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）：该提案的总体目标是提供概念验证证据，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，每年在全球造成多达 3~500 万例严重疾病和 50 万人死亡。仅在美国一年的费用就超过 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，然而，这在经济、临床和生产方面造成了巨大的负担。这是因为新疫苗与流行病毒中的抗原变化相匹配的时间相对较短，但疫苗需求却很大，并且每年都在急剧增加，特别是在流感病毒新毒株爆发或大流行期间。疫苗佐剂可以显着减少疫苗的剂量或剂量，极大地降低成本。不幸的是，铝佐剂是唯一经 FDA 批准、在美国广泛使用的疫苗佐剂，未能令人满意地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，能够增强和延长针对蛋白质疫苗（包括季节性流感疫苗）的免疫反应，且副作用很少。我们正在探索这种激光疫苗佐剂（LVA），以节省现有季节性和大流行性流感疫苗的剂量。我们将研究在Balb/c和C57BL/6（B6）小鼠和小型猪中皮内或肌肉注射低剂量季节性流感疫苗所引起的免疫保护是否等于或大于类似注射的较高剂量疫苗所引起的免疫保护，以验证该技术在不同皮肤的不同动物物种中的可行性。一项类似的研究还将在年老和年幼的小鼠中进行，以证实 LVA 可以将幼年小鼠的疫苗接种剂量从 2 剂减少到 1 剂，并显着提高年老小鼠流感疫苗接种的反应率。最后，我们将研究范围扩大到 H5N1 大流行性流感疫苗，通过 LVA 和 MF59 佐剂组合注射一剂储存的 H5N1 疫苗后，保护小鼠和雪貂免受高致病性禽 H5N1 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改造，可以立即、无限制地重复使用。这些独特的特征使该技术成为应对流感疫苗短缺的理想选择。 公共卫生相关性：接种疫苗前用安全激光短暂照射皮肤可能会节省现有流感疫苗的剂量，从而每年为季节性流感疫苗节省数十亿美元的成本效益，并在流感大流行时提高疫苗的可用性。