       Document 0204
 DOCN  M9440204
 TI    Mucosal model of genital immunization in male rhesus macaques with a
       recombinant simian immunodeficiency virus p27 antigen.
 DT    9404
 AU    Lehner T; Tao L; Panagiotidi C; Klavinskis LS; Brookes R; Hussain L;
       Meyers N; Adams SE; Gearing AJ; Bergmeier LA; Division of Immunology,
       United Medical School, Guy's Hospital,; London, United Kingdom.
 SO    J Virol. 1994 Mar;68(3):1624-32. Unique Identifier : AIDSLINE
       MED/94149853
 AB    Human immunodeficiency virus (HIV) can be transmitted through infected
       seminal fluid or vaginal or rectal secretions during heterosexual or
       homosexual intercourse. To prevent mucosal transmission and spread to
       the regional lymph nodes, an effective vaccine may need to stimulate
       immune responses at the genitourinary mucosa. In this study, we have
       developed a mucosal model of genital immunization in male rhesus
       macaques, by topical urethral immunization with recombinant simian
       immunodeficiency virus p27gag, expressed as a hybrid Ty virus-like
       particle (Ty-VLP) and covalently linked to cholera toxin B subunit. This
       treatment was augmented by oral immunization with the same vaccine but
       with added killed cholera vibrios. Polymeric secretory immunoglobulin A
       (sIgA) and IgG antibodies to p27 were induced in urethral secretions,
       urine, and seminal fluid. This raises the possibility that the
       antibodies may function as a primary mucosal defense barrier against SIV
       (HIV) infection. The regional lymph nodes which constitute the
       genital-associated lymphoid tissue contained p27-specific CD4+
       proliferative and helper T cells for antibody synthesis by B cells,
       which may function as a secondary immune barrier to infection. Blood and
       splenic lymphocytes also showed p27-sensitized CD4+ T cells and B cells
       in addition to serum IgG and IgA p27-specific antibodies; this
       constitutes a third level of immunity against dissemination of the
       virus. A comparison of genito-oral with recto-oral and intramuscular
       routes of immunization suggests that only genito-oral immunization
       elicits specific sIgA and IgG antibodies in the urine, urethra, and
       seminal fluid. Both genito-oral and recto-oral immunizations induced
       T-cell and B-cell immune responses in regional lymph nodes, with
       preferential IgA antibody synthesis. The mucosal route of immunization
       may prevent not only virus transmission through the genital mucosa but
       also dissemination and latency of the virus in the draining lymph nodes.
 DE    Animal  Antibodies, Viral/*BIOSYNTHESIS/BLOOD/URINE  Antigens,
       Viral/*IMMUNOLOGY  B-Lymphocytes/IMMUNOLOGY  Comparative Study  Drug
       Administration Routes  Epithelium/IMMUNOLOGY  Genitalia,
       Male/*IMMUNOLOGY  IgA/BLOOD/URINE  IgG/BLOOD/URINE  Immunization,
       Secondary  Lymph Nodes/IMMUNOLOGY  Macaca mulatta  Male  Models,
       Biological  Rectum/IMMUNOLOGY  Seminal Vesicles/IMMUNOLOGY/SECRETION
       Simian Acquired Immunodeficiency Syndrome/*PREVENTION & CONTROL
       Spleen/IMMUNOLOGY  Support, Non-U.S. Gov't  T-Lymphocytes/IMMUNOLOGY
       T-Lymphocytes, Helper-Inducer  *Vaccination  Vaccines,
       Synthetic/ADMINISTRATION & DOSAGE/*THERAPEUTIC USE  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

