Induction of HIV-specific cytotoxic T lymphocytes in vivo with hybrid HIV-1 V3:Ty-virus-like particles.
In general, it has proven difficult to induce CTL responses using simple proteins or peptides without resorting to specialized adjuvants. In this study we show that particulate polymeric Ag in the form of hybrid Ty virus-like particles carrying the V3 region of HIV-1 gp120/160 envelope protein (V3:Ty-VLP) induce V3-specific CTL in BALB/c mice in the absence of adjuvant or lipid vehicle. In vitro restimulation of splenocytes with V3 peptide was necessary in order to generate effector CTL. Th cell activation was not required for this in vitro restimulation phase. The CTL induced by the V3:Ty-VLP were CD8+ve, H-2d-restricted, and HIV-1 isolate-specific (IIIB or MN). Co-administration of IIIB V3:Ty-VLP and MN V3:Ty-VLP primed both IIIB and MN V3-specific CTL. However, only IIIB V3-specific CTL were primed by hybrid Ty-VLP carrying IIIB, MN, and RF V3 loop sequences on the same particle indicating that there is intra- but not intermolecular competition between CTL epitopes. In direct comparisons, V3:Ty-VLP were substantially more potent than rgp120. Rgp160 and a 40mer IIIB V3 peptide both failed to prime V3-specific CTL. These data suggest that the particulate nature of hybrid Ty-VLP facilitates uptake into APC with subsequent access to the MHC class I processing pathway and that they may be useful vaccine vehicles for inducing cytolytic immunity against HIV-1 and other intracellular pathogens.
Layton
G T
GT
British Bio-technology Ltd., Cowley, Oxford, U.K.
Harris
S J
SJ
Gearing
A J
AJ
Hill-Perkins
M
M
Cole
J S
JS
Griffiths
J C
JC
Burns
N R
NR
Kingsman
A J
AJ
Adams
S E
SE
D000595:Amino Acid Sequence; D000818:Animals; D016827:CD8 Antigens / Q000032:analysis; D005260:Female; D006183:H-2 Antigens / Q000502:physiology; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D016827:CD8 Antigens; D006183:H-2 Antigens; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins