Modifications of the human immunodeficiency virus envelope glycoprotein enhance immunogenicity for genetic immunization.
In this study, we have investigated the effect of specific mutations in human immunodeficiency virus type 1 (HIV-1) envelope (Env) on antibody production in an effort to improve humoral immune responses to this glycoprotein by DNA vaccination. Mice were injected with plasmid expression vectors encoding HIV Env with modifications in regions that might affect this response. Elimination of conserved glycosylation sites did not substantially enhance humoral or cytotoxic-T-lymphocyte (CTL) immunity. In contrast, a modified gp140 with different COOH-terminal mutations intended to mimic a fusion intermediate and stabilize trimer formation enhanced humoral immunity without reducing the efficacy of the CTL response. This mutant, with deletions in the cleavage site, fusogenic domain, and spacing of heptad repeats 1 and 2, retained native antigenic conformational determinants as defined by binding to known monoclonal antibodies or CD4, oligomer formation, and virus neutralization in vitro. Importantly, this modified Env, gp140 Delta CFI, stimulated the antibody response to native gp160 while it retained its ability to induce a CTL response, a desirable feature for an AIDS vaccine.
Chakrabarti
Bimal K
BK
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-3005, USA.
Kong
Wing-pui
WP
Wu
Bei-yue
BY
Yang
Zhi-Yong
ZY
Friborg
Jacques
J
Ling
Xu
X
King
Steven R
SR
Montefiori
David C
DC
Nabel
Gary J
GJ
D016915:AIDS Vaccines / Q000235:genetics / Q000276:immunology*; D000818:Animals; D002461:Cell Line, Transformed; D005260:Female; D015686:Gene Products, env / Q000235:genetics / Q000276:immunology*; D005822:Genetic Vectors; D006168:Guinea Pigs; D015483:HIV Antibodies / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000276:immunology; D019302:HIV Envelope Protein gp160 / Q000235:genetics / Q000276:immunology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D014611:Vaccination; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology*; D054299:env Gene Products, Human Immunodeficiency Virus
D016915:AIDS Vaccines; D015686:Gene Products, env; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D019302:HIV Envelope Protein gp160; D008562:Membrane Glycoproteins; D019444:Vaccines, DNA; D054299:env Gene Products, Human Immunodeficiency Virus; C097729:gp140 envelope protein, Human immunodeficiency virus 1