This is a multidisciplinary proposal to assess the efficacy of Hormone Immunomodulated Peripheral Vaccination (HIPV), a procedure which allows the induction of common mucosal immunity in naive animals to antigens administered subcutaneously (SQ) or intramuscularly (IM) in conjunction with 1,25 dihydroxyvitamin D3 (1,25(OH)2D3). The proposed studies included evaluation of HIPV with a number of vaccine candidate antigens from selected agents of sexually transmitted disease (STD's) and other mucosal infections. Part of our investigative team has recently shown, using a variety of protein antigen, that peripheral SQ or IM immunization of mice, when accompanied by co-injection or topical application (in the same vicinity) with 1,25(OH)2D3, induces common mucosal immunity (e.g. oropharyngeal, gastrointestinal, and genitourinary IgA and IgG). HIPV also enhances the intensity of humoral IgA, IgM and IgG immune responses to the test antigens. Studies in the present proposal will focus initially on optimizing the HIPV procedure, employing the subunit hepatitis B vaccine as the initial test antigen. During the course of these studies the investigators will also evaluate immunity to four distinct gonococcal protein molecules which may be involved in the molecular pathogenesis of gonococcal salpingitis. These include 1) a liposomal Protein I preparation. 2) a 44kDa, surface-exposed protein that is highly conserved among those Neisseria species pathogenic for humans (i.e. Neisseria gonorrhoeae and Neisseria meningitidis, 3) Protein II, the """"""""opacity"""""""" and epithelial-invasion-associated protein, Opa; and 4) IgA, protease. Finally, the proposed studies will also include analysis of the effectiveness of HIPV in normal animals with a synthetic oligopeptide preparation containing various major outer membrane protein epitopes of Chlamydia trachomatis. For all the antigens tested, animals with no pre-existing systemic or mucosal antibody to the selected protein antigens will be immunized employing HIPV. Lacrimal, oropharyngeal, gastrointestinal, and genitourinary secretions from the immunized animals will be collected at varying intervals post-immunization. When the titer of mucosal antibody is maximal (analyzed by ELISA), selected mucosal secretions will be tested, using gold immunoprobes, for the ability of the mucosal antibodies to combine with their target epitope on viable agents of STD's and to determine if there is uniform distribution of the epitope in the microbial population. HIPV-induced mucosal immunity will also be tested in experimental in vitro models or in experimental animals to determine if the mucosal antibodies induced following HIPV block critical steps in the respective disease processes (e.g., the """"""""damage"""""""" or the """"""""invasion"""""""" phases of the gonococcal interaction with human fallopian tube mucosa). The anti-chlamydial secretions will be tested for their ability to neutralize chlamydial infectivity in vitro in a human cervical epithelial cell model and in vivo in a mouse immunity, and also new STD vaccine candidates (as a prelude to clinical studies with the method and molecule(s) that show the greatest promise). The information gained about inducing a protective mucosal immune response against any one agent of STD's is likely to prove useful in designing strategies for inducing effective mucosal immune response against other agents of STD's (including HIV).
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