Immunization with a soluble recombinant HIV protein entrapped in biodegradable microparticles induces HIV-specific CD8(+) cytotoxic T lymphocytes and CD4(+) Th1 cells

被引:128
作者
Moore, A
McGuirk, P
Adams, S
Jones, WC
McGee, JP
OHagan, DT
Mills, KHG
机构
[1] NATL INST BIOL STAND & CONTROLS, DEPT IMMUNOBIOL, POTTERS BAR EN6 3QG, HERTS, ENGLAND
[2] UNIV NOTTINGHAM, DEPT PHARMACEUT SCI, NOTTINGHAM NG7 2RD, ENGLAND
关键词
biodegradable microparticle; cytotoxic T lymphocyte; Th1; cell; HIV; vaccine delivery; recombinant vaccine;
D O I
10.1016/0264-410X(95)00184-3
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
One of the major obstacles to the development of successful recombinant vaccines against human immunoodeficiency virus (HIV) and other intracellular pathogens is the identification of a safe and effective vaccine delivery system for the induction of cell mediated immunity with soluble protein antigens. In this study it was demonstrated that immunization with a recombinant HIV envelope (env) protein entrapped in biodegradable poly (lactide-co-glycolide) (PLG) microparticles induced consistent HIV-specific CD4(+) and CD8(+) T-cell responses in mice. Major histocompatibility complex (MHC) class I-restricted cytotoxic T lymphocytes (CTL) responses were detected following a single systemic immunization with gp120 entrapped microparticles and when given by the intranasal (in.) route induced HIV-specific CD8(+) CTL and secretory IgA, Furthermore immunization with gp120 entrapped in microparticles generated CD4(+) T cells that secreted moderate to high levels of IFN-gamma. Therefore, PLG microparticles are a safe and effective means of delivering antigen to the appropriate processing site for the generation of class I-restricted CTL, and ave also capable of inducing Thl cells.
引用
收藏
页码:1741 / 1749
页数:9
相关论文
共 46 条
[41]   INDUCTION OF CD8+ CYTOTOXIC T-CELLS BY IMMUNIZATION WITH PURIFIED HIV-1 ENVELOPE PROTEIN IN ISCOMS [J].
TAKAHASHI, H ;
TAKESHITA, T ;
MOREIN, B ;
PUTNEY, S ;
GERMAIN, RN ;
BERZOFSKY, JA .
NATURE, 1990, 344 (6269) :873-875
[42]   AN IMMUNODOMINANT EPITOPE OF THE HUMAN IMMUNODEFICIENCY VIRUS ENVELOPE GLYCOPROTEIN GP160 RECOGNIZED BY CLASS-I MAJOR HISTOCOMPATIBILITY COMPLEX MOLECULE-RESTRICTED MURINE CYTO-TOXIC LYMPHOCYTES-T [J].
TAKAHASHI, H ;
COHEN, J ;
HOSMALIN, A ;
CEASE, KB ;
HOUGHTEN, R ;
CORNETTE, JL ;
DELISI, C ;
MOSS, B ;
GERMAIN, RN ;
BERZOFSKY, JA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1988, 85 (09) :3105-3109
[43]  
TAYLOR PM, LYMPHOCYTES PRACTICA, P133
[44]  
WEINBERG AD, 1990, J IMMUNOL, V144, P1800
[45]  
WU JY, 1992, J IMMUNOL, V148, P1519
[46]  
ZHOU F, 1992, J IMMUNOL, V149, P1599