Isolation of a second recombinant human respiratory syncytial virus monoclonal antibody fragment (Fab RSVF2-5) that exhibits therapeutic efficacy in vivo

被引:24
作者
Crowe, JE
Gilmour, PS
Murphy, BR
Chanock, RM
Duan, LX
Pomerantz, RJ
Pilkington, GR
机构
[1] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA
[2] Thomas Jefferson Univ, Jefferson Med Coll, Dept Med,Div Infect Dis, Ctr Human Virol,Dorrance Hamilton Labs, Philadelphia, PA 19107 USA
[3] Intracel Corp, Issaquah, WA USA
关键词
D O I
10.1086/517397
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
A second human respiratory syncytial virus (RSV)-neutralizing monoclonal antibody was isolated and its binding site was identified. Fab F2-5 is a broadly reactive fusion (F) protein-specific recombinant Fab generated by antigen selection from a random combinatorial library displayed on the surface of filamentous phage. In an in vitro plaque-reduction test, the Fab RSVF2-5 neutralized the infectivity of a variety of field isolates representing viruses of both RSV subgroups A and B. The Fab recognized an antigenic determinant that differed from the only other human anti-F monoclonal antibody (RSV Fab 19) described thus far. A single dose of 4.0 mg of Fab RSVF2-5/kg of body weight administered by inhalation was sufficient to achieve a 2000-fold reduction in pulmonary virus titer in RSV-infected mice. The antigen-binding domain of Fab RSVF2-5 offers promise as part of a prophylactic regimen for RSV infection in humans.
引用
收藏
页码:1073 / 1076
页数:4
相关论文
共 12 条
[1]   CHARACTERIZATION OF 2 ANTIGENIC SITES RECOGNIZED BY NEUTRALIZING MONOCLONAL-ANTIBODIES DIRECTED AGAINST THE FUSION GLYCOPROTEIN OF HUMAN RESPIRATORY SYNCYTIAL VIRUS [J].
ARBIZA, J ;
TAYLOR, G ;
LOPEZ, JA ;
FURZE, J ;
WYLD, S ;
WHYTE, P ;
STOTT, EJ ;
WERTZ, G ;
SULLENDER, W ;
TRUDEL, M ;
MELERO, JA .
JOURNAL OF GENERAL VIROLOGY, 1992, 73 :2225-2234
[2]   HUMAN MONOCLONAL FAB FRAGMENTS DERIVED FROM A COMBINATORIAL LIBRARY BIND TO RESPIRATORY SYNCYTIAL VIRUS-F GLYCOPROTEIN AND NEUTRALIZE INFECTIVITY [J].
BARBAS, CF ;
CROWE, JE ;
CABABA, D ;
JONES, TM ;
ZEBEDEE, SL ;
MURPHY, BR ;
CHANOCK, RM ;
BURTON, DR .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (21) :10164-10168
[3]   NEUTRALIZATION EPITOPES OF THE F-GLYCOPROTEIN OF RESPIRATORY SYNCYTIAL VIRUS - EFFECT OF MUTATION UPON FUSION FUNCTION [J].
BEELER, JA ;
COELINGH, KV .
JOURNAL OF VIROLOGY, 1989, 63 (07) :2941-2950
[4]   AN ANTIGENIC ANALYSIS OF RESPIRATORY SYNCYTIAL VIRUS ISOLATES BY A PLAQUE REDUCTION NEUTRALIZATION TEST [J].
COATES, HV ;
ALLING, DW ;
CHANOCK, RM .
AMERICAN JOURNAL OF EPIDEMIOLOGY, 1966, 83 (02) :299-&
[5]  
Collins P.L., 1996, FIELDS VIROLOGY, V3, P1313
[6]   RECOMBINANT HUMAN RESPIRATORY SYNCYTIAL VIRUS (RSV) MONOCLONAL-ANTIBODY FAB IS EFFECTIVE THERAPEUTICALLY WHEN INTRODUCED DIRECTLY INTO THE LUNGS OF RSV-INFECTED MICE [J].
CROWE, JE ;
MURPHY, BR ;
CHANOCK, RM ;
WILLIAMSON, RA ;
BARBAS, CF ;
BURTON, DR .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (04) :1386-1390
[7]   A COMPARISON IN CHIMPANZEES OF THE IMMUNOGENICITY AND EFFICACY OF LIVE ATTENUATED RESPIRATORY SYNCYTIAL VIRUS (RSV) TEMPERATURE-SENSITIVE MUTANT VACCINES AND VACCINIA VIRUS RECOMBINANTS THAT EXPRESS THE SURFACE GLYCOPROTEINS OF RSV [J].
CROWE, JE ;
COLLINS, PL ;
LONDON, WT ;
CHANOCK, RM ;
MURPHY, BR .
VACCINE, 1993, 11 (14) :1395-1404
[8]   ENHANCED PULMONARY HISTOPATHOLOGY IS OBSERVED IN COTTON RATS IMMUNIZED WITH FORMALIN-INACTIVATED RESPIRATORY SYNCYTIAL VIRUS (RSV) OR PURIFIED F-GLYCOPROTEIN AND CHALLENGED WITH RSV 3-6 MONTHS AFTER IMMUNIZATION [J].
MURPHY, BR ;
SOTNIKOV, AV ;
LAWRENCE, LA ;
BANKS, SM ;
PRINCE, GA .
VACCINE, 1990, 8 (05) :497-502
[9]   Recombinant human fab antibody fragments to HIV-1 REV and tat regulatory proteins: Direct selection from a combinatorial phage display library [J].
Pilkington, GR ;
Duan, LX ;
Zhu, MH ;
Keil, W ;
Pomerantz, RJ .
MOLECULAR IMMUNOLOGY, 1996, 33 (4-5) :439-450
[10]  
PRINCE GA, 1978, AM J PATHOL, V93, P771