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.
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.
Rovinski
B
B
Department of Molecular Genetics, Connaught Centre for Biotechnology Research, Willowdale, Ontario, Canada.
Rodrigues
L
L
Cao
S X
SX
Yao
F L
FL
McGuinness
U
U
Sia
C
C
Cates
G
G
Zolla-Pazner
S
S
Karwowska
S
S
Matthews
T J
TJ
D016915:AIDS Vaccines / Q000235:genetics / Q000276:immunology*; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002499:Centrifugation, Density Gradient; D002522:Chlorocebus aethiops; D005240:Feasibility Studies; D015686:Gene Products, env / Q000276:immunology* / Q000378:metabolism; D006168:Guinea Pigs; D015483:HIV Antibodies / Q000096:biosynthesis* / Q000276:immunology; D019302:HIV Envelope Protein gp160; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007114:Immunization; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D011498:Protein Precursors / Q000276:immunology* / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology; D014709:Vero Cells
D016915:AIDS Vaccines; D015686:Gene Products, env; D015483:HIV Antibodies; D019302:HIV Envelope Protein gp160; D011498:Protein Precursors; D014614:Vaccines, Synthetic