Recombinant respiratory syncytial virus (RSV) bearing a set of mutations from cold-passaged RSV is attenuated in chimpanzees

被引:74
作者
Whitehead, SS [1 ]
Juhasz, K [1 ]
Firestone, CY [1 ]
Collins, PL [1 ]
Murphy, BR [1 ]
机构
[1] NIAID, Infect Dis Lab, Resp Viruses Sect, Bethesda, MD 20892 USA
关键词
D O I
10.1128/JVI.72.5.4467-4471.1998
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
A set of five missense mutations previously identified by nucleotide sequence analysis of subgroup A cold-passaged (cp) respiratory syncytial virus (RSV) has been introduced into a recombinant wild-type strain of RSV. This recombinant virus, designated rA2cp, appears to replicate less efficiently in the upper and lower respiratory tracts of seronegative chimpanzees than either biologically derived or recombinant wild-type RSV. Infection with rA2cp also resulted in significantly less rhinorrhea and cough than infection with wild-type RSV. These findings confirm the role of the cp mutations in attenuation of RSV and identify their usefulness for inclusion in future live attenuated recombinant RSV vaccine candidates.
引用
收藏
页码:4467 / 4471
页数:5
相关论文
共 26 条
[1]   DETERMINANTS OF ATTENUATION AND TEMPERATURE SENSITIVITY IN THE TYPE-1 POLIOVIRUS SABIN VACCINE [J].
BOUCHARD, MJ ;
LAM, DH ;
RACANIELLO, VR .
JOURNAL OF VIROLOGY, 1995, 69 (08) :4972-4978
[2]   Recombinant respiratory syncytial virus from which the entire SH gene has been deleted grows efficiently in cell culture and exhibits site-specific attenuation in the respiratory tract of the mouse [J].
Bukreyev, A ;
Whitehead, SS ;
Murphy, BR ;
Collins, PL .
JOURNAL OF VIROLOGY, 1997, 71 (12) :8973-8982
[3]  
CHANOCK RM, 1991, ANIMAL MODELS RESP S, P35
[4]   PRODUCTION OF INFECTIOUS HUMAN RESPIRATORY SYNCYTIAL VIRUS FROM CLONED CDNA CONFIRMS AN ESSENTIAL ROLE FOR THE TRANSCRIPTION ELONGATION-FACTOR FROM THE 5'-PROXIMAL OPEN READING FRAME OF THE M2 MESSENGER-RNA IN GENE-EXPRESSION AND PROVIDES A CAPABILITY FOR VACCINE DEVELOPMENT [J].
COLLINS, PL ;
HILL, MG ;
CAMARGO, E ;
GROSFELD, H ;
CHANOCK, RM ;
MURPHY, BR .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (25) :11563-11567
[5]  
COLLINS PL, 1996, FIELDS VIROLOGY, V2, P1313
[6]   A COLD-PASSAGED, ATTENUATED STRAIN OF HUMAN RESPIRATORY SYNCYTIAL VIRUS CONTAINS MUTATIONS IN THE F-GENES AND L-GENES [J].
CONNORS, M ;
CROWE, JE ;
FIRESTONE, CY ;
MURPHY, BR ;
COLLINS, PL .
VIROLOGY, 1995, 208 (02) :478-484
[7]   SATISFACTORILY ATTENUATED AND PROTECTIVE MUTANTS DERIVED FROM A PARTIALLY ATTENUATED COLD-PASSAGED RESPIRATORY SYNCYTIAL VIRUS MUTANT BY INTRODUCTION OF ADDITIONAL ATTENUATING MUTATIONS DURING CHEMICAL MUTAGENESIS [J].
CROWE, JE ;
BUI, PT ;
LONDON, WT ;
DAVIS, AR ;
HUNG, PP ;
CHANOCK, RM ;
MURPHY, BR .
VACCINE, 1994, 12 (08) :691-699
[8]   COLD PASSAGED, TEMPERATURE-SENSITIVE MUTANTS OF HUMAN RESPIRATORY SYNCYTIAL VIRUS (RSV) ARE HIGHLY ATTENUATED, IMMUNOGENIC, AND PROTECTIVE IN SERONEGATIVE CHIMPANZEES, EVEN WHEN RSV ANTIBODIES ARE INFUSED SHORTLY BEFORE IMMUNIZATION [J].
CROWE, JE ;
BUI, PT ;
SIBER, GR ;
ELKINS, WR ;
CHANOCK, RM ;
MURPHY, BR .
VACCINE, 1995, 13 (09) :847-855
[9]   A FURTHER ATTENUATED DERIVATIVE OF A COLD-PASSAGED TEMPERATURE-SENSITIVE MUTANT OF HUMAN RESPIRATORY SYNCYTIAL VIRUS RETAINS IMMUNOGENICITY AND PROTECTIVE EFFICACY AGAINST WILD-TYPE CHALLENGE IN SERONEGATIVE CHIMPANZEES [J].
CROWE, JE ;
BUI, PT ;
DAVIS, AR ;
CHANOCK, RM ;
MURPHY, BR .
VACCINE, 1994, 12 (09) :783-790
[10]   Acquisition of the ts phenotype by a chemically mutagenized cold-passaged human respiratory syncytial virus vaccine candidate results from the acquisition of a single mutation in the polymerase (L) gene [J].
Crowe, JE ;
Firestone, CY ;
Whitehead, SS ;
Collins, PL ;
Murphy, BR .
VIRUS GENES, 1996, 13 (03) :269-273