Nasal Vaccines: Mode of Action, Composition & Delivery

鼻用疫苗有可能成为有效、经济、无针头的方法。 免疫能够诱导系统免疫和粘膜免疫。鼻腔免疫可能会安全 以及针对新发传染病和选定病原体的有效疫苗接种。虽然 在制定鼻腔免疫策略方面取得了进展，更好地了解了 需要鼻用疫苗佐剂的投放地点(S)和作用方式(S)。它不是 明确鼻用疫苗佐剂是否通过激活粘膜上皮或免疫细胞而显示佐剂活性 在上皮下隔室。此外，虽然小鼠鼻免疫可诱导全身免疫 在大小上可与非肠道免疫、鼻腔免疫相当 兔或非人类灵长类动物在诱导抗原方面不如肠外免疫有效。 特异性血清免疫球蛋白。我们推测，鼻腔免疫在兔和非人类中缺乏效力 灵长类是由于对非灵长类动物上呼吸道免疫诱导组织缺乏了解所致 啮齿动物和对疫苗鼻腔注射后的解剖分布和方法的有限了解 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，需要更多的临床前毒性研究来评估有效的鼻用疫苗的安全性。 配方。我们的长期目标是开发安全有效的鼻用疫苗，用于 人类。我们的具体目标是： 具体目的一：确定鼻用疫苗佐剂IL-1a和TLR4配体RC-529的作用方式 自动对焦。这将在一系列实验中得到解决，以调查粘膜佐剂是否激活(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：确定疫苗交付的解剖位置和清除时间 在小鼠、大鼠和兔子身上以水或干粉的形式鼻腔给药，并确定是否给药 而清除与系统或粘膜中抗原特异性免疫的诱导有关。 车厢。

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.