Antigenic properties of recombinant envelope glycoproteins derived from T-cell-line-adapted isolates or primary human immunodeficiency virus isolates and their relationship to immunogenicity.
The native envelope glycoproteins of primary HIV-1 virions have weaker antigenicity than do T-cell laboratory-adapted (TCLA) viruses. These antigenic properties require further evaluation if recombinant envelope glycoproteins are produced as part of a vaccine strategy. In this study, we compared the antigenicity of recombinant envelope glycoproteins derived from three primary isolates (PI) (HIV-1(BX08), HIV-1(CHA), and HIV-1(133)) and two TCLA viruses (HIV-1(HXB2) and HIV-1(MN)) produced using the Semliki Forest virus (SFV) system. This analysis was performed by radioimmunoprecipitation assays and flow cytometry. The results suggest that the SFV produces envelope glycoproteins with features in common with the envelopes found in naturally occurring virions. In particular, the PI envelopes had weak heterogeneous antigenic properties. However, the cytometric analysis also showed that there was less envelope glycoprotein on the cell surface for the PI envelopes than for those of TCLA viruses, suggesting differences in their intracellular trafficking. The immunogenic properties of the various envelope glycoproteins were evaluated in mice using recombinant SFV particles as vaccine vectors. The PI envelopes were less immunogenic than the TCLA envelopes, probably due to both their low antigenicity and cell surface expression level. Thus, it may be difficult to design an effective vaccine based on native recombinant PI envelopes.
Brand
D
D
Unité de Virologie, Université François Rabelais, Tours, France. brand@med.univ-tours.fr
Lemiale
F
F
Thibault
G
G
Verrier
B
B
Lebigot
S
S
Roingeard
P
P
Buzelay
L
L
Brunet
S
S
Barin
F
F
D000222:Adaptation, Physiological; D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D005434:Flow Cytometry / Q000379:methods; D006023:Glycoproteins / Q000235:genetics / Q000276:immunology*; D015488:HIV Antigens / Q000235:genetics / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000276:immunology*; D019302:HIV Envelope Protein gp160 / Q000235:genetics / Q000276:immunology*; D015700:HIV Envelope Protein gp41 / Q000235:genetics / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology* / Q000302:isolation & purification / Q000502:physiology; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D011233:Precipitin Tests; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000821:virology
D006023:Glycoproteins; D015488:HIV Antigens; D015699:HIV Envelope Protein gp120; D019302:HIV Envelope Protein gp160; D015700:HIV Envelope Protein gp41; D011993:Recombinant Fusion Proteins