title: Codon optimization and ubiquitin conjugation of human immunodeficiency virus-1 Tat lead to enhanced cell-mediated immune responses.
abstract: The transactivator protein, Tat, is a potential candidate for developing a vaccine against human immunodeficiency virus (HIV-1). Since Tat is not immunodominant, especially when delivered as a genetic vaccine, we expressed codon-optimized subtype-C Tat as a molecular conjugate of ubiquitin, to elicit antigen-specific cell-mediated immune responses. Immunization of mice with different ubiquitin-Tat constructs elicited a strong cellular, but not a humoral, immune response. The combination of codon-optimization and ubiquitin-mediated processing of Tat induced a Th-1 type cellular immune response that was detectable without in vitro stimulation, suggesting its potential utility for destruction of virus-infected cells via CTL-mediated lysis. Preliminary attempts at characterizing the immunodominant regions identified a novel T-helper epitope within the core domain of Tat.
authors.affiliation: Molecular Virology Laboratory, Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur (PO), Bangalore 560064, India.
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Ramakrishna
authors.forename: Krishnamurthy Kumar
authors.initials: KK
authors.lastname: Anand
authors.forename: Marthandan
authors.initials: M
authors.lastname: Mahalingam
authors.forename: Kumarasamypet M
authors.initials: KM
authors.lastname: Mohankumar
authors.forename: Shilpa
authors.initials: S
authors.lastname: Ramani
authors.forename: Nagadenahalli B
authors.initials: NB
authors.lastname: Siddappa
authors.forename: Udaykumar
authors.initials: U
authors.lastname: Ranga
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology*; D000818:Animals; D003062:Codon; D000939:Epitopes / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D025801:Ubiquitin / Q000378:metabolism*; D018074:Vaccines, Conjugate / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D003062:Codon; D000939:Epitopes; D025801:Ubiquitin; D018074:Vaccines, Conjugate; C421254:human immunodeficiency virus type 1 Tat vaccine