Potent immunogenic short linear peptide constructs composed of B cell epitopes and Pan DR T Helper Epitopes (PADRE) for antibody responses in vivo

被引:92
作者
delGuercio, MF
Alexander, J
Kubo, RT
Arrhenius, T
Maewal, A
Appella, E
Hoffman, SL
Jones, T
Valmori, D
Sakaguchi, K
Grey, HM
Sette, A
机构
[1] NCI, CELL BIOL LAB, BETHESDA, MD 20892 USA
[2] USN, MED RES INST, MALARIA PROGRAM, ROCKVILLE, MD 20852 USA
[3] LA JOLLA INST ALLERGY & IMMUNOL, LA JOLLA, CA 92037 USA
关键词
short linear peptide; peptide based vaccine; humoral immunity; malaria; PAN DR T helper epitopes;
D O I
10.1016/S0264-410X(97)00186-2
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Induction of humoral immune responses against protein antigen requires that two independent signals be delivered to B cells. It is currently assumed that simple monovalent synthetic peptides would not be effective immunogens for antibody responses because they would not be anticipated to effectively generate the necessary signals unless conjugated to a complex carrier system. In this study, the immunogenicity;of short linear peptide constructs comprising Plasmodium vivax B cell epitopes (PVB) and non-natural Pan-DR T helper cell epitopes (PADRE) was assessed in mice and compared to other types of antigen constructs. The 33-residue PADRE-PVB linear constructs were highly immunogenic and induced responses comparable to those obtained with the multiple antigen peptides (MAP) constructs, both in terms of absolute titers and quality of antibody responses. The anti-PVB antibody responses were of long duration, composed mostly of IgG and reactive with intact sporozoites. The PADRE-PVB constructs were immunogenic when formulated in adjuvants such as Alum and Montanide ISA 51 underlining the relevance of these findings for vaccine development. (C) 1997 Elsevier Science Ltd.
引用
收藏
页码:441 / 448
页数:8
相关论文
共 37 条
  • [1] DEVELOPMENT OF HIGH POTENCY UNIVERSAL DR-RESTRICTED HELPER EPITOPES BY MODIFICATION OF HIGH-AFFINITY DR-BLOCKING PEPTIDES
    ALEXANDER, J
    SIDNEY, J
    SOUTHWOOD, S
    RUPPERT, J
    OSEROFF, C
    MAEWAL, A
    SNOKE, K
    SERRA, HM
    KUBO, RT
    SETTE, A
    GREY, HM
    [J]. IMMUNITY, 1994, 1 (09) : 751 - 761
  • [2] LIPOPOLYSACCHARIDE, LIPID-A, AND LIPOSOMES CONTAINING LIPID-A AS IMMUNOLOGICAL ADJUVANTS
    ALVING, CR
    [J]. IMMUNOBIOLOGY, 1993, 187 (3-5) : 430 - 446
  • [3] LIPOSOMES CONTAINING LIPID-A AS A POTENT NONTOXIC ADJUVANT
    ALVING, CR
    VERMA, JN
    RAO, M
    KRZYCH, U
    AMSELEM, S
    GREEN, SM
    WASSEF, NM
    [J]. RESEARCH IN IMMUNOLOGY, 1992, 143 (02): : 197 - 198
  • [4] BALLOU WR, 1987, LANCET, V1, P1277
  • [5] APPLICATION AND LIMITATIONS OF THE MULTIPLE ANTIGEN PEPTIDE (MAP) SYSTEM IN THE PRODUCTION AND EVALUATION OF ANTIPEPTIDE AND ANTIPROTEIN ANTIBODIES
    BRIAND, JP
    BARIN, C
    VANREGENMORTEL, MHV
    MULLER, S
    [J]. JOURNAL OF IMMUNOLOGICAL METHODS, 1992, 156 (02) : 255 - 265
  • [6] THE RELATION BETWEEN MAJOR HISTOCOMPATIBILITY COMPLEX (MHC) RESTRICTION AND THE CAPACITY OF IA TO BIND IMMUNOGENIC PEPTIDES
    BUUS, S
    SETTE, A
    COLON, SM
    MILES, C
    GREY, HM
    [J]. SCIENCE, 1987, 235 (4794) : 1353 - 1358
  • [7] CALVOCALLE JM, 1993, J IMMUNOL, V150, P1403
  • [8] CAMBIER JC, 1994, ANNU REV IMMUNOL, V12, P457, DOI 10.1146/annurev.immunol.12.1.457
  • [9] CELIS E, 1995, CANC BIOL, V6, P329
  • [10] CHARACTERIZATION OF PLASMODIUM-YOELII MONOCLONAL-ANTIBODIES DIRECTED AGAINST STAGE-SPECIFIC SPOROZOITE ANTIGENS
    CHAROENVIT, Y
    LEEF, MF
    YUAN, LF
    SEDEGAH, M
    BEAUDOIN, RL
    [J]. INFECTION AND IMMUNITY, 1987, 55 (03) : 604 - 608