Vaginal Immunity After Intranasal Listeria Vaccination

鼻内李斯特菌疫苗接种后的阴道免疫力

• 批准号: 7334102
• 负责人: Fred Robert Frankel
• 金额: $ 23.63万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-01 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7334102
• 关键词: Acquired Immunodeficiency Syndrome; Acute; Antigens; Appearance; Attenuated; Attenuated Vaccines; CD8B1 gene; Cellular Immunity; Chronic; Clinical; Disease Outcome; Disease Progression; Dose; Epithelial; Epithelium; Escape Mutant; Event; Female; Generations; Genital system; HIV; HIV Infections; HIV vaccine; Helper-Inducer T-Lymphocyte; Human; Human Volunteers; Immune response; Immunity; Immunization; Immunobiology; Infection; Intestines; Intravenous; Life; Listeria; Listeria monocytogenes; Listeriosis; Literature; Maintenance; Malignant neoplasm of cervix uteri; Modeling; Mucous Membrane; Nose; Oral; Oral Administration; Play; Process; Recombinants; Reporting; Resistance; Role; Route; Safety; Site; Structure of mucous membrane of nose; Surface; T-Lymphocyte; Testing; Vaccination; Vaccines; Vagina; Viral; Viral Load result; Viremia; Virus; Woman; fortification; men; mucosal site; neutralizing antibody; oral infection; pressure; rectal; response; transmission process

DESCRIPTION (provided by applicant): The epithelial layer is both the site of attack and the first line of defense for most HIV infections. Unfortunately, this defense is breachable. Half of the 42 million people living with HIV are women infected vaginally and most of the remainder are men infected through the rectal epithelium. Fortification of these mucosal surfaces should be a priority for HIV vaccines. Cellular immunity plays a profound role in controlling disease progression but ultimately proves unsuccessful since it develops too slowly. Active local immunity could block the earliest infection events at mucosae and the spread of virus from these sites. While the generation of neutralizing antibodies against primary HIV isolates is problematic, several agents can reliably elicit the induction of cellular immunity. Since nasal immunization has often been shown to generate vaginal immune responses, we are proposing to explore the use of Listeria monocytogenes (Lm), an agent known to induce strong cellular immunity, as a nasal vaccine for HIV. One report has already shown that intranasal (IN) immunization with Lm is effective for generating resistance to high dose intranasal or intravenous Lm challenge. Our own preliminary studies confirm this, and show that the nasal mucosa is even more sensitive than the gut to infection and translocation by Lm. We propose to examine the early cellular immune responses to IN Lm infection and importantly, test both the safety of this approach and the prediction that the protective efficacy of IN immunization with live, attenuated Lm vaccine strains will extend to the female genital tract. In combination with oral inoculation, recombinant strains of Lm may result in protection of vaginal, intestinal and rectal surfaces against HIV infection.

描述（由申请人提供）：上皮层既是攻击部位，也是大多数HIV感染的第一道防线。不幸的是，这种辩护是可违反的。艾滋病毒感染的4200万人中有一半是被阴道感染的女性，其余的大多数是通过直肠上皮感染的男性。这些粘膜表面的防御力应该是HIV疫苗的优先事项。细胞免疫在控制疾病进展中起着极大的作用，但最终证明其发展得太慢，因此没有成功。积极的局部免疫力可以阻止粘膜上最早的感染事件以及病毒从这些部位传播。尽管对原发性HIV分离株的中和抗体产生是有问题的，但几种药物可以可靠地引起细胞免疫的诱导。由于经常证明鼻腔免疫会产生阴道免疫反应，因此我们建议探索单核细胞增生李斯特菌的使用（LM），一种已知诱导强细胞免疫的剂，作为HIV的鼻疫苗。一份报告已经表明，LM内鼻内（IN）免疫可有效产生对高剂量鼻内或静脉内LM挑战的抗性。我们自己的初步研究证实了这一点，并表明鼻粘膜比肠道对LM感染和易位更敏感。我们建议检查对LM感染中的早期细胞免疫反应，并重要地测试这种方法的安全性，以及预测的预测，即通过活着，减弱的LM疫苗菌株在免疫中的保护功效将延伸至女性生殖道。结合口服接种，LM的重组菌株可能会导致阴道，肠和直肠表面免受HIV感染的保护。