INFECTION OF MONKEYS BY INTRAVAGINAL INOCULATION OF SIV

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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