Antigenicity and immunogenicity of HIV-1 consensus subtype B envelope glycoproteins.
"Centralized" (ancestral and consensus) HIV-1 envelope immunogens induce broadly cross-reactive T cell responses in laboratory animals; however, their potential to elicit cross-reactive neutralizing antibodies has not been fully explored. Here, we report the construction of a panel of consensus subtype B (ConB) envelopes and compare their biologic, antigenic, and immunogenic properties to those of two wild-type Env controls from individuals with early and acute HIV-1 infection. Glycoprotein expressed from full-length (gp160), uncleaved (gp160-UNC), truncated (gp145), and N-linked glycosylation site deleted (gp160-201N/S) versions of the ConB env gene were packaged into virions and, except for the fusion defective gp160-UNC, mediated infection via the CCR5 co-receptor. Pseudovirions containing ConB Envs were sensitive to neutralization by patient plasma and monoclonal antibodies, indicating the preservation of neutralizing epitopes found in contemporary subtype B viruses. When used as DNA vaccines in guinea pigs, ConB and wild-type env immunogens induced appreciable binding, but overall only low level neutralizing antibodies. However, all four ConB immunogens were significantly more potent than one wild-type vaccine at eliciting neutralizing antibodies against a panel of tier 1 and tier 2 viruses, and ConB gp145 and gp160 were significantly more potent than both wild-type vaccines at inducing neutralizing antibodies against tier 1 viruses. Thus, consensus subtype B env immunogens appear to be at least as good as, and in some instances better than, wild-type B env immunogens at inducing a neutralizing antibody response, and are amenable to further improvement by specific gene modifications.
Kothe
Denise L
DL
Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Decker
Julie M
JM
Li
Yingying
Y
Weng
Zhiping
Z
Bibollet-Ruche
Frederic
F
Zammit
Kenneth P
KP
Salazar
Maria G
MG
Chen
Yalu
Y
Salazar-Gonzalez
Jesus F
JF
Moldoveanu
Zina
Z
Mestecky
Jiri
J
Gao
Feng
F
Haynes
Barton F
BF
Shaw
George M
GM
Muldoon
Mark
M
Korber
Bette T M
BT
Hahn
Beatrice H
BH
D016915:AIDS Vaccines / Q000008:administration & dosage; D000595:Amino Acid Sequence; D000818:Animals; D000918:Antibody Specificity; D005260:Female; D015752:Genes, env / Q000235:genetics; D014644:Genetic Variation; D006023:Glycoproteins / Q000235:genetics / Q000276:immunology; D006168:Guinea Pigs; D015483:HIV Antibodies / Q000097:blood / Q000276:immunology; D015488:HIV Antigens / Q000276:immunology; D019302:HIV Envelope Protein gp160 / Q000276:immunology; D015658:HIV Infections / Q000097:blood / Q000276:immunology*; D015497:HIV-1 / Q000145:classification / Q000276:immunology*; D006801:Humans; D007106:Immune Sera / Q000276:immunology; D007114:Immunization; D007273:Injections, Intramuscular; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D016415:Sequence Alignment; D013045:Species Specificity; D019444:Vaccines, DNA / Q000008:administration & dosage; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology*
D016915:AIDS Vaccines; D006023:Glycoproteins; D015483:HIV Antibodies; D015488:HIV Antigens; D019302:HIV Envelope Protein gp160; D007106:Immune Sera; D019444:Vaccines, DNA; D014759:Viral Envelope Proteins