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: 8510563
• 负责人: Mei X Wu
• 金额: $ 44.47万
• 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/8510563
• 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.

描述（由申请方提供）：本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含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，每年在全世界造成多达300万至500万例严重疾病和50万例死亡。仅在美国每年就花费超过40亿美元。每年接种疫苗仍然是预防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，这在经济上、临床上和制造业上造成了巨大的负担。这是因为与流行病毒中的抗原改变相匹配的新疫苗的时间相对较短，然而疫苗需求是巨大的，并且每年持续急剧增加，特别是在流感病毒的新毒株或大流行的爆发期间。疫苗佐剂可以显著降低疫苗剂量或用量，极大地降低成本。不幸的是，基于铝的佐剂，唯一FDA批准的，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应答。我们开发了一种原型激光系统，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，副作用少。我们正在探索这种激光疫苗佐剂（LVA），以节省现有季节性流感和大流行性流感疫苗的剂量。我们将研究通过皮内或肌内注射低剂量季节性流感疫苗到激光照射部位引起的免疫保护是否等于或大于Balb/c和C57 BL/6（B6）小鼠和小型猪中类似注射的较高剂量疫苗引起的免疫保护，以验证该技术在不同皮肤的不同动物物种中的可行性。还将在老年小鼠和年轻小鼠中进行类似的研究，以证实LVA可以将幼稚的年轻小鼠的疫苗接种剂量从两个减少到一个，并显着提高老年小鼠的流感疫苗接种应答率。最后，我们将把研究扩展到H5 N1大流行性流感疫苗，通过LVA和MF 59佐剂的组合，在一剂储存的H5 N1疫苗后，保护小鼠和雪貂免受高致病性禽H5 N1流感病毒的致命攻击。激光“佐剂”不需要冷链储存或对现有疫苗进行任何修改，并且可以立即使用和重复使用，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。