INFECTION OF MONKEYS BY INTRAVAGINAL INOCULATION OF SIV

我们一直在同步猴子的月经周期， 孕酮治疗，以使所有的猴子在一个特定的 在周期的同一阶段进行阴道接种实验， 在无创伤性SIV接种时， 插入阴道 在月经周期的孕酮阶段， pH值可能不那么酸，阴道上皮最薄， 有助于延长病毒存活时间， 粘膜。 为了同步循环，我们观察猴子 月经出血，并开始每日注射黄体酮16天 在出血的第一个迹象之后，这对应于 排卵 因为猴子们并不是同时进入月经期 时间，第一只开始月经的猴子可以在 孕激素治疗多达40天或更长的时间前，最后一次 猴子进入月经期，猴子的月经持续时间各不相同。 孕酮治疗 因此，一旦所有的猴子 孕酮10天后我们就停止治疗 后4天内 停止注射黄体酮所有的猴子开始月经。 月经开始后16天，我们再次开始每天注射 孕酮 经过至少10天的黄体酮治疗， 阴道内注射。 因此所有的猴子都是同步的 她们的月经周期都在接受黄体酮治疗， 在最后一次月经后的相同天数 接种。 在我们最初的实验中，11例中有9例 猴子在一次阴道内接种后就被感染了。 这 去年，我们比较了孕酮同步的猴子， 经阴道滴注安慰剂凝胶预处理的猴 没有接受过安慰剂治疗。 接受治疗的3只猴中有2只 与3/3没有服用安慰剂的猴子相比， 治疗。 在这一点上，我们的NIH项目官员要求我们尝试 没有接受孕酮治疗的猕猴。 我们 给5只没有接受孕酮的猴子接种相同的 成功感染同步化猴子的SIV原种， 没有人被感染。 然后我们沿着再次接种这5只猴子 用4只不同SIV储备的幼稚猴子， 体外效价较高。 同样，没有一只猴子被感染。 这并不令人惊讶，因为其他人最近发表了， 接受长效避孕激素的猴子 比正常猴子更容易感染阴道炎 基于这些 结果，我们将集中我们未来的努力， 阴道接种模型，

We have been synchronizing the menstrual cycle of monkeys by progesterone treatments in order to have all monkeys in a particular vaginal inoculation experiment at the same stage of the cycle and under progesterone influence at the time of atraumatic SIV inoculation into the vagina. In the progesterone phase of the cycle the vaginal pH may be less acid and the vaginal epithelium is thinnest, which may be conducive to longer virus survival and successful infection across the mucosa. To synchronize the cycle, we observe the monkeys for menstrual bleeding, and begin daily progesterone injections 16 days after the first sign of bleeding, which corresponds to the time of ovulation. Since the monkeys do not all enter menses at the same time, the first monkey to begin menses may be initiated on progesterone treatment as many as 40 or more days before the last monkey enters menses, and the monkeys vary regarding the duration of progesterone treatment. Therefore, once all monkeys have been on progesterone for 10 days, we stop the treatments. Within 4 days after stopping progesterone injections all the monkeys begin menses. Sixteen days after menses begin we again start daily injections of progesterone. After at least 10 days of progesterone treatments we inoculate SIV intravaginally. Thus all monkeys are synchronized in their menstrual cycles and all have been on progesterone treatment for the same number of days after their last menses at the time of inoculation. In our inital experiments with this procedure, 9 of 11 monkeys became infected after a single intravaginal inoculation. This past year we compared progesterone synchronized monkeys which had been pretreated with an intravaginal instillation of placebo gel to monkeys which had not been treated with the placebo. Two of 3 monkeys treated with the placebo became infected versus 3/3 monkeys not placebo treated. At this point, our NIH project officer requested that we try inoculating monkeys which had received no progesterone treatment. We inoculated 5 monkeys that had received no progesterone with the same SIV stock that had successfully infected the synchronized monkeys and none became infected. We then inoculated again these 5 monkeys along with 4 naive monkeys with a different SIV stock that had a 10-fold higher titer in vitro. Again, none of the monkeys became infected. This was not too surprising since others have published recently that monkeys which have received depot contraceptive hormones are much more susceptible to vaginal infection than normal monkeys. Based on these results, we will concentrate our future efforts on standardizing a vaginal inoculation model using