重疾病和50万人死亡。仅在美国，每年的医疗费用就超过40亿美元。每年接种疫苗仍然是预防病毒传播和减少流感引起的发病率和死亡率的最具成本效益的手段之一，然而，这在经济、临床和生产方面造成了巨大的负担。这是因为与流行病毒抗原变化相匹配的新疫苗的开发时间相对较短，但疫苗需求量巨大，而且每年都在急剧增加，特别是在新病毒株爆发或流感病毒大流行期间。疫苗佐剂可以显著减少疫苗剂量或剂量，大大降低成本。不幸的是，铝基佐剂，唯一的fda批准，在美国广泛使用的疫苗佐剂，未能提供令人满意的增强人类流感疫苗的免疫反应。我们开发了一种原型激光系统，能够增强和延长对基于蛋白质的疫苗（包括季节性流感疫苗）的免疫反应，而且副作用很少。我们正在探索这种激光疫苗佐剂（LVA）用于现有季节性和大流行性流感疫苗的剂量节约。我们将研究在Balb/c和C57BL/6 （B6）小鼠和小型猪中，低剂量的季节性流感疫苗皮内注射或肌肉注射到激光照射部位所引起的免疫保护是否等于或大于高剂量的疫苗注射所引起的免疫保护，以验证该技术在不同皮肤的不同动物物种中的可行性。还将在老年和年轻小鼠中进行类似的研究，以证实LVA可以将幼年小鼠的疫苗接种剂量从两剂减少到一剂，并显着提高老年小鼠的流感疫苗接种率。最后，我们将把研究范围扩大到H5N1大流行性流感疫苗，在通过LVA和MF59佐剂组合给药一剂储存的H5N1疫苗后，保护小鼠和雪貂免受高致病性H5N1禽流感病毒的致命攻击。激光“佐剂”不需要冷链储存，也不需要对现有疫苗进行任何修改，可以立即重复使用，没有限制。这些独特的特性使这项技术成为应对流感疫苗短缺的理想选择。

DESCRIPTION (provided by applicant): The overall objective of this proposal is to provide proof of concept evidence that a newly-developed prototype laser system can result in dose-sparing of existing influenza (flu) vaccines without any additives. Flu continues to be a significant public health problem and is responsible for up to 3~5 million cases of severe disease and 500,000 deaths a year worldwide. It costs more than 4 billion dollars a year in the US alone. Annual vaccination still remains one of the most cost-effective means to prevent the spread of the virus and decrease flu-caused morbidity and mortality, which, however, creates a huge burden economically, clinically and manufacturally. That is because time of a new vaccine matching the antigen alteration in the circulating virus is relatively short and yet the vaccine demand is massive and continuously increasing drastically every year, in particular, during an outbreak of a new strain or pandemic of flu virus. Vaccine adjuvant can significantly reduce vaccine doses or dosages, reducing the cost enormously. Unfortunately, aluminum-based adjuvant, the only FDA-approved, widely used vaccine adjuvant in the US, failed to provide satisfactory augmentation of immune responses for flu vaccines in humans. We develop a prototype laser system capable of enhancing and prolonging immune responses against protein-based vaccines including season flu vaccine with few side effects. We are exploring this laser vaccine adjuvant (LVA) for dose- sparing of existing seasonal and pandemic flu vaccines. We will investigate whether immune protection elicited by a low dosage of season flu vaccine intradermally or intramuscularly injected into a site of laser exposure is equal to or greater than that induced by a higher dosage of the vaccine injected similarly in Balb/c and C57BL/6 (B6) mice and in minipigs to verify the feasibility of this technology in different animal species with varying skins. A similar study will also be conducted in old and young mice to corroborate that LVA can reduce vaccination doses from two to one in naive young mice and significantly enhance a respondent rate of flu vaccination in old mice. Finally, we will extend the investigation to H5N1 pandemic flu vaccine, protecting mice and ferrets from a lethal challenge of a highly pathogenic avian H5N1 flu virus after one dose of the stockpiled H5N1 vaccine delivered via a combination of LVA and MF59 adjuvant. The laser "adjuvant" does not need cold chain storage or any modification to the existing vaccines, and it can be used immediately and repeatedly without a limit. These unique characters make this technology ideal for coping with flu vaccine shortages. PUBLIC HEALTH RELEVANCE: Brief illumination of the skin with a safe laser before vaccination may result in dose-sparing of existing influenza vaccines, leading to cost-effective savings in billions of dollars each year for seasonal flu vaccines, and higher vaccine availability in the event of an influenza pandemic.