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）：该提案的总体目的是提供概念证据证据证明，新开发的原型激光系统可以导致现有流感（流感）疫苗的剂量，而无需任何添加剂。流感仍然是一个重大的公共卫生问题，全世界最多可导致3 〜500万例严重疾病和500,000例死亡。仅在美国，它每年的成本超过40亿美元。年度疫苗接种仍然是防止病毒传播并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，但是，这在经济，临床和制造业上造成了巨大的负担。这是因为与循环病毒中抗原改变相匹配的新疫苗的时间相对较短，但疫苗的需求却大大且每年都大大增加，尤其是在爆发新的流感菌株或大流行期间。疫苗佐剂可以显着降低疫苗剂量或剂量，从而大大降低成本。不幸的是，在美国，铝基辅助剂是唯一的FDA批准，广泛使用的疫苗佐剂，无法提供令人满意的增强对人类流感疫苗的免疫反应的增强。我们开发了一种原型激光系统，能够增强和延长针对基于蛋白质的疫苗的免疫反应，包括季节流感疫苗，副作用很少。我们正在探索这种激光疫苗辅助（LVA），用于剂量 - 剂量 - 季节性和大流行流感疫苗。我们将调查通过在皮内或肌肉内注射到激光暴露部位的季节流感疫苗引起的免疫保护是否等于或大于或大于在BALB/C/C和C57BL/6（B6）小鼠中类似地注入BALB/C和C57BL/6（B6）小鼠的疫苗剂量的疫苗，并在该效率上使用该效率的动物来验证该效率。在老鼠和年轻小鼠中也将进行类似的研究，以证实LVA可以将疫苗接种剂量从幼稚的小鼠中减少到1剂，并显着提高老鼠的流感疫苗接种率。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，免受一剂通过LVA和MF59辅助剂的组合提供的储存的H5N1疫苗后，保护小鼠和雪貂。激光“辅助”不需要冷链存储或对现有疫苗进行任何修改，并且可以立即并反复使用而无需限制。这些独特的角色使得这项技术是应对流感疫苗短缺的理想选择。 公共卫生相关性：在疫苗接种之前先用安全的激光对皮肤进行短暂照明可能会导致现有流感疫苗的剂量，从而每年为季节性流感疫苗的数十亿美元节省成本有效的节省，并且在流感pandemic中的季节性流感疫苗和较高的疫苗可用性。