Vaccine-elicited immune responses prevent clinical AIDS in SHIV89.6P-infected rhesus monkeys

被引:36
作者
Barouch, DH
Fu, TM
Montefiori, DC
Lewis, MG
Shiver, JW
Letvin, NL
机构
[1] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA
[2] Merck Res Labs, West Point, PA 19486 USA
[3] Duke Univ, Med Ctr, Durham, NC 27710 USA
[4] So Res Inst, Frederick, MD 21701 USA
关键词
DNA vaccination; IL-2/Ig; HIV-1; SHIV89.6P;
D O I
10.1016/S0165-2478(01)00266-8
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Accumulating evidence has demonstrated the importance of cytotoxic T lymphocytes (CTLs) and helper T lymphocytes in controlling HIV-1 replication. We have elicited immune responses in rhesus monkeys utilizing DNA vaccines augmented by the administration of IL-2/Ig, a fusion protein consisting of interleukin-2 and the Fc portion of IgG2. These vaccine-elicited immune responses did not prevent infection following a high-dose intravenous challenge with SHIV89.6P but did control viremia to nearly undetectable levels and prevented immunodeficiency and clinical disease. In contrast, control monkeys developed high levels of viremia, and exhibited a rapid loss of CD4(+) T cells, significant clinical disease progression, and death in half of the animals by day 140 following challenge. Vaccine approaches that elicit immune responses capable of reducing plasma viral loads, but not capable of inducing sterilizing immunity, may still provide substantial clinical benefits. (C) 2001 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:57 / 61
页数:5
相关论文
共 25 条
  • [1] Induction of AIDS virus-specific CTL activity in fresh, unstimulated peripheral blood lymphocytes from rhesus macaques vaccinated with a DNA prime/modified vaccinia virus Ankara boost regimen
    Allen, TM
    Vogel, TU
    Fuller, DH
    Mothé, BR
    Steffen, S
    Boyson, JE
    Shipley, T
    Fuller, J
    Hanke, T
    Sette, A
    Altman, JD
    Moss, B
    McMichael, AJ
    Watkins, DI
    [J]. JOURNAL OF IMMUNOLOGY, 2000, 164 (09) : 4968 - 4978
  • [2] Allen TM, 1998, J IMMUNOL, V160, P6062
  • [3] Phenotypic analysis of antigen-specific T lymphocytes
    Altman, JD
    Moss, PAH
    Goulder, PJR
    Barouch, DH
    McHeyzerWilliams, MG
    Bell, JI
    McMichael, AJ
    Davis, MM
    [J]. SCIENCE, 1996, 274 (5284) : 94 - 96
  • [4] Augmentation of immune responses to HIV-1 and simian immunodeficiency virus DNA vaccines by IL-2/Ig plasmid administration in rhesus monkeys
    Barouch, DH
    Craiu, A
    Kuroda, MJ
    Schmitz, JE
    Zheng, XX
    Santra, S
    Frost, JD
    Krivulka, GR
    Lifton, MA
    Crabbs, CL
    Heidecker, G
    Perry, HC
    Davies, ME
    Xie, H
    Nickerson, CE
    Steenbeke, TD
    Lord, CI
    Montefiori, DC
    Strom, TB
    Shiver, JW
    Lewis, MG
    Letvin, NL
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (08) : 4192 - 4197
  • [5] Control of viremia and prevention of clinical AIDS in rhesus monkeys by cytokine-augmented DNA vaccination
    Barouch, DH
    Santra, S
    Schmitz, JE
    Kuroda, MJ
    Fu, TM
    Wagner, W
    Bilska, M
    Craiu, A
    Zheng, XX
    Krivulka, GR
    Beaudry, K
    Lifton, MA
    Nickerson, CE
    Trigona, WL
    Punt, K
    Freed, DC
    Guan, LM
    Dubey, S
    Casimiro, D
    Simon, A
    Davies, ME
    Chastain, M
    Strom, TB
    Gelman, RS
    Montefiori, DC
    Lewis, MG
    Emini, EA
    Shiver, JW
    Letvin, NL
    [J]. SCIENCE, 2000, 290 (5491) : 486 - 492
  • [6] Barouch DH, 1998, J IMMUNOL, V161, P1875
  • [7] Characterization of primary isolate-like variants of simian-human immunodeficiency virus
    Crawford, JM
    Earl, PL
    Moss, B
    Reimann, KA
    Wyand, MS
    Manson, KH
    Bilska, M
    Zhou, JT
    Pauza, CD
    Parren, PWHI
    Burton, DR
    Sodroski, JG
    Letvin, NL
    Montefiori, DC
    [J]. JOURNAL OF VIROLOGY, 1999, 73 (12) : 10199 - 10207
  • [8] Simian immunodeficiency virus (SIV) gag DNA-vaccinated rhesus monkeys develop secondary cytotoxic T-lymphocyte responses and control viral replication after pathogenic SIV infection
    Egan, MA
    Charini, WA
    Kuroda, MJ
    Schmitz, JE
    Racz, P
    Tenner-Racz, K
    Manson, K
    Wyand, M
    Lifton, MA
    Nickerson, CE
    Fu, TM
    Shiver, JW
    Letvin, NL
    [J]. JOURNAL OF VIROLOGY, 2000, 74 (16) : 7485 - 7495
  • [9] Use of major histocompatibility complex class I/peptide/β2M tetramers to quantitate CD8+ cytotoxic T lymphocytes specific for dominant and nondominant viral epitopes in simian-human immunodeficiency virus-infected rhesus monkeys
    Egan, MA
    Kuroda, MJ
    Schmitz, JE
    Charini, WA
    Lord, CI
    Forman, MA
    Letvin, NL
    [J]. JOURNAL OF VIROLOGY, 1999, 73 (07) : 5466 - 5472
  • [10] Effective induction of simian immunodeficiency virus-specific cytotoxic T lymphocytes in macaques by using a multiepitope gene and DNA prime-modified vaccinia virus Ankara boost vaccination regimen
    Hanke, T
    Samuel, RV
    Blanchard, TJ
    Neumann, VC
    Allen, TM
    Boyson, JE
    Sharpe, SA
    Cook, N
    Smith, GL
    Watkins, DI
    Cranage, MP
    McMichael, AJ
    [J]. JOURNAL OF VIROLOGY, 1999, 73 (09) : 7524 - 7532