IMMUNOGENICITY OF MULTIPLE ANTIGEN PEPTIDES (MAP) CONTAINING T-CELL AND B-CELL EPITOPES OF THE REPEAT REGION OF THE PLASMODIUM-FALCIPARUM CIRCUMSPOROZOITE PROTEIN

被引:70
作者
MUNESINGHE, DY
CLAVIJO, P
CALLE, MC
NUSSENZWEIG, RS
NARDIN, E [1 ]
机构
[1] NYU, SCH MED, DEPT MED & MOLEC PARASITOL, NEW YORK, NY 10010 USA
[2] UNIV COLOMBO, DEPT ZOOL, COLOMBO, SRI LANKA
关键词
D O I
10.1002/eji.1830211217
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The immunogenicity of multiple antigen peptides (MAP) constructs containing T and B cell epitopes of the repeat region of the P. falciparum circumsporozoite (CS) protein was examined in vitro, using a human T cell clone, and in vivo, using four different strains of mice. All the MAP constructs that contained the T cell epitope, (DPNANPNVDPNANPNV), stimulated proliferation and interferon-gamma production by a human T cell clone specific for this epitope which is located in the 5' end of the repeat region of the P. falciparum CS protein. These human T cells did not recognize MAP that contained only the B cell epitope, (NANP)3, which is located in the 3' repeat region. Optimal antibody responses were obtained in mice immunized with MAP containing four copies of tandemly arranged T and B cell epitopes, (TB)4. The murine immune response to the MAP constructs was genetically restricted. Mice of a high responder strain, C57BL, recognized both the 5' and 3' repeat sequences in the MAP as T, as well as B, cell epitopes and developed very high anti-MAP and anti-sporozoite antibody titers. A/J and C3H mice, which were intermediate responders, developed lower antibody titers which varied according to the orientation of the T vs. the B cell epitopes within the MAP constructs. BALB/c mice were nonresponders and did not develop antibodies following immunization with any of the MAP constructs containing the 5' and 3' repeats of the P. falciparum CS protein.
引用
收藏
页码:3015 / 3020
页数:6
相关论文
共 17 条
  • [1] THE CIRCUMSPOROZOITE PROTEIN GENE FROM NF54, A PLASMODIUM-FALCIPARUM ISOLATE USED IN MALARIA VACCINE TRIALS
    CASPERS, P
    GENTZ, R
    MATILE, H
    PINK, JR
    SINIGAGLIA, F
    [J]. MOLECULAR AND BIOCHEMICAL PARASITOLOGY, 1989, 35 (02) : 185 - 190
  • [2] DELGIUDICE G, 1986, J IMMUNOL, V137, P2952
  • [3] A MULTIPLE ANTIGEN PEPTIDE FROM THE REPETITIVE SEQUENCE OF THE PLASMODIUM-MALARIAE CIRCUMSPOROZOITE PROTEIN INDUCES A SPECIFIC ANTIBODY-RESPONSE IN MICE OF VARIOUS H-2 HAPLOTYPES
    DELGIUDICE, G
    TOUGNE, C
    LOUIS, JA
    LAMBERT, PH
    BIANCHI, E
    BONELLI, F
    CHIAPPINELLI, L
    PESSI, A
    [J]. EUROPEAN JOURNAL OF IMMUNOLOGY, 1990, 20 (07) : 1619 - 1622
  • [4] GENETIC-CONTROL OF THE IMMUNE-RESPONSE IN MICE TO A PLASMODIUM-FALCIPARUM SPOROZOITE VACCINE - WIDESPREAD NONRESPONSIVENESS TO SINGLE MALARIA T-EPITOPE IN HIGHLY REPETITIVE VACCINE
    GOOD, MF
    BERZOFSKY, JA
    MALOY, WL
    HAYASHI, Y
    FUJII, N
    HOCKMEYER, WT
    MILLER, LH
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1986, 164 (02) : 655 - 660
  • [5] HUMAN T-CELL RECOGNITION OF THE CIRCUMSPOROZOITE PROTEIN OF PLASMODIUM-FALCIPARUM - IMMUNODOMINANT T-CELL DOMAINS MAP TO THE POLYMORPHIC REGIONS OF THE MOLECULE
    GOOD, MF
    POMBO, D
    QUAKYI, IA
    RILEY, EM
    HOUGHTEN, RA
    MENON, A
    ALLING, DW
    BERZOFSKY, JA
    MILLER, LH
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1988, 85 (04) : 1199 - 1203
  • [6] SAFETY AND IMMUNOGENICITY IN MAN OF A SYNTHETIC PEPTIDE MALARIA VACCINE AGAINST PLASMODIUM-FALCIPARUM SPOROZOITES
    HERRINGTON, DA
    CLYDE, DF
    LOSONSKY, G
    CORTESIA, M
    MURPHY, JR
    DAVIS, J
    BAQAR, S
    FELIX, AM
    HEIMER, EP
    GILLESSEN, D
    NARDIN, E
    NUSSENZWEIG, RS
    NUSSENZWEIG, V
    HOLLINGDALE, MR
    LEVINE, MM
    [J]. NATURE, 1987, 328 (6127) : 257 - 259
  • [7] STRAIN VARIATION IN THE CIRCUMSPOROZOITE PROTEIN GENE OF PLASMODIUM-FALCIPARUM
    LOCKYER, MJ
    SCHWARZ, RT
    [J]. MOLECULAR AND BIOCHEMICAL PARASITOLOGY, 1987, 22 (01) : 101 - 108
  • [8] CONSERVED REPETITIVE EPITOPE RECOGNIZED BY CD4+ CLONES FROM A MALARIA-IMMUNIZED VOLUNTEER
    NARDIN, EH
    HERRINGTON, DA
    DAVIS, J
    LEVINE, M
    STUBER, D
    TAKACS, B
    CASPERS, P
    BARR, P
    ALTSZULER, R
    CLAVIJO, P
    NUSSENZWEIG, RS
    [J]. SCIENCE, 1989, 246 (4937) : 1603 - 1607
  • [9] RATIONALE FOR THE DEVELOPMENT OF AN ENGINEERED SPOROZOITE MALARIA VACCINE
    NUSSENZWEIG, V
    NUSSENZWEIG, RS
    [J]. ADVANCES IN IMMUNOLOGY, 1989, 45 : 283 - 334
  • [10] SCHUMACHER JH, 1988, J IMMUNOL, V141, P1576