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：我们建议将花粉粒转变为强大且广泛适用的口服疫苗平台。口服疫苗递送一直是疫苗接种领域的长期目标，因为它是无针的，可以自行给药，并且可以产生全身和粘膜免疫反应。粘膜免疫是粘膜表面强大的宿主调节防御，可以在病原体引起感染之前中和仍在人体外的病原体。胃肠粘膜像其他粘膜表面一样遭受微生物的持续攻击，并形成病原体进入的主要门户。因此，能够刺激胃肠粘膜的粘膜免疫将为人类提供巨大的免疫优势，帮助抵御微生物入侵。继续阻碍口服疫苗成功的主要障碍是疫苗在胃中的降解以及它们在肠上皮细胞内壁的吸收不良。花粉 谷物是一种天然的工程奇迹，有可能解决这些障碍。花粉粒具有非常坚韧的外壳，可以承受胃的酸性和酶环境，并且可以作为完整的颗粒穿过胃肠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穿过胃的恶劣环境并穿过紧密的上皮屏障进入体内。我们通过给小鼠喂食充满卵清蛋白作为模型抗原的花粉粒来测试我们看似奇特的想法的可行性。接种疫苗后，小鼠血清中产生抗卵清蛋白免疫球蛋白 G (IgG) 抗体。重要的是，发现花粉粒诱导的抗卵清蛋白 IgG 水平比使用霍乱毒素 (CT) 作为阳性对照诱导的抗卵清蛋白 IgG 水平高十倍以上。这一结果非常重要，因为 CT 作为粘膜佐剂是当前口服疫苗接种的金标准，而且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，我们建议通过连接生物工程、药物输送和疫苗学基础知识的多学科方法，进一步开发这一有前景的口服疫苗策略。我们的两个互补目标将使这种方法更接近人体试验：(i) 表征花粉粒并对其特洛伊木马产生机械理解 能力，以及（ii）了解基于花粉粒的口服疫苗产生的粘膜和全身免疫反应，并探索佐剂协同使用的免疫调节潜力。总体而言，这种基于花粉粒的口服疫苗递送平台预计将具有高度通用性，因此有潜力用于开发针对多种传染病的粘膜疫苗。 公共卫生相关性：该项目旨在开发一种新的口服疫苗接种方法，该方法无痛、儿童友好、更安全且功能优于现有的皮下注射针头肌肉注射疫苗接种途径。该递送方法将具有广泛的适用性，并且能够递送广泛的疫苗。

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

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

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