Document 0734
 DOCN  M9650734
 TI    Induction of HIV type 1 neutralizing and env-CD4 blocking antibodies by
       immunization with genetically engineered HIV type 1-like particles
       containing unprocessed gp160 glycoproteins.
 DT    9605
 AU    Rovinski B; Rodrigues L; Cao SX; Yao FL; McGuinness U; Sia C; Cates G;
       Zolla-Pazner S; Karwowska S; Matthews TJ; et al; Department of Molecular
       Genetics, Connaught Centre for; Biotechnology Research, Willowdale,
       Ontario, Canada.
 SO    AIDS Res Hum Retroviruses. 1995 Oct;11(10):1187-95. Unique Identifier :
       AIDSLINE MED/96157206
 AB    Genetically engineered, noninfectious HIV-1-like particles containing
       processed envelope glycoproteins represent potential candidate
       immunogens for a vaccine against HIV-1. However, since the gp120
       glycoprotein is known to be rapidly lost from the surface of infected
       cells and purified virions as a result of its low-affinity interaction
       with gp41, shedding of this extracellular subunit could compromise the
       immunogenic potential of particle-based HIV-1 vaccine candidates. In
       this study, we demonstrate for the first time the feasibility of
       producing fully assembled HIV-1-like particles containing only
       unprocessed gp160 glycoproteins. Monkey kidney Vero cells were
       transfected with an inducible, human metallothionein-based expression
       vector containing most of the HIV-1LAI coding sequences that were
       genetically modified to introduce safety mutations and destroy the major
       cleavage site of the HIV-1 envelope glycoprotein. A stably-transfected
       cell line was isolated and shown to secrete HIV-1-like particles
       containing unprocessed gp160. Immunization with these particles induced
       HIV-1 cross-neutralizing, syncytium-inhibiting and env-CD4 blocking
       antibodies. Thus, these novel HIV-1-like particles represent alternative
       candidate immunogens for the development of a particle-based AIDS
       vaccine.
 DE    Animal  AIDS Vaccines/GENETICS/*IMMUNOLOGY  Base Sequence  Cell Line
       Centrifugation, Density Gradient  Cercopithecus aethiops  Feasibility
       Studies  Gene Products, env/*IMMUNOLOGY/METABOLISM  Guinea Pigs  Human
       HIV Antibodies/*BIOSYNTHESIS/IMMUNOLOGY  HIV-1/GENETICS/*IMMUNOLOGY
       Immunization  Molecular Sequence Data  Neutralization Tests  Protein
       Precursors/*IMMUNOLOGY/METABOLISM  *Protein Processing,
       Post-Translational  Support, Non-U.S. Gov't  Support, U.S. Gov't,
       Non-P.H.S.  Support, U.S. Gov't, P.H.S.  Vaccines,
       Synthetic/GENETICS/IMMUNOLOGY  Vero Cells  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).