title: Development of a synthetic consensus sequence scrambled antigen HIV-1 vaccine designed for global use.
abstract: Induction of high levels of broadly reactive cytotoxic T lymphocytes (CTL) remains a promising approach for an effective HIV-1 vaccine. We have developed a novel genetic-based vaccine strategy that encodes consensus overlapping peptide sets from all HIV-1 proteins scrambled together. This synthetic scrambled antigen vaccine (SAVINE) strategy has significant advantages, e.g. capacity to encode more antigens safely and is very flexible compared to traditional isolate-based strategies. The SAVINE vaccine strategy is clearly immunogenic, being able to restimulate a range of human HIV-1 specific responses in vitro and induce HIV-1 specific immunity in vivo in mice. Interestingly, different in vivo delivery strategies affected the resulting immunity and immunodominance pattern in mice. This platform strategy could be used for other infections and cancers where T cell responses are important for protection.
authors.affiliation: Division of Immunology and Genetics, John Curtin School of Medical Research (JCSMR), Australian National University, P.O. Box 334, Canberra, ACT 2601, Australia. Scott.Thomson@anu.edu