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M9490085.TXT
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1994-09-03
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Document 0085
DOCN M9490085
TI Targeted lymph node immunization with simian immunodeficiency virus p27
antigen to elicit genital, rectal, and urinary immune responses in
nonhuman primates.
DT 9411
AU Lehner T; Bergmeier LA; Tao L; Panagiotidi C; Klavinskis LS; Hussain L;
Ward RG; Meyers N; Adams SE; Gearing AJ; et al; Department of
Immunology, United Medical School, Guy's Hospital,; London, United
Kingdom.
SO J Immunol. 1994 Aug 15;153(4):1858-68. Unique Identifier : AIDSLINE
MED/94321795
AB A s.c. route of immunization was developed in non-human primates, which
targets the genitourinary-rectal associated lymphoid tissue. A vaccine
consisting of rSIV gag p27, expressed as hybrid Ty virus-like particles
(p27: Ty-VLP) was administered in the proximity of the internal iliac
lymph nodes. Secretory IgA and IgG Abs to the p27 Ag were elicited in
the vaginal, male urethral, rectal and seminal fluids, urine and serum.
Two or more immunodominant B cell epitopes were identified within
peptides 51-90 and 121-170 of the sequence of p27, using serum or
biliary IgA and IgG Abs. CD4+ T cell proliferative responses to p27 were
elicited predominantly in the targeted internal iliac, as well as the
inferior mesenteric lymph nodes and the spleen, but not in the unrelated
lymph nodes. These cells were then studied for helper function in p27
specific B cell Ab synthesis. Specific IgA and IgG Abs were detected in
the same lymphoid tissues as those that displayed proliferative
responses. However, cross-over reconstitution experiments between
splenic and iliac lymph node B and CD4+ T cells suggest that the iliac B
cells are essential for specific IgA Ab synthesis, whereas splenic B
cells preferentially synthesize IgG Ab. The targeted lymph node (TLN)
route of immunization gave comparable B cell, proliferative T cell, and
Th cell responses to the vaginal, male genitourinary, and rectal mucosal
routes, which were augmented by oral immunization. However, the TLN
route induced urinary and seminal fluid sIgA and IgG Abs in addition to
genital and rectal Abs. Generating secretory IgA and IgG Abs at the
mucosal surfaces, and T and B cell immunity in the regional draining
lymph nodes, spleen and circulation by TLN immunization may prevent
transmission of virus through the mucosa, dissemination of the virus,
and the formation of a latent reservoir of infection.
DE Animal Antibodies, Viral/*IMMUNOLOGY Antigenic Determinants Antigens,
Viral/*IMMUNOLOGY Binding, Competitive Female Gene Products,
gag/*IMMUNOLOGY IgA/IMMUNOLOGY IgG/IMMUNOLOGY Lymph Nodes/*IMMUNOLOGY
Lymphocyte Transformation Lymphoid Tissue/*IMMUNOLOGY Macaca mulatta
Male Rectum/*IMMUNOLOGY Spleen/IMMUNOLOGY Support, Non-U.S. Gov't
SIV/*IMMUNOLOGY T-Lymphocytes, Helper-Inducer/IMMUNOLOGY T4
Lymphocytes/IMMUNOLOGY Urogenital System/*IMMUNOLOGY Vaccines,
Synthetic/ADMINISTRATION & DOSAGE JOURNAL ARTICLE
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).