POLLEN GRAINS AS TROJAN HORSES FOR ORAL VACCINATION

花粉粒作为口服疫苗的特洛伊木马

• 批准号: 8356940
• 负责人: Harvinder Singh Gill
• 金额: $ 220.5万
• 依托单位: TEXAS TECH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-30 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8356940
• 关键词: Address; Adjuvant; Antibodies; Antigens; Biomedical Engineering; Cell Line; Cereals; Child; Cholera Toxin; Communicable Diseases; Data; Development; Drug Delivery Systems; Engineering; Environment; Epithelial; Epithelial Cells; Equus caballus; Goals; Gold; Human; Human body; Immune response; Immunoglobulin G; Infection; Intestines; Intramuscular; Methodology; Microbe; Modeling; Mucosal Immune Responses; Mucosal Immunity; Mucous Membrane; Mus; Needles; Oral; Ovalbumin; Painless; Pollen; Route; Serum; Stomach; Surface; Testing; Vaccination; Vaccine Antigen; Vaccines; abstracting; base; feeding; fighting; gastrointestinal; hypodermic needle; immunoregulation; interdisciplinary approach; microbial; mucosal vaccine; novel; oral vaccine; particle; pathogen; public health relevance; uptake; vaccine delivery; vaccinology

DESCRIPTION (Provided by the applicant) Abstract: We propose to transform pollen grains into a powerful and broadly applicable oral vaccination platform. Oral vaccine delivery has been a longstanding goal in the field of vaccination because it is needle-free, can be selfadministered and can produce both systemic and mucosal immune responses. Mucosal immunity is a powerful host-regulated defense at the mucosal surfaces that can neutralize pathogens while they are still outside the human body, before they can cause infection. The gastrointestinal mucosa like other mucosal surfaces suffers from constant onslaughts of microbes and forms a major portal of pathogen entry. Therefore, being able to stimulate mucosal immunity at the gastrointestinal mucosa will offer a tremendous immunological advantage to humans to help fight-off microbial invasions. The major roadblocks that continue to obstruct successful oral vaccination are the degradation of vaccines in the stomach and their poor uptake across the intestinal epithelial cell lining. Pollen grains are a natural engineering marvel with potential to address these roadblocks. Pollen grains have very tough exterior shells, which can withstand the acidic and enzymatic environment of the stomach and they can pass in to the body as intact particles across the tight epithelial cells of the gastrointestinal mucosa. We propose to exploit these fantastic natural particles and transform them into ¿Trojan horses¿ to safely ferry vaccine antigens across the harsh environment of the stomach and across the tight epithelial barrier, into the body. We have tested the feasibility of our seemingly peculiar idea by feeding mice with pollen grains filled with ovalbumin as a model antigen. Anti-ovalbumin immunoglobulin G (IgG) antibodies were produced in mouse serum after the vaccination. Importantly, the anti-ovalbumin IgG levels induced by pollen grains were found to be more than ten-fold higher than the anti-ovalbumin IgG levels induced by the use of cholera toxin (CT) as a positive control. This result is very significant because CT as a mucosal adjuvant is the current gold standard for oral vaccination and our data suggests that pollen grains are superior to CT. We are very excited by this discovery and we propose to further develop this promising strategy for oral vaccination through a multidisciplinary approach bridging the fundamentals of bioengineering, drug delivery and vaccinology. Our two complementary goals that will move this approach closer to human trials are: (i) characterize pollen grains and develop a mechanistic understanding of their Trojan ability, and (ii) understand mucosal and systemic immune responses generated by pollen grain-based oral vaccination and explore the potential of immunomodulation by the synergistic use of adjuvants. Overall, this pollen grain-based oral vaccine delivery platform is expected to be highly versatile and thus has potential to be harnessed for development of mucosal vaccines against a host of infectious diseases. Public Health Relevance: This project seeks to develop a novel methodology for oral vaccination, which is painless, child-friendly, safer and functionally superior to the exiting intramuscular route of vaccination using hypodermic needles. The delivery methodology will have broad applicability and will be able to deliver a broad range of vaccines.

