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M9630041.TXT
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1996-02-27
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Document 0041
DOCN M9630041
TI Immune responses induced by administration of encapsidated poliovirus
replicons which express HIV-1 gag and envelope proteins.
DT 9603
AU Moldoveanu Z; Porter DC; Lu A; McPherson S; Morrow CD; Department of
Microbiology, University of Alabama at Birmingham; 35294, USA.
SO Vaccine. 1995 Aug;13(11):1013-22. Unique Identifier : AIDSLINE
MED/96088054
AB Several viruses have been exploited for the development of recombinant
vaccine vectors in which to express foreign proteins. Recently, we have
described a system utilizing the RNA virus, poliovirus. We have
constructed poliovirus genomes in which regions of the capsid have been
substituted with gene fragments of the HIV gag and env genes. A
complementation system has been designed to encapsidate defective
genomes by providing the capsid protein in trans from a recombinant
vaccinia virus (VV-P1). Serial passage in the presence of VV-P1 resulted
in the generation of stocks of these encapsidated replicons. Infection
of cells with these encapsidated replicons resulted in the expression of
the recombinant protein as a fusion protein with the poliovirus capsid
proteins VP4 and VP1. In this study, we have utilized encapsidated
replicons which express the HIV-1-gag capsid protein (p24) as well as
1.5 kb of the HIV-1 env gene. Stocks of these encapsidated replicons
were obtained by 20 serial passages in the presence of VV-P1. In
addition, passage of the encapsidated replicons in the presence of
poliovirus type 2 Lansing resulted in the encapsidation of the replicons
by the capsid proteins provided by poliovirus. The administration of the
type 2 Lansing/encapsidated replicons expressing HIV-1 gag in BALB/c
mice by intramuscular, intrarectal, or intragastric routes resulted in
the generation of antibodies in the serum and secretions against both
poliovirus and HIV-1 gag. To prove that the replicons alone are
immunogenic, we administered replicons expressing either HIV-1 gag or
env to transgenic mice which expressed the receptor for poliovirus type
1. Immunization of these mice by the intramuscular route resulted in the
generation of serum antibodies specific for poliovirus as well as for
HIV-1 antigens. The results obtained led us to the conclusion that the
replicons are immunogenic when given alone or in the presence of
poliovirus. These results are important for the use of the poliovirus
replicons as a recombinant vaccine vector.
DE Animal Antibodies, Viral/*BIOSYNTHESIS AIDS Vaccines/ADMINISTRATION &
DOSAGE/*IMMUNOLOGY Capsid/GENETICS/*IMMUNOLOGY Gene Products,
env/GENETICS Hela Cells Human HIV Antibodies/*BIOSYNTHESIS HIV Core
Protein p24/*IMMUNOLOGY Mice Mice, Inbred BALB C Mice, Transgenic
Polioviruses, Human 1-3/GENETICS/*IMMUNOLOGY Recombinant Fusion
Proteins/BIOSYNTHESIS Replicon/*IMMUNOLOGY Serial Passage Support,
U.S. Gov't, P.H.S. Vaccines, Synthetic/ADMINISTRATION &
DOSAGE/IMMUNOLOGY Viral Envelope Proteins/GENETICS/*IMMUNOLOGY JOURNAL
ARTICLE
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).