title: Antigenicity and immunogenicity of HIV-1 consensus subtype B envelope glycoproteins.
abstract: "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.
authors.affiliation: Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: Denise L
authors.initials: DL
authors.lastname: Kothe
authors.forename: Julie M
authors.initials: JM
authors.lastname: Decker
authors.forename: Yingying
authors.initials: Y
authors.lastname: Li
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Weng
authors.forename: Frederic
authors.initials: F
authors.lastname: Bibollet-Ruche
authors.forename: Kenneth P
authors.initials: KP
authors.lastname: Zammit
authors.forename: Maria G
authors.initials: MG
authors.lastname: Salazar
authors.forename: Yalu
authors.initials: Y
authors.lastname: Chen
authors.forename: Jesus F
authors.initials: JF
authors.lastname: Salazar-Gonzalez
authors.forename: Zina
authors.initials: Z
authors.lastname: Moldoveanu
authors.forename: Jiri
authors.initials: J
authors.lastname: Mestecky
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.forename: Barton F
authors.initials: BF
authors.lastname: Haynes
authors.forename: George M
authors.initials: GM
authors.lastname: Shaw
authors.forename: Mark
authors.initials: M
authors.lastname: Muldoon
authors.forename: Bette T M
authors.initials: BT
authors.lastname: Korber
authors.forename: Beatrice H
authors.initials: BH
authors.lastname: Hahn
mesh_terms: 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*
chemical_list: 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