Humoral and cellular immunities elicited by HIV-1 DNA vaccination

被引:39
作者
Shiver, JW
Davies, ME
Perry, HC
Freed, DC
Liu, MA
机构
[1] Department of Virus and Cell Biology, Merck Research Laboratories, West Point
关键词
D O I
10.1021/js9600991
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Recently it has been shown that immunization with plasmid DNA encoding genes for viral or bacterial antigens can elicit both humoral and cellular immune responses in rodents and nonhuman primates. In this study, mice and nonhuman primates were vaccinated by intramuscular injection with plasmids that express either a secreted form of HIV-1 gp120 or rev proteins. Mice receiving the tPA-gp120 DNA developed antigen-specific antibody responses against recombinant gp120 protein and the V3 peptide neutralization epitope as determined by ELISA. Vaccinated mice also exhibited gp120-specific T cell responses, such as in vitro proliferation of splenocytes and MHC Class I-restricted cytotoxic T lymphocyte (CTL) activities, following antigen restimulation. In addition, supernatants from these lymphocyte cultures showed high levels of gamma-interferon production compared with IL-4, suggesting that primarily type 1-like helper T (Th1) lymphocyte responses were induced by both vaccines. Th1-like responses were also obtained for mice vaccinated with rev DNA. Immune responses induced by gp120 or rev vaccines were dose-dependent, boostable, and long-lived (greater than or equal to 6 months). Nonhuman primates vaccinated with tPA-gp120 DNA also showed antigen-specific T lymphocyte proliferative and humoral responses, including moderate levels of neutralizing sera against homologous HIV. These results suggest that plasmid DNA may provide a powerful means for eliciting humoral and cellular immune responses against HIV.
引用
收藏
页码:1317 / 1324
页数:8
相关论文
共 36 条
  • [1] PROTECTION BY ATTENUATED SIMIAN IMMUNODEFICIENCY VIRUS IN MACAQUES AGAINST CHALLENGE WITH VIRUS-INFECTED CELLS
    ALMOND, N
    KENT, K
    CRANAGE, M
    RUD, E
    CLARKE, B
    STOTT, EJ
    [J]. LANCET, 1995, 345 (8961): : 1342 - 1344
  • [2] BORROW P, 1994, J VIROL, V68, P5103
  • [3] ANTIGENIC IMPLICATIONS OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 ENVELOPE QUATERNARY STRUCTURE - OLIGOMER-SPECIFIC AND OLIGOMER-SENSITIVE MONOCLONAL-ANTIBODIES
    BRODER, CC
    EARL, PL
    LONG, D
    ABEDON, ST
    MOSS, B
    DOMS, RW
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (24) : 11699 - 11703
  • [4] EFFECT OF INTRON-A FROM HUMAN CYTOMEGALOVIRUS (TOWNE) IMMEDIATE-EARLY GENE ON HETEROLOGOUS EXPRESSION IN MAMMALIAN-CELLS
    CHAPMAN, BS
    THAYER, RM
    VINCENT, KA
    HAIGWOOD, NL
    [J]. NUCLEIC ACIDS RESEARCH, 1991, 19 (14) : 3979 - 3986
  • [5] FACILITATED DNA INOCULATION INDUCES ANTI-HIV-1 IMMUNITY IN-VIVO
    CONEY, L
    WANG, B
    UGEN, KE
    BOYER, J
    MCCALLUS, D
    SRIKANTAN, V
    AGADJANYAN, M
    PACHUK, CJ
    HEROLD, K
    MERVA, M
    GILBERT, L
    DENG, KS
    MOELLING, K
    NEWMAN, M
    WILLIAMS, WV
    WEINER, DB
    [J]. VACCINE, 1994, 12 (16) : 1545 - 1550
  • [6] PROTECTIVE EFFECTS OF A LIVE ATTENUATED SIV VACCINE WITH A DELETION IN THE NEF GENE
    DANIEL, MD
    KIRCHHOFF, F
    CZAJAK, SC
    SEHGAL, PK
    DESROSIERS, RC
    [J]. SCIENCE, 1992, 258 (5090) : 1938 - 1941
  • [7] PRECLINICAL EFFICACY OF A PROTOTYPE DNA VACCINE - ENHANCED PROTECTION AGAINST ANTIGENIC DRIFT IN INFLUENZA-VIRUS
    DONNELLY, JJ
    FRIEDMAN, A
    MARTINEZ, D
    MONTGOMERY, DL
    SHIVER, JW
    MOTZEL, SL
    ULMER, JB
    LIU, MA
    [J]. NATURE MEDICINE, 1995, 1 (06) : 583 - 587
  • [8] A QUALITATIVE PROGRESSION IN HIV TYPE-1 GLYCOPROTEIN-120-SPECIFIC CYTOTOXIC CELLULAR AND HUMORAL IMMUNE-RESPONSES IN MICE RECEIVING A DNA-BASED GLYCOPROTEIN-120 VACCINE
    FULLER, DH
    HAYNES, JR
    [J]. AIDS RESEARCH AND HUMAN RETROVIRUSES, 1994, 10 (11) : 1433 - 1441
  • [9] DNA VACCINES - PROTECTIVE IMMUNIZATIONS BY PARENTERAL, MUCOSAL, AND GENE-GUN INOCULATIONS
    FYNAN, EF
    WEBSTER, RG
    FULLER, DH
    HAYNES, JR
    SANTORO, JC
    ROBINSON, HL
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (24) : 11478 - 11482
  • [10] DIRECT GENE-TRANSFER INTO NONHUMAN PRIMATE MYOFIBERS INVIVO
    JIAO, SS
    WILLIAMS, P
    BERG, RK
    HODGEMAN, BA
    LIU, LJ
    REPETTO, G
    WOLFF, JA
    [J]. HUMAN GENE THERAPY, 1992, 3 (01) : 21 - 33