TY - JOUR
T1 - Modifications of the human immunodeficiency virus envelope glycoprotein enhance immunogenicity for genetic immunization
AU - Chakrabarti, Bimal K.
AU - Kong, Wing Pui
AU - Wu, Bei Yue
AU - Yang, Zhi Yong
AU - Friborg, Jacques
AU - Ling, Xu
AU - King, Steven R.
AU - Montefiori, David C.
AU - Nabel, Gary J.
PY - 2002
Y1 - 2002
N2 - 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, gp140ΔCFI, stimulated the antibody response to native gp160 while it retained its ability to induce a CTL response, a desirable feature for an AIDS vaccine.
AB - 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, gp140ΔCFI, stimulated the antibody response to native gp160 while it retained its ability to induce a CTL response, a desirable feature for an AIDS vaccine.
UR - http://www.scopus.com/inward/record.url?scp=0036096976&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036096976&partnerID=8YFLogxK
U2 - 10.1128/JVI.76.11.5357-5368.2002
DO - 10.1128/JVI.76.11.5357-5368.2002
M3 - Article
C2 - 11991964
AN - SCOPUS:0036096976
SN - 0022-538X
VL - 76
SP - 5357
EP - 5368
JO - Journal of Virology
JF - Journal of Virology
IS - 11
ER -