EFFECT OF STEROID HORMONES ON GENITAL IMMUNITY

避孕疫苗将为妇女提供一种简单的策略， 家庭控制其生殖生活， 怀孕开发成功的避孕疫苗需要 在生殖道产生免疫反应的能力。为了使 这项工作的进展，我们必须确定最好的技术， 生殖道免疫恒河猴的生殖生理与解剖 猕猴与人类非常相似。几乎没有做任何工作， 定义女性和非人类生殖道的正常免疫系统 灵长类动物 很明显，局部免疫反应对阴道 施用的抗原发生在女性和恒河猴中， 局部免疫系统的细胞成分存在于下丘脑中， 女性和恒河猴的生殖道。最近，我们 对女性生殖道的了解有了长足的进步 通过研究恒河猴的免疫学。的技术和测定， 我们的实验室可以很容易地进行调整，以协助努力， 对避孕疫苗有很强的免疫力。在拟议的研究中， 我们将用于免疫的抗原将包括不相关的抗原 例如破伤风类毒素和霍乱毒素，以及相关抗原，例如 精子表面蛋白PH-20将使用无关抗原 因为我们对猴子的免疫反应有丰富的经验 这些抗原，他们将作为一个有用的基线，以衡量免疫 对PH-20的反应。此外，我们将使用其他抗原， 被证明是有用的避孕疫苗，因为它们是由 这个中心的其他成员。避孕疫苗实验 基于精子抗原的研究表明， 在啮齿类动物中产生有效的免疫力。然而，目前的研究 非人灵长类动物对这种病毒只产生了中等程度的免疫应答， 相同的抗原。该项目的一个主要目标是确定时间是否 免疫与月经周期的关系影响生殖道 恒河猴的免疫反应。此外，我们将确定， 给予外源性类固醇激素可以加强和指导 粘膜部位的免疫反应。 该项目的总体目标是 开发新的免疫策略， 非人类灵长类动物生殖道的反应。

A contraceptive vaccine would provide a simple strategy for women and families to gain control of their reproductive lives and prevent undesired pregnancy. Development of a successful contraceptive vaccine requires the ability to generate immune responses in the genital tract. In order for this work to progress we must define the best technique for generating genital tract immunity. The reproductive physiology and anatomy of rhesus macaques is remarkably similar to humans. Little work has been done to define the normal immune system of the genital tract in women and nonhuman primates. It is clear that local immune responses to vaginally administered antigens occur in women and rhesus macaques and that the cellular components of a local immune system are present in the lower genital tract of both women and rhesus macaques. Recently, we have made considerable advances in the understanding of female genital tract immunology by studying the rhesus macaque. The techniques and assays in our laboratory can be easily adapted to assist in the effort to elicit strong immunity to a contraceptive vaccine. In the proposed studies, the antigens we will use for immunization will include irrelevant antigens such as tetanus toxoid and cholera toxin, and relevant antigens such as the sperm surface protein PH-20. The irrelevant antigens will be used because we have extensive experience with the immune response of monkeys to these antigens and they will serve as a useful baseline to gauge immune responses to PH-20. In addition, we will use other antigens which could prove to be useful as contraceptive vaccines as they are developed by other members of this Center. Experiments with contraceptive vaccines based on sperm antigens have demonstrated that it can be straightforward to produce effective immunity in rodents. However, current studies in nonhuman primates have resulted in only moderate immune responses to the same antigens. A major goal of this project is to determine if the timing of immunization in relation to the menstrual cycle affects genital tract immune responses in rhesus macaques. Further, we will determine if administration of exogenous steroid hormones can strengthen and direct the immune response to mucosal sites. The overall goal of this project is to develop novel immunization strategies designed to produce strong immune responses in the genital tract of nonhuman primates.