THE EFFECTS OF ADJUVANTS ON CTL INDUCTION BY V3-TY-VIRUS-LIKE PARTICLES (V3-VLPS) IN MICE

We have previously described the generation of HIV-1 V3-specific cytot oxic T-lymphocytes (CTL) responses in BALB/c (H-2(d)) mice following i mmunization with Ty-virus-like particles carrying the V3 loop of gp120 (V3-VLPs) without adjuvant. In this study the effects of various adju vants on CTL induction by V3-VLPs was examined Mice immunized with V3- VLPs formulated in aqueous-based adjuvants, Deter, gamma-inulin, galac tosaminylmuramyl dipeptide and Chemivax generated V3-specific CTL resp onses, although at reduced levels when compared to the no adjuvant gro up. V3-VLPs prepared in Alhydrogel, algamulin or as an oil emulsion in SAF-MF failed to generate V3-specific CTL responses. The mechanism wh ereby 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 th at free VLPs do, but alum-bound VLPs do not enter the MHC class I proc essing pathway of antigen-presenting cells (APCs). Furthermore, V3-VLP s with very low doses of alum led to an enhancement of the CTL respons e. The formulation of hybrid Ty-VLPs in oil based or precipitating adj uvants, therefore, inhibits access to the MHC class I processing pathw ay of APCs. The intact particulate structure of hybrid VLPs is therefo re strictly necessary for CTL induction. Copyright (C) 1996 Elsevier S cience Ltd.