Nasal Vaccines: Mode of Action, Composition & Delivery

鼻腔疫苗：作用方式、成分

• 批准号: 8069023
• 负责人: Herman F Staats
• 金额: $ 13.76万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-10 至 2011-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8069023
• 关键词: Address; Adjuvant; Antigens; Cells; Dendritic Cells; Development; Drug Formulations; Emerging Communicable Diseases; Epithelium; Exhibits; Goals; Human; Immune; Immune response; Immunity; Immunization; Immunoglobulin G; Knowledge; Ligands; Lymphocyte; Methods; Mucosal Immunity; Mus; Needles; Nose; Oryctolagus cuniculus; Powder dose form; Rattus; Rodent; Safety; Series; Serum; Site; Stromal Cells; TLR4 gene; Time; Tissues; Upper respiratory tract; Vaccination; Vaccine Adjuvant; Vaccines; aqueous; nonhuman primate; pathogen; preclinical toxicity; research study; residence

Nasally administered vaccines have the potential to be effective, economical, needle-free methods of immunization able to induce both systemic and'mucosal immunity. Nasal immunization may allow for safe and effective vaccination against emerging infectious diseases and select agent pathogens. Although progress has been made in the development of nasal immunization strategies, a better understanding of the site(s) of delivery and mode(s) of action of adjuvants for nasally-administered vaccines is needed. It is not clear if nasal vaccine adjuvants exhibit adjuvant activity by activating the mucosal epithelium or immune cells in the subepithelial compartment. Additionally, while nasal immunization of mice induces systemic immune responses comparable in magnitude to those induced by parenteral immunization, nasal immunization of rabbits or non-human primates is not as effective as parenteral immunization for the induction of antigen- specific serum IgG. We postulate that the lack of efficacy of nasal immunization in rabbits and non-human primates is due to poor understanding of the immune inductive tissues of the upper respiratory tract in non- rodents and limited knowledge of the anatomical distribution of vaccines after nasal delivery and methods of controlling their residence time. Finally, nasal vaccines and adjuvants must be both effective and safe. Therefore, additional preclinical toxicity studies are needed to evaluate the safety of effective nasal vaccine formulations. Our long term goal is to develop safe and effective nasally administered vaccines for use in humans. Our specific aims are: Specific Aim One: Determine the mode of action of nasal vaccine adjuvants IL-1a and TLR4 ligand RC-529 AF. This will be addressed in a series of experiments to investigate if mucosal adjuvants activate (a) the mucosal stromal cells or (b) subepithelium dendritic cells or lymphocytes. Specific Aim Two: Identify the anatomical site of delivery and time of clearance of vaccines when delivered nasally as aqueous or dry-powder formulations in mice, rats and rabbits and determine if delivery and clearance correlates with the induction of antigen-specific immunity in the systemic or mucosal compartment.

鼻腔注射疫苗有可能成为有效、经济、无针的方法 免疫能够诱导全身免疫和粘膜免疫。鼻腔免疫接种可确保安全 针对新发传染病和特定病原体的有效疫苗接种。虽然 鼻腔免疫策略的制定取得了进展，人们更好地了解了鼻腔免疫策略 需要鼻腔疫苗佐剂的递送部位和作用方式。它不是 明确鼻疫苗佐剂是否通过激活粘膜上皮或免疫细胞而表现出佐剂活性 在上皮下室。此外，虽然小鼠鼻腔免疫可诱导全身免疫 反应的强度与肠外免疫、鼻腔免疫引起的反应相当 兔子或非人灵长类动物在诱导抗原方面不如肠胃外免疫有效。 特异性血清 IgG。我们假设鼻腔免疫对兔子和非人类动物缺乏功效 灵长类动物的免疫诱导组织对非灵长类动物的上呼吸道免疫诱导组织了解甚少。 啮齿类动物以及对鼻腔给药后疫苗的解剖分布和接种方法的了解有限 控制他们的停留时间。最后，鼻用疫苗和佐剂必须既有效又安全。 因此，需要额外的临床前毒性研究来评估有效鼻疫苗的安全性 配方。我们的长期目标是开发安全有效的鼻腔疫苗，用于 人类。我们的具体目标是： 具体目标一：确定鼻疫苗佐剂IL-1a和TLR4配体RC-529的作用方式 AF。这将通过一系列实验来解决，以研究粘膜佐剂是否激活（a） 粘膜基质细胞或(b)上皮下树突状细胞或淋巴细胞。 具体目标二：确定疫苗的递送解剖部位和清除时间 以水性或干粉制剂的形式经鼻递送至小鼠、大鼠和兔子，并确定是否递送 清除率与全身或粘膜中抗原特异性免疫的诱导相关 隔间。

项目成果

Dry powder vaccines for mucosal administration: critical factors in manufacture and delivery.

用于粘膜给药的干粉疫苗：制造和交付的关键因素。

• DOI: 10.1007/82_2011_167
• 发表时间: 2012
• 期刊: Current topics in microbiology and immunology
• 作者: Wang,SheenaH;Thompson,AftonL;Hickey,AnthonyJ;Staats,HermanF
• 通讯作者: Staats,HermanF

Polymer hydrogels: Chaperoning vaccines.

• DOI: 10.1038/nmat2788
• 发表时间: 2010-07
• 期刊: Nature materials
• 影响因子: 41.2
• 作者: H. Staats;K. Leong

Effective induction of protective systemic immunity with nasally administered vaccines adjuvanted with IL-1.

• DOI: 10.1016/j.vaccine.2010.08.006
• 发表时间: 2010-10-04
• 期刊: VACCINE
• 影响因子: 5.5
• 作者: Gwinn, William M.;Kirwan, Shaun M.;Wang, Sheena H.;Ashcraft, Kathleen A.;Sparks, Neil L.;Doil, Catherine R.;Tlusty, Tom G.;Casey, Leslie S.;Hollingshead, Susan K.;Briles, David E.;Dondero, Richard S.;Hickey, Anthony J.;Foster, W. Michael;Staats, Herman F.
• 通讯作者: Staats, Herman F.