Boosting Flu Vaccination without Adjuvant Injection

无需注射佐剂即可加强流感疫苗接种

• 批准号: 8263742
• 负责人: Mei X Wu
• 金额: $ 46.73万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-06-01 至 2016-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8263742
• 关键词: Adjuvant; Adverse effects; Aluminum; Anatomy; Animals; Antigens; Area; Autoantigens; Birds; Centers for Disease Control and Prevention (U.S.); Cessation of life; Child; Clinic; Clinical Trials; Cold Chains; Cross Reactions; Cutaneous; Development; Devices; Disease; Disease Outbreaks; Dose; Elderly; Ensure; Event; FDA approved; Face; Family suidae; Ferrets; Flu virus; Human; Immune; Immune response; Immunology; Influenza; Influenza A Virus, H1N1 Subtype; Influenza A Virus, H5N1 Subtype; Influenza vaccination; Injection of therapeutic agent; Investigation; Lasers; Lighting; MF59; Manufacturer Name; Mediating; Medicine; Miniature Swine; Modification; Morbidity - disease rate; Mus; Muscle; Physiologic pulse; Proteins; Public Health; Regimen; Respondent; Risk; Route; Savings; Seasons; Site; Skin; System; Technology; Testing; Time; Vaccination; Vaccine Adjuvant; Vaccines; Virus; Virus Diseases; base; coping; cost; cost effective; dosage; flu; influenza virus vaccine; mortality; nanosecond; new technology; novel vaccines; pandemic disease; pandemic influenza; prevent; prototype; public health relevance; seasonal influenza; success; swine flu

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.

描述(由申请人提供)：这项建议的总体目标是提供概念证据，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节省现有流感(流感)疫苗的剂量。流感仍然是一个重大的公共卫生问题，每年在全球范围内造成多达300万至500万例严重疾病和50万人死亡。仅在美国，每年就要花费超过40亿美元。每年接种疫苗仍然是防止病毒传播和降低流感引起的发病率和死亡率的最具成本效益的手段之一，但这在经济、临床和制造方面都造成了巨大的负担。这是因为新疫苗与正在传播的病毒中的抗原变化匹配的时间相对较短，但疫苗需求巨大，而且每年都在急剧增加，特别是在新的流感病毒株或大流行爆发期间。疫苗佐剂可以显著减少疫苗剂量或剂量，极大地降低成本。不幸的是，铝佐剂是FDA批准的唯一在美国广泛使用的疫苗佐剂，未能在人类身上提供令人满意的流感疫苗免疫反应增强。我们开发了一个原型激光系统，能够增强和延长对蛋白质疫苗的免疫反应，包括季节性流感疫苗，副作用很小。我们正在探索这种激光疫苗佐剂(LVA)，用于节省现有季节性和大流行流感疫苗的剂量。我们将研究低剂量季节性流感疫苗皮内或肌肉内注射到激光照射部位所产生的免疫保护是否等于或大于在Balb/c和C57BL/6(B6)小鼠以及小型猪身上注射类似的高剂量疫苗所产生的免疫保护，以验证这项技术在不同皮肤的不同动物物种中的可行性。一项类似的研究也将在老年和幼龄小鼠身上进行，以证实LVA可以将幼龄小鼠的疫苗接种剂量从2减少到1，并显著提高老年小鼠接种流感疫苗的应答率。最后，我们将把研究扩展到H5N1大流行流感疫苗，保护小鼠和雪貂免受高致病性H5N1禽流感病毒的致命挑战，因为一剂库存的H5N1疫苗是通过LVA和MF59佐剂的组合提供的。这种激光“佐剂”不需要冷链储存，也不需要对现有疫苗进行任何修改，而且可以立即、无限制地重复使用。这些独特的特点使这项技术成为应对流感疫苗短缺的理想选择。 与公共卫生相关：接种疫苗前用安全激光对皮肤进行短暂照射可能会节省现有流感疫苗的剂量，从而每年节省数十亿美元的季节性流感疫苗成本效益，并在流感大流行情况下提高疫苗的可获得性。