描述(由申请人提供) 摘要：我们建议将花粉颗粒转化为一个功能强大、适用范围广的口服疫苗接种平台。口服疫苗接种一直是疫苗接种领域的一个长期目标，因为它是无针的，可以自我给药，可以产生全身和粘膜免疫反应。粘膜免疫是一种强大的宿主调节的粘膜表面防御，可以在病原体仍在人体外时中和它们，以免它们引起感染。胃肠粘膜像其他粘膜表面一样，不断遭受微生物的侵袭，形成病原体进入的主要门户。因此，能够在胃肠道粘膜激发粘膜免疫将为人类提供巨大的免疫优势，帮助抵御微生物的入侵。继续阻碍成功口服疫苗接种的主要障碍是疫苗在胃内的降解以及它们在肠道上皮细胞层中的低摄取率。花粉 谷物是一种天然的工程奇迹，有可能解决这些障碍。花粉颗粒有非常坚硬的外壳，可以承受胃的酸性和酶环境，它们可以作为完整的颗粒穿过胃肠道粘膜的紧密上皮细胞进入体内。我们建议利用这些奇妙的天然颗粒并将它们转化为特洛伊木马，以安全地将疫苗抗原运送到胃的恶劣环境中，穿过紧密的上皮屏障进入体内。我们用填充了卵清蛋白的花粉颗粒作为模型抗原，测试了我们这个看似奇怪的想法的可行性。免疫后小鼠血清中产生抗卵清蛋白免疫球蛋白G(Ig G)抗体。重要的是，花粉诱导的抗卵清蛋白免疫球蛋白水平比用霍乱毒素(CT)作为阳性对照诱导的抗卵清蛋白免疫球蛋白水平高10倍以上。这一结果非常有意义，因为CT作为一种粘膜佐剂是目前口服疫苗的黄金标准，我们的数据表明，花粉粒优于CT。我们对这一发现感到非常兴奋，我们建议通过一种多学科的方法进一步发展这一前景看好的口服疫苗接种战略，将生物工程、药物输送和疫苗学的基本原理联系起来。我们的两个相辅相成的目标将使这一方法更接近人体试验：(I)描述花粉颗粒的特征并发展对其特洛伊木马的机械理解 了解基于花粉颗粒的口服疫苗产生的粘膜和系统免疫反应，并探索通过协同使用佐剂进行免疫调节的潜力。总体而言，这种基于花粉颗粒的口服疫苗递送平台预计将具有高度的通用性，因此有可能被用于开发针对一系列传染病的粘膜疫苗。 公共卫生相关性：该项目寻求开发一种新的口服疫苗接种方法，该方法无痛、对儿童友好、更安全，并且在功能上优于现有的使用皮下注射针的肌肉内接种路线。提供方法将具有广泛的适用性，并将能够提供广泛的疫苗。

项目成果

Demystifying particle-based oral vaccines.

• DOI: 10.1080/17425247.2021.1946511
• 发表时间: 2021-10
• 期刊: Expert opinion on drug delivery
• 影响因子: 6.6
• 作者: Gonzalez-Cruz P;Gill HS
• 通讯作者: Gill HS

Pollen grains as a novel microcarrier for oral delivery of proteins.

• DOI: 10.1016/j.ijpharm.2018.10.016
• 发表时间: 2018-12-01
• 期刊: International journal of pharmaceutics
• 影响因子: 5.8
• 作者: Lale SV;Gill HS
• 通讯作者: Gill HS

Pollen grains for oral vaccination.

• DOI: 10.1016/j.jconrel.2014.08.010
• 发表时间: 2014-11-28
• 期刊: Journal of controlled release : official journal of the Controlled Release Society
• 作者: Atwe SU;Ma Y;Gill HS
• 通讯作者: Gill HS

Ragweed pollen as an oral vaccine delivery system: Mechanistic insights.

• DOI: 10.1016/j.jconrel.2017.10.019
• 发表时间: 2017-12-28
• 期刊: Journal of controlled release : official journal of the Controlled Release Society
• 作者: Uddin MJ;Gill HS
• 通讯作者: Gill HS

From allergen to oral vaccine carrier: A new face of ragweed pollen.

• DOI: 10.1016/j.ijpharm.2018.05.003
• 发表时间: 2018-07-10
• 期刊: International journal of pharmaceutics
• 影响因子: 5.8
• 作者: Uddin MJ;Gill HS
• 通讯作者: Gill HS