A CONSERVED NEUTRALIZING EPITOPE ON GP41 OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1

被引:921
作者
MUSTER, T
STEINDL, F
PURTSCHER, M
TRKOLA, A
KLIMA, A
HIMMLER, G
RUKER, F
KATINGER, H
机构
关键词
D O I
10.1128/JVI.67.11.6642-6647.1993
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Vaccination against human immunodeficiency virus type 1 (HIV-1) requires an immunogen which will elicit a protective immunity against viruses that show a high degree of genetic polymorphism. Therefore, the identification of neutralizing epitopes which are shared by many strains would be useful. In previous studies, we established a human monoclonal antibody (2F5) that neutralizes a variety of laboratory strains and clinical isolates of HIV-1. In the present report, we define the amino acid sequence Glu-Leu-Asp-Lys-Trp-Ala (ELDKWA) on the ectodomain of gp41 as the epitope recognized by this antibody. The sequence was found to be conserved in 72% of otherwise highly variable HIV-1 isolates. Escape mutants were not detected in cells infected with HIV-1 isolates MN and RF in the presence of antibody 2F5. Since sequence variability of neutralizing epitopes is considered to be a major obstacle to HIV-1 vaccine development, the conserved B-cell epitope described here is a promising candidate for inclusion in a vaccine against AIDS.
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页码:6642 / 6647
页数:6
相关论文
共 38 条
[11]   RETROVIRAL RECOMBINATION DURING REVERSE TRANSCRIPTION [J].
GOODRICH, DW ;
DUESBERG, PH .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1990, 87 (06) :2052-2056
[12]   TUMOR PROMOTER, TPA, ENHANCES REPLICATION OF HTLV-III LAV [J].
HARADA, S ;
KOYANAGI, Y ;
NAKASHIMA, H ;
KOBAYASHI, N ;
YAMAMOTO, N .
VIROLOGY, 1986, 154 (02) :249-258
[13]   MECHANISMS ASSOCIATED WITH THE GENERATION OF BIOLOGICALLY-ACTIVE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 PARTICLES FROM DEFECTIVE PROVIRUSES [J].
INOUE, M ;
HOXIE, JA ;
REDDY, MVR ;
SRINIVASAN, A ;
REDDY, EP .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (06) :2278-2282
[14]   BROADLY NEUTRALIZING ANTIBODIES ELICITED BY THE HYPERVARIABLE NEUTRALIZING DETERMINANT OF HIV-1 [J].
JAVAHERIAN, K ;
LANGLOIS, AJ ;
LAROSA, GJ ;
PROFY, AT ;
BOLOGNESI, DP ;
HERLIHY, WC ;
PUTNEY, SD ;
MATTHEWS, TJ .
SCIENCE, 1990, 250 (4987) :1590-1593
[15]   ANTI-HIV AND ANTI-ANTI-MHC ANTIBODIES IN ALLOIMMUNE AND AUTOIMMUNE MICE [J].
KION, TA ;
HOFFMANN, GW .
SCIENCE, 1991, 253 (5024) :1138-1140
[16]   CONSERVED SEQUENCE AND STRUCTURAL ELEMENTS IN THE HIV-1 PRINCIPAL NEUTRALIZING DETERMINANT [J].
LAROSA, GJ ;
DAVIDE, JP ;
WEINHOLD, K ;
WATERBURY, JA ;
PROFY, AT ;
LEWIS, JA ;
LANGLOIS, AJ ;
DREESMAN, GR ;
BOSWELL, RN ;
SHADDUCK, P ;
HOLLEY, LH ;
KARPLUS, M ;
BOLOGNESI, DP ;
MATTHEWS, TJ ;
EMINI, EA ;
PUTNEY, SD .
SCIENCE, 1990, 249 (4971) :932-935
[17]   TYPE-RESTRICTED NEUTRALIZATION OF MOLECULAR CLONES OF HUMAN IMMUNODEFICIENCY VIRUS [J].
LOONEY, DJ ;
FISHER, AG ;
PUTNEY, SD ;
RUSCHE, JR ;
REDFIELD, RR ;
BURKE, DS ;
GALLO, RC ;
WONGSTAAL, F .
SCIENCE, 1988, 241 (4863) :357-359
[18]  
MASUDA T, 1990, J IMMUNOL, V145, P3240
[19]   CHARACTERIZATION OF HIV-1 NEUTRALIZATION ESCAPE MUTANTS [J].
MCKEATING, JA ;
GOW, J ;
GOUDSMIT, J ;
PEARL, LH ;
MULDER, C ;
WEISS, RA .
AIDS, 1989, 3 (12) :777-784
[20]  
Muster T. H., UNPUB