Targeting the oral cavity epithelium for inducing mucosal immunity against HIV

靶向口腔上皮诱导针对 HIV 的粘膜免疫

基本信息

批准号：
8249376
负责人：
Harvinder Singh Gill
金额：
$ 10.61万
依托单位：
TEXAS TECH UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-04-01 至 2014-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8249376
关键词：
Address Animal Model Antibodies Antigen-Presenting Cells Antigens Binding Biological Assay Biological Preservation Child Commit Complementarity Determining Regions DNA Data Dendritic Cells Disease Distal Distant Drug Delivery Systems Drug Formulations Engineering Enzyme-Linked Immunosorbent Assay Epithelium Excipients Film Generations Gills Gingivitis Goals HIV HIV Envelope Protein gp120 HIV vaccine HIV-1 Health Sciences Housing Human Milk Hypersensitivity Immune response Immunization Immunocompetence Infant Infection Intercellular Fluid Intramuscular Irrigation Knowledge Laboratories Langerhans cell Liquid substance Lymphoid Tissue Manuscripts Measurement Measures Mentors Mentorship Metals Methodology Methods Microbiology Microscopic Milk Mothers Mouth Diseases Mucosal Immune Responses Mucosal Immunity Mucous Membrane Needles Newborn Infant Oral cavity Oral mucous membrane structure Oregon Oryctolagus cuniculus Outcome Painless Plasmids Preparation Primates Reagent Research Research Personnel Route Saliva Serum Skin Solid Staging Surface T-Lymphocyte Technology Testing Texas Time Tissues Tonsil Training United States National Institutes of Health Universities Vaccination Vaccine Research Vaccines Vagina Vaginal Douching Vertical Disease Transmission Viral Antigens Virus-like particle Work antigen processing base experience gp160 graduate student immunogenicity influenza virus vaccine malignant mouth neoplasm minimally invasive mucosal vaccination neutralizing antibody novel oral cavity epithelium pathogen post-doctoral training prevent professor public health relevance rectal response sublingual immunotherapy success transmission process vaccination strategy vaccine delivery vaginal fluid

项目摘要

DESCRIPTION (provided by applicant): In 2008, about 70,000 new infants were infected with human immunodeficiency virus (HIV) due to transmission of HIV from mother to child through the breast milk. Our goal is to induce HIV-neutralizing antibodies in the saliva to enable neutralization of HIV in the milk and prevent HIV transmission from mother to child. To achieve this goal we will exploit the natural immunocompetence of the oral cavity (OC). The OC is naturally endowed with many lymphoid tissues, such as tonsils, and with dendritic cells (DCs) in the mucosal tissue. DCs are potent antigen presenting cells that can help induce strong mucosal immunity by processing the antigen and presenting it to T-cells resident in the lymphoid tissues. In the OC there is a DC- rich zone, which is located in the upper few hundred micrometers of the OC mucosal epithelia. We will engineer and develop a vaccination approach based on microscopic needles called microneedles (MNs) that can target vaccines in close proximity to the DCs with microprecision. MNs were originally developed for painless vaccination through the skin. We postulate that MNs can be optimized to enable rapid and efficient delivery of vaccines to the oral epithelium and can generate mucosal and systemic responses. We will develop vaccine-coated MNs such that they can deliver their coatings in the DC-rich region of the OC epithelium. The objectives of this application are two fold: (i) to characterize and optimize microneedle coatings to achieve high antigen stability and delivery efficiency and (ii) to compare OC and intramuscular (IM) routes of immunization in rabbits using well characterized HIV antigens with focus on anti-HIV antibodies in the saliva, and at other distal mucosa. We will use serum, saliva, rectal fluids and vaginal fluids to compare systemic and mucosal immune responses through measurement of antigen specific antibodies and neutralizing antibodies against HIV-1. The outcomes expected from this research include a method for efficient and minimally invasive delivery of vaccines to OC epithelium, and an understanding of humoral mucosal immune response locally in the OC, at other distant mucosal surfaces and in the systemic compartment. These results are anticipated to advance the field of OC vaccination by providing fundamental new knowledge of OC immune responses from local HIV vaccine delivery. The new knowledge may also be applicable to other immuno-pathological conditions of the mouth such as oral cancer and gingivitis. PUBLIC HEALTH RELEVANCE: This project seeks to develop a novel methodology to deliver HIV vaccines to the OC and induce neutralizing antibodies in the saliva with the goal of stopping transmission of HIV from mother to child. The delivery methodology will have broad application with respect to other local diseases of the mouth such as periodontal and gum diseases.

描述（由申请人提供）：2008年，由于艾滋病毒通过母乳从母亲到儿童传播，大约有70,000名新婴儿感染了人类免疫缺陷病毒（HIV）。我们的目标是诱导唾液中的HIV中和抗体，以使牛奶中的HIV中和，并防止艾滋病毒从母亲到孩子的传播。为了实现这一目标，我们将利用口腔（OC）的自然免疫能力。 OC自然赋予许多淋巴组织，例如扁桃体，以及粘膜组织中的树突状细胞（DC）。 DC是有效的抗原呈现细胞，可以通过处理抗原并将其呈现给驻留在淋巴组织中的T细胞来帮助诱导强粘膜免疫。在OC中，有一个DC-富区，该区域位于OC粘膜上皮的上部几百微米中。我们将基于称为微针（MNS）的显微针针（MNS）来设计和开发一种疫苗接种方法，该方法可以靶向具有微分解的DC，以靠近DC。 MN最初是为通过皮肤无痛疫苗而开发的。我们假设可以优化MN，以使疫苗能够快速有效地传递到口服上皮，并可以产生粘膜和全身反应。我们将开发出疫苗包被的MN，以便它们可以在OC上皮的DC富区域输送涂料。该应用程序的目标是两倍：（i）表征和优化微针涂层，以实现高抗原稳定性和交付效率，以及（ii），使用良好的HIV抗原在兔子中使用良好特征的HIV抗原在saliva和其他saliva中的抗HIV抗体进行了OC和肌肉内（IM）免疫途径，以及其他saliva和其他远处mucosa。我们将使用血清，唾液，直肠液和阴道液来通过测量抗原特异性抗体并中和针对HIV-1的抗体来比较全身和粘膜免疫反应。这项研究的预期包括一种方法，可以在其他远处的粘膜表面和系统性的隔室中对疫苗的有效和微创输送到OC上皮的递送以及对体液粘膜免疫反应的理解。预计这些结果将通过提供局部HIV疫苗的OC免疫反应的基本知识来推动OC疫苗接种领域。新知识也可能适用于口腔癌和牙龈炎等口腔的其他免疫病理条件。公共卫生相关性：该项目旨在开发一种新颖的方法，以向OC传递HIV疫苗并诱导唾液中中和抗体中和抗体，目的是停止HIV从母亲到孩子的传播。递送方法将在其他局部疾病（例如牙周和牙龈疾病）方面具有广泛的应用。

项目成果

期刊论文数量（2）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Vaccine delivery to the oral cavity using coated microneedles induces systemic and mucosal immunity.

DOI：
10.1007/s11095-014-1335-1
发表时间：
2014-09
期刊：
PHARMACEUTICAL RESEARCH
影响因子：
3.7
作者：
Ma, Yunzhe;Tao, Wenqian;Krebs, Shelly J.;Sutton, William F.;Haigwood, Nancy L.;Gill, Harvinder S.
通讯作者：
Gill, Harvinder S.

Coating solid dispersions on microneedles via a molten dip-coating method: development and in vitro evaluation for transdermal delivery of a water-insoluble drug.