Neutralizing antibodies have limited effects on the control of established HIV-1 infection in vivo

被引:193
作者
Poignard, P
Sabbe, R
Picchio, GR
Wang, M
Gulizia, RJ
Katinger, H
Parren, PWHI
Mosier, DE
Burtons, DR [1 ]
机构
[1] Scripps Res Inst, Dept Immunol, La Jolla, CA 92037 USA
[2] Scripps Res Inst, Dept Biol Mol, La Jolla, CA 92037 USA
[3] Agr Univ Vienna, Inst Appl Microbiol, A-1190 Vienna, Austria
关键词
D O I
10.1016/S1074-7613(00)80043-6
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Neutralizing antibodies can protect against challenge with HIV-1 in vivo if present at appropriate concentrations at the time of viral challenge, but any role in the control of established infection is unclear. Here, we show that high serum concentrations of neutralizing monoclonal antibodies, either singly or as a cocktail, have little sustained effect on viral load in established HIV-1 infection in hu-PBL-SCID mice. In some instances, virus replication of neutralization-sensitive virus continues even in the presence of high levels of neutralizing antibody. In most instances, neutralization escape occurs in a few days, even from a cocktail of three antibodies that recognize distinct epitopes. The results imply that humoral immunity is unlikely to play a significant role in the control of established HIV-1 infection in humans.
引用
收藏
页码:431 / 438
页数:8
相关论文
共 35 条
  • [1] RAPID DEVELOPMENT OF ISOLATE-SPECIFIC NEUTRALIZING ANTIBODIES AFTER PRIMARY HIV-1 INFECTION AND CONSEQUENT EMERGENCE OF VIRUS VARIANTS WHICH RESIST NEUTRALIZATION BY AUTOLOGOUS SERA
    ALBERT, J
    ABRAHAMSSON, B
    NAGY, K
    AURELIUS, E
    GAINES, H
    NYSTROM, G
    FENYO, EM
    [J]. AIDS, 1990, 4 (02) : 107 - 112
  • [2] Passive immunization with a human immunodeficiency virus type 1-neutralizing monoclonal antibody in Hu-PBL-SCID mice: Isolation of a neutralization escape variant
    Andrus, L
    Prince, AM
    Bernal, I
    McCormack, P
    Lee, DH
    Gorny, MK
    Zolla-Pazner, S
    [J]. JOURNAL OF INFECTIOUS DISEASES, 1998, 177 (04) : 889 - 897
  • [3] ARENDRUP M, 1992, J ACQ IMMUN DEF SYND, V5, P303
  • [4] EFFICIENT NEUTRALIZATION OF PRIMARY ISOLATES OF HIV-1 BY A RECOMBINANT HUMAN MONOCLONAL-ANTIBODY
    BURTON, DR
    PYATI, J
    KODURI, R
    SHARP, SJ
    THORNTON, GB
    PARREN, PWHI
    SAWYER, LSW
    HENDRY, RM
    DUNLOP, N
    NARA, PL
    LAMACCHIA, M
    GARRATTY, E
    STIEHM, ER
    BRYSON, YJ
    CAO, YZ
    MOORE, JP
    HO, DD
    BARBAS, CF
    [J]. SCIENCE, 1994, 266 (5187) : 1024 - 1027
  • [5] A LARGE ARRAY OF HUMAN MONOCLONAL-ANTIBODIES TO TYPE-1 HUMAN-IMMUNODEFICIENCY-VIRUS FROM COMBINATORIAL LIBRARIES OF ASYMPTOMATIC SEROPOSITIVE INDIVIDUALS
    BURTON, DR
    BARBAS, CF
    PERSSON, MAA
    KOENIG, S
    CHANOCK, RM
    LERNER, RA
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (22) : 10134 - 10137
  • [6] Burton DR, 1997, AIDS, V11, pS87
  • [7] DISTINCT BIOLOGICAL AND SEROLOGICAL PROPERTIES OF HUMAN IMMUNODEFICIENCY VIRUSES FROM THE BRAIN
    CHENGMAYER, C
    LEVY, JA
    [J]. ANNALS OF NEUROLOGY, 1988, 23 : S58 - S61
  • [8] HIV POPULATION-DYNAMICS IN-VIVO - IMPLICATIONS FOR GENETIC-VARIATION, PATHOGENESIS, AND THERAPY
    COFFIN, JM
    [J]. SCIENCE, 1995, 267 (5197) : 483 - 489
  • [9] Evaluation of monoclonal antibodies to human immunodeficiency virus type 1 primary isolates by neutralization assays: Performance criteria for selecting candidate antibodies for clinical trials
    DSouza, MP
    Livnat, D
    Bradac, JA
    Bridges, SH
    Bryson, Y
    Hanson, C
    Matthews, T
    Moore, J
    Trkola, A
    ZollaPazner, S
    Gorny, M
    Burton, D
    Merigan, T
    McNamara, J
    Norcross, M
    Posner, M
    Robinson, J
    ViraniKetter, N
    Barbas, CF
    Parren, P
    Katinger, H
    [J]. JOURNAL OF INFECTIOUS DISEASES, 1997, 175 (05) : 1056 - 1062
  • [10] PREEXPOSURE AND POSTEXPOSURE PROTECTION AGAINST HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INFECTION MEDIATED BY A MONOCLONAL-ANTIBODY
    GAUDUIN, MC
    SAFRIT, JT
    WEIR, R
    FUNG, MSC
    KOUP, RA
    [J]. JOURNAL OF INFECTIOUS DISEASES, 1995, 171 (05) : 1203 - 1209