Long-term multiepitopic cytotoxic-T-lymphocyte responses induced in chimpanzees by combinations of Plasmodium falciparum liver-stage peptides and lipopeptides

被引:42
作者
BenMohamed, L
Thomas, A
Druilhe, P
机构
[1] Inst Pasteur, Unite Parasitol Biomed, F-75015 Paris, France
[2] Univ Calif Irvine, Coll Med, Dept Ophthalmol, Lab Cellular & Mol Immunol, Irvine, CA 92697 USA
[3] Univ Calif Irvine, Ctr Immunol, Irvine, CA 92697 USA
[4] Biomed Primate Res Ctr, NL-2280 GH Rijswijk, Netherlands
关键词
D O I
10.1128/IAI.72.8.4376-4384.2004
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Preclinical immunogenicity studies of 12 malaria peptides, selected from four Plasmodium falciparum antigens (Ags), namely, LSA1, LSA3, SALSA, and STARP, that are expressed at the pre-erythrocytic (sporozoite and liver) stages of the human parasite were carried out in chimpanzees. To strengthen their immunogenicity, six of these synthetic peptides were modified by the C-terminal addition of a single palmitoyl chain (lipopeptides) and delivered without adjuvant, whereas the remaining six unmodified peptides were emulsified and delivered by using Montanide ISA51 adjuvant. We have previously reported that these peptides and lipopeptides induce high B-cell and CD4(+)-T-helper responses in chimpanzees. In this report, we show their ability to induce multiepitopic and long-lasting antigen-specific CD8(+) cytotoxic-T-lymphocyte (CTL) responses. The magnitude, consistency, and memory of CTL responses generated by LSA3 peptides point to the strong immunogenicity of this liver-stage Ag. These findings support the screening strategy used to select the four P. falciparum pre-erythrocytic Ags and emphasize their valuable immunogenic properties. The successful immunization of nonhuman primates with combinations of corresponding peptides in a mineral oil emulsion (ISA51) and lipopeptides in saline provide a vaccine formulation that can be tested in humans.
引用
收藏
页码:4376 / 4384
页数:9
相关论文
共 72 条
  • [1] IDENTIFICATION OF CONSERVED ANTIGENIC COMPONENTS FOR A CYTOTOXIC T-LYMPHOCYTE-INDUCING VACCINE AGAINST MALARIA
    AIDOO, M
    LALVANI, A
    ALLSOPP, CEM
    PLEBANSKI, M
    MEISNER, SJ
    KRAUSA, P
    BROWNING, M
    MORRISJONES, S
    GOTCH, F
    FIDOCK, DA
    TAKIGUCHI, M
    ROBSON, KJH
    GREENWOOD, BM
    DRUILHE, P
    WHITTLE, HC
    HILL, AVS
    [J]. LANCET, 1995, 345 (8956) : 1003 - 1007
  • [2] Cytotoxic T-lymphocyte epitopes for HLA-B53 and other HLA types in the malaria vaccine candidate liver-stage antigen 3
    Aidoo, M
    Lalvani, A
    Gilbert, SC
    Hu, JT
    Daubersies, P
    Hurt, N
    Whittle, HC
    Druihle, P
    Hill, AVS
    [J]. INFECTION AND IMMUNITY, 2000, 68 (01) : 227 - 232
  • [3] A decaepitope polypeptide primes for multiple CD8+ IFN-γ and Th lymphocyte responses:: Evaluation of multiepitope polypeptides as a mode for vaccine delivery
    Alexander, J
    Oseroff, C
    Dahlberg, C
    Qin, MS
    Ishioka, G
    Beebe, M
    Fikes, J
    Newman, M
    Chesnut, RW
    Morton, PA
    Fok, K
    Appella, E
    Sette, A
    [J]. JOURNAL OF IMMUNOLOGY, 2002, 168 (12) : 6189 - 6198
  • [4] Andrieu M, 2000, EUR J IMMUNOL, V30, P3256, DOI 10.1002/1521-4141(200011)30:11<3256::AID-IMMU3256>3.0.CO
  • [5] 2-H
  • [6] Two human immunodeficiency virus vaccinal lipopeptides follow different cross-presentation pathways in human dendritic cells
    Andrieu, M
    Desoutter, JF
    Loing, E
    Gaston, J
    Hanau, D
    Guillet, JG
    Hosmalin, A
    [J]. JOURNAL OF VIROLOGY, 2003, 77 (02) : 1564 - 1570
  • [7] Protective T cell immunity against malaria liver stage after vaccination with live sporozoites under chloroquine treatment
    Belnoue, E
    Costa, FTM
    Frankenberg, T
    Vigário, AM
    Voza, T
    Leroy, N
    Rodrigues, MM
    Landau, I
    Snounou, G
    Rénia, L
    [J]. JOURNAL OF IMMUNOLOGY, 2004, 172 (04) : 2487 - 2495
  • [8] High immunogenicity in chimpanzees of peptides and lipopeptides derived from four new Plasmodium falciparum pre-erythrocytic molecules
    Benmohamed, L
    Thomas, A
    Bossus, M
    Brahimi, K
    Wubben, J
    Gras-Masse, H
    Druilhe, P
    [J]. VACCINE, 2000, 18 (25) : 2843 - 2855
  • [9] Induction of CTL response by a minimal epitope vaccine in HLA A*0201/DR1 transgenic mice:: Dependence on HLA class II restricted TH response
    BenMohamed, L
    Krishnan, R
    Longmate, J
    Auge, C
    Low, L
    Primus, J
    Diamond, DJ
    [J]. HUMAN IMMUNOLOGY, 2000, 61 (08) : 764 - 779
  • [10] Identification of novel immunodominant CD4+ Th1-type T-cell peptide epitopes from herpes simplex virus glycoprotein D that confer protective immunity
    BenMohamed, L
    Bertrand, G
    McNamara, CD
    Gras-Masse, H
    Hammer, J
    Wechsler, SL
    Nesburn, AB
    [J]. JOURNAL OF VIROLOGY, 2003, 77 (17) : 9463 - 9473