An Inactivated Influenza Nasal Powder Vaccine

灭活流感鼻粉疫苗

• 批准号: 6845198
• 负责人: Yawei Ni
• 金额: $ 606.11万
• 依托单位: DELSITE BIOTECHNOLOGIES, INC.
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-30 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6845198
• 关键词: bioterrorism /chemical warfare; cooperative study; dosage forms; drug preservation; ferrets; influenza vaccines; inhalation drug administration; laboratory rat; mucosal immunity; polysaccharides; vaccine development; vaccine evaluation; virion; virus antigen

DESCRIPTION (provided by applicant): Intranasal immunization can induce not only systemic, but also mucosal immunity, is easy to administer, and is suitable for mass immunization. These advantages of nasal immunization are particularly relevant to influenza virus which affects respiratory mucosal surfaces and constantly poses the danger of a pandemic. Inactivated influenza antigens however, are poor immunogens by themselves when delivered via the intranasal route. Our objective is to develop an inactivated whole virion influenza nasal powder vaccine incorporating a novel in-situ gelling nasal delivery system (GelVac(tm)). Vaccines containing whole virion antigens are more immunogenic and faster to manufacture. Being inactivated, this vaccine does not have the shortcomings of a live vaccine. Furthermore, powder formulations have critical advantages as a biodefense tool, including better stability and cold-chain-free distribution. Thus, the advantages of inactivated whole virion antigen, powder formulation, and nasal delivery with the GelVac system are combined together in this one vaccine. The GelVac system utilizes an enabling excipient and is an integral part of this vaccine. It is based on the GelSite(tm) polymer, a unique acidic high molecular weight plant polysaccharide currently manufactured under cGMP. It confers two critical properties to the vaccine: mucoadhesive and in-situ gelling - changing from a powder to a gel upon contact with nasal fluid and thereby providing a sustained antigen release. Our preliminary studies have shown that intranasal delivery with GelVac powder formulations significantly increases serum IgG and lung IgA responses against inactivated split subvirion influenza antigen. The proposed studies include 1) formulation development, 2) immunogenicity and protection, and 3) animal toxicity studies. Two vaccine candidates, a monovalent H5 subtype and a trivalent consisting of the three virus strains in current inactivated influenza vaccines, will be developed. Completion of these preclinical studies will form the basis for an IND submission.

说明（申请人提供）：鼻内免疫既能诱导全身免疫，又能诱导粘膜免疫，给药方便，适用于大规模免疫。鼻免疫的这些优势与流感病毒特别相关，流感病毒会影响呼吸道粘膜表面并不断构成大流行的危险。然而，当通过鼻内途径递送时，灭活的流感抗原本身是弱免疫原。 我们的目标是开发一种灭活的全病毒粒子流感鼻粉剂疫苗，该疫苗结合了一种新型的原位胶凝鼻递送系统（GelVac（TM））。含有完整病毒体抗原的疫苗具有更高的免疫原性，并且生产更快。由于是灭活的，这种疫苗没有活疫苗的缺点。此外，粉末制剂作为生物防御工具具有关键优势，包括更好的稳定性和无冷链分布。因此，灭活的全病毒体抗原、粉末制剂和使用GelVac系统的鼻递送的优点在这一疫苗中组合在一起。 GelVac系统使用赋形剂，是该疫苗的组成部分。它是基于GelSite（TM）聚合物，一种独特的酸性高分子量植物多糖，目前在cGMP下生产。它赋予疫苗两个关键特性：粘膜粘附和原位胶凝-在与鼻液接触时从粉末变为凝胶，从而提供持续的抗原释放。我们的初步研究表明，用GelVac粉末制剂鼻内递送显著增加了针对灭活的裂解亚病毒体流感抗原的血清IgG和肺伊加应答。 拟定研究包括1）制剂开发，2）免疫原性和保护，以及3）动物毒性研究。将开发两种候选疫苗，单价H5亚型和由当前灭活流感疫苗中的三种病毒株组成的三价疫苗。这些临床前研究的完成将构成IND提交的基础。