title: Enhanced cellular immune responses elicited by an engineered HIV-1 subtype B consensus-based envelope DNA vaccine.
abstract: An important goal for human immunodeficiency virus (HIV) vaccines is to develop immunogens that induce broader and more potent cellular immune responses. In this study of DNA vaccine potency, we constructed a novel subtype B env gene (EY2E1-B) with the goal of increasing vaccine antigen immune potency. The vaccine cassette was designed based on subtype B-specific consensus sequence with several modifications, including codon optimization, RNA optimization, the addition of a Kozak sequence, and a substituted immunoglobulin E leader sequence. The V1 and V2 loops were shortened and the cytoplasmic tail was truncated to prevent envelope recycling. Three different strains of mice (BALB/c, C57BL/6, and HLA-A2 transgenic mice) were immunized three times with pEY2E1-B or the primary DNA immunogen pEK2P-B alone. The analysis of specific antibody responses suggested that EY2E1-B could induce a moderate subtype B-specific antibody response. Moreover, this construct was up to four times more potent at driving cellular immune responses. Epitope mapping results indicated that there is an increase in the breadth and magnitude of cross-reactive cellular responses induced by the EY2E1-B immunogen. These properties suggest that such a synthetic immunogen deserves further examination for its potential to serve as a component antigen in an HIV vaccine cocktail.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Yan
authors.forename: Hanna
authors.initials: H
authors.lastname: Yoon
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Kumar
authors.forename: Mathura P
authors.initials: MP
authors.lastname: Ramanathan
authors.forename: Natasha
authors.initials: N
authors.lastname: Corbitt
authors.forename: Michele
authors.initials: M
authors.lastname: Kutzler
authors.forename: Anlan
authors.initials: A
authors.lastname: Dai
authors.forename: Jean D
authors.initials: JD
authors.lastname: Boyer
authors.forename: David B
authors.initials: DB
authors.lastname: Weiner
mesh_terms: D016915:AIDS Vaccines / Q000235:genetics / Q000276:immunology*; D000595:Amino Acid Sequence; D000818:Animals; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D015752:Genes, env / Q000235:genetics / Q000276:immunology*; D015488:HIV Antigens / Q000235:genetics / Q000276:immunology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D015789:HLA-A2 Antigen / Q000235:genetics / Q000276:immunology; D007111:Immunity, Cellular / Q000276:immunology*; D007114:Immunization / Q000379:methods; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D016415:Sequence Alignment
chemical_list: D016915:AIDS Vaccines; D015488:HIV Antigens; D015789:HLA-A2 Antigen