EFFECTS OF THE ESTROUS-CYCLE ON LOCAL HUMORAL IMMUNE-RESPONSES AND PROTECTION OF INTRANASALLY IMMUNIZED FEMALE MICE AGAINST HERPES-SIMPLEX VIRUS TYPE-2 INFECTION IN THE GENITAL-TRACT

This study demonstrates that the levels of gB-specific IgG and IgA in vaginal washes of mice immunized intranasally (i.n.) with a recombinan t adenovirus vector expressing herpes simplex virus (HSV) glycoprotein B (AdgB8) vary inversely with each other and are dependent on the sta ge of the estrous cycle. Anti-gB IgA titers in vaginal washes were sig nificantly higher during estrus than diestrus or proestrus, whereas sp ecific IgG titers were significantly higher during diestrus than estru s. This was further demonstrated in hormone-treated mice, where proges terone administration induced a diestrus-like state that resulted in e levated specific IgG-to-IgA ratios. Interestingly, unimmunized mice we re only susceptible to intravaginal (ivag) infection with HSV-2 during diestrus. Mice immunized i.n. with AdgB8 and given progesterone were protected from a lethal intravaginal HSV-2 challenge, despite the fact that virus replication was present for 4 days postchallenge. Further, high numbers of gB-specific IgA and IgG antibody-secreting cells were present in both the genital tracts and the draining iliac lymph nodes of i.n.-immunized, but not unimmunized, mice 6 days following ivag HS V-2 challenge. These results demonstrate that the levels of specific a ntibodies in the female genital tract are dependent on the stage of th e estrous cycle. Furthermore, i.n. AdgB8 immunization provided a signi ficant level of protection and specific IgA and IgG antibody-secreting cells in the genital tissues during resolution of an ivag infection w ith HSV-2. (C) 1996 Academic Press, Inc.