Residence half-life of IgG administered topically to the mouse vagina

Abstract

Antibodies delivered directly to the vagina can provide passive immunoprotection against pregnancy and sexually transmitted disease. The duration of protection is limited by the residence time of the antibodies in the vagina; to our knowledge such residence times have not been reported. We investigated the time-course of disappearance of IgG delivered to the mouse vagina using three different methods to monitor the amount of administered IgG remaining in the vagina: gamma counting of 125I-IgG, viral neutralization of unlabeled monoclonal anti-herpes virus IgG2a, and ELISA of biotinylated IgG. The test IgG was delivered to the vagina in saline and recovered by lavage. All three methods yielded similar results, suggesting that the residence half-life is not significantly affected by the volume administered, phase of the estrous cycle, or labeling of IgG. In awake mice, a significant fraction of IgG disappeared with a relatively short half-life, (t1/2)alpha, of 0.7 +/- 0.1 h; but this rapid (alpha phase) decrease did not occur in anesthetized mice, suggesting that the movements of awake mice expel some of the test IgG-saline solution from the vagina. Over the next 25 h, the test IgG disappeared with a residence half-life, (t1/2)beta, of 5 +/- 2 h. We believe this slow elimination of IgG may depend on the rate that mucus secretions are shed from the vagina.

Functional Characterization of Antibodies against Neisseria gonorrhoeae Opacity Protein Loops

“…It is possible, however, that technical limitations may have prevented us from detecting a protective effect. The concentration of antibodies may not have been high enough and similar to that reported by Sherwood et al [50], antibodies were gradually lost within 24 hrs post-inoculation. Clearance via opsonophagocytosis might not occur during this time frame since phagocytes are not detected in infected murine tissue until 2 to 5 days post-inoculation [38].…”

Intranasal Immunization with Gonococcal Outer Membrane Preparations Reduces the Duration of Vaginal Colonization of Mice byNeisseria gonorrhoeae

“…The reliability of a murine model to predict the success of a gonorrhea vaccine in humans may be hindered by the absence of certain human-specific adherence receptors, such as the CD46 gonococcal pilus receptor [37] and the CD66 family of Opa protein receptors [38]. However, it is likely that gonococci do adhere to the vaginal mucosa in the model we describe, because their ability to exist for prolonged periods of time in this environment suggests that they have a mechanism to resist clearance by constant shedding of vaginal mucus [39]. Indeed, epithelial cell-associated gonococci were seen in stained smears from infected mice.…”

Transferrin conjugation confers mucosal molecular targeting to a model HIV-1 trimeric gp140 vaccine antigen

“…For example, intravaginal vaccination studies utilizing Toll-like receptor (TLR) agonists and CD4 + T helper epitopes [7] or powerful adjuvants such as cholera toxin [8] have demonstrated that immunization at this mucosal surface is possible but responses elicited to unadjuvanted vaccine antigens, where vaginal epithelial barrier integrity is maintained, have been modest [9,10]. This may be due to a number of reasons, distinct from the recruitment and activation of immune responsive cells, such as the inability of vaccinating antigens to traverse the type II stratified squamous epithelial barrier characteristic of the lower female reproductive tract [11], the possibility that the female reproductive tract is directed more towards an induced state of tolerance rather than inflammation [12], vaginal leakage of the applied antigen [13] or sequestration and elimination of the antigen by locally produced mucus and proteases [14,15]. For human immunodeficiency virus (HIV) there is the additional concern that vaccine/adjuvant-induced local inflammation may fuel infection through the recruitment of target cells as suggested by a recent clinical trial.…”