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.
AIDS Res Hum Retroviruses
; 11(10): 1187-95, 1995 Oct.
Article
in En
| MEDLINE
| ID: mdl-8573374
ABSTRACT
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.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Protein Precursors
/
HIV Antibodies
/
Gene Products, env
/
Protein Processing, Post-Translational
/
HIV-1
/
AIDS Vaccines
Limits:
Animals
/
Humans
Language:
En
Journal:
AIDS Res Hum Retroviruses
Journal subject:
SINDROME DA IMUNODEFICIENCIA ADQUIRIDA (AIDS)
Year:
1995
Type:
Article
Affiliation country:
Canada