The effects of adjuvants on CTL induction by V3:Ty-virus-like particles (V3-VLPs) in mice

被引:12
作者
Harris, SJ [1 ]
Woodrow, SA [1 ]
Gearing, AJH [1 ]
Adams, SE [1 ]
Kingsman, AJ [1 ]
Layton, GT [1 ]
机构
[1] UNIV OXFORD, DEPT BIOCHEM, VIRUS MOL BIOL GRP, OXFORD OX1 3QU, ENGLAND
关键词
adjuvants; virus-like particles; cytotoxic T-lymphocyte; HIV-1; V3;
D O I
10.1016/0264-410X(96)00010-2
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
We have previously described the generation of HIV-1 V3-specific cytotoxic T-lymphocytes (CTL) responses in BALB/c (H-2(d)) mice following immunization with Ty-virus-like particles carrying the V3 loop of gp120 (V3-VLPs) without adjuvant. In this study the effects of various adjuvants on CTL induction by V3-VLPs was examined Mice immunized with V3-VLPs formulated in aqueous-based adjuvants, Deter, gamma-inulin, galactosaminylmuramyl dipeptide and Chemivax generated V3-specific CTL responses, although at reduced levels when compared to the no adjuvant group. V3-VLPs prepared in Alhydrogel, algamulin or as an oil emulsion in SAF-MF failed to generate V3-specific CTL responses. The mechanism whereby alum prevented the induction of a CTL response was investigated further. Immunization with V3-VLPs prepared in non-saturating doses of alum or alum plus EDTA primed for strong CTL responses, indicating that free VLPs do, but alum-bound VLPs do not enter the MHC class I processing pathway of antigen-presenting cells (APCs). Furthermore, V3-VLPs with very low doses of alum led to an enhancement of the CTL response. The formulation of hybrid Ty-VLPs in oil based or precipitating adjuvants, therefore, inhibits access to the MHC class I processing pathway of APCs. The intact particulate structure of hybrid VLPs is therefore strictly necessary for CTL induction. Copyright (C) 1996 Elsevier Science Ltd.
引用
收藏
页码:971 / 976
页数:6
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