       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).

