A minimally replicative HIV-2 live-virus vaccine protects M-nemestrina from disease after HIV-2287 challenge

被引:27
作者
Looney, DJ
McClure, J
Kent, SJ
Radaelli, A
Kraus, G
Schmidt, A
Steffy, K
Greenberg, P
Hu, SL
Morton, WR
Wong-Staal, F
机构
[1] VA San Diego Healthcare Syst, San Diego, CA 92161 USA
[2] Univ Calif San Diego, Dept Med 0678, La Jolla, CA 92093 USA
[3] Univ Milan, Dept Pharmacol, Inst Pharmacol Sci, I-20129 Milan, Italy
[4] Bristol Myers Squibb Co, Pharmaceut Res Inst, Seattle, WA 98121 USA
[5] Univ Washington, Hlth Sci Ctr, Reg Primate Res Ctr, Seattle, WA 98195 USA
关键词
HIV-2; vaccine; animal models; virology quantitative;
D O I
10.1006/viro.1997.8992
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
M. nemestrina immunized with an apathogenic HIV-2 molecular clone (HIV-2(KR)) were protected from CD4 decline and disease upon challenge with HIV-2(287), after any immunizing virus could be detected. Higher but not lower inocula of HIV-2(KR) were protective against intravenous inoculation of either 10(5) or 10(1) TCID(50) of HIV-2(287). Protected animals displayed substantial reductions in PBMC proviral burden (1-3 logs), viral titers (1-2 logs), and plasma viral RNA (2-4 logs) compared to unprotected or naive animals as early as 1 week postinfection. Plasma viral RNA became undetectable after 24 weeks in protected animals, but remained high in unprotected animals, No viral RNA was present in the spleen of the protected animal necropsied more than a year after challenge (though viral DNA was still present). No neutralizing responses could be demonstrated, but CTL activity was detected sooner and at higher levels after challenge in protected than in unprotected macaques. In this novel HIV-2 vaccine model, protection was clearly dose-dependent, and clearance of challenge virus RNA from the plasma did not require detectable ongoing replication of the immunizing virus at the time of challenge, (C) 1998 Academic Press.
引用
收藏
页码:150 / 160
页数:11
相关论文
共 42 条
  • [1] HIV-1 RECOMBINANT POXVIRUS VACCINE INDUCES CROSS-PROTECTION AGAINST HIV-2 CHALLENGE IN RHESUS MACAQUES
    ABIMIKU, AG
    FRANCHINI, G
    TARTAGLIA, J
    ALDRICH, K
    MYAGKIKH, M
    MARKHAM, PD
    CHONG, PL
    KLEIN, M
    KIENY, MP
    PAOLETTI, E
    GALLO, RC
    ROBERTGUROFF, M
    [J]. NATURE MEDICINE, 1995, 1 (04) : 321 - 329
  • [2] 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
  • [3] PATHOGENICITY OF LIVE, ATTENUATED SIV AFTER MUCOSAL INFECTION OF NEONATAL MACAQUES
    BABA, TW
    JEONG, YS
    PENNINCK, D
    BRONSON, R
    GREENE, MF
    RUPRECHT, RM
    [J]. SCIENCE, 1995, 267 (5205) : 1820 - 1825
  • [4] VIROLOGICAL AND IMMUNOLOGICAL CHARACTERIZATION OF LONG-TERM SURVIVORS OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INFECTION
    CAO, YZ
    QIN, LM
    ZHANG, LQ
    SAFRIT, J
    HO, DD
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 1995, 332 (04) : 201 - 208
  • [5] USE OF A NEW CD4-POSITIVE HELA-CELL CLONE FOR DIRECT QUANTITATION OF INFECTIOUS HUMAN-IMMUNODEFICIENCY-VIRUS FROM BLOOD-CELLS OF AIDS PATIENTS
    CHESEBRO, B
    WEHRLY, K
    METCALF, J
    GRIFFIN, DE
    [J]. JOURNAL OF INFECTIOUS DISEASES, 1991, 163 (01) : 64 - 70
  • [6] CROSS-PROTECTIVE IMMUNE-RESPONSES INDUCED IN RHESUS MACAQUES BY IMMUNIZATION WITH ATTENUATED MACROPHAGE-TROPIC SIMIAN IMMUNODEFICIENCY VIRUS
    CLEMENTS, JE
    MONTELARO, RC
    ZINK, MC
    AMEDEE, AM
    MILLER, S
    TRICHEL, AM
    JAGERSKI, B
    HAUER, D
    MARTIN, LN
    BOHM, RP
    MURPHEYCORB, M
    [J]. JOURNAL OF VIROLOGY, 1995, 69 (05) : 2737 - 2744
  • [7] 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
  • [8] EARLY SUPPRESSION OF SIV REPLICATION BY CD8+ NEF-SPECIFIC CYTOTOXIC T-CELLS IN VACCINATED MACAQUES
    GALLIMORE, A
    CRANAGE, M
    COOK, N
    ALMOND, N
    BOOTMAN, J
    RUD, E
    SILVERA, P
    DENNIS, M
    CORCORAN, T
    STOTT, J
    MCMICHAEL, A
    GOTCH, F
    [J]. NATURE MEDICINE, 1995, 1 (11) : 1167 - 1173
  • [9] MAJOR HISTOCOMPATIBILITY COMPLEX CLASS I-ASSOCIATED VACCINE PROTECTION FROM SIMIAN IMMUNODEFICIENCY VIRUS-INFECTED PERIPHERAL-BLOOD CELLS
    HEENEY, JL
    VANELS, C
    DEVRIES, P
    TENHAAFT, P
    OTTING, N
    KOORNSTRA, W
    BOES, J
    DUBBES, R
    NIPHUIS, H
    DINGS, M
    CRANAGE, M
    NORLEY, S
    JONKER, M
    BONTROP, RE
    OSTERHAUS, A
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1994, 180 (02) : 769 - 774
  • [10] Patterns of viral replication correlate with outcome in simian immunodeficiency virus (SIV)-infected macaques: Effect of prior immunization with a trivalent SIV vaccine in modified vaccinia virus Ankara
    Hirsch, VM
    Fuerst, TR
    Sutter, G
    Carroll, MW
    Yang, LC
    Goldstein, S
    Piatak, M
    Elkins, WR
    Alvord, WG
    Montefiori, DC
    Moss, B
    Lifson, JD
    [J]. JOURNAL OF VIROLOGY, 1996, 70 (06) : 3741 - 3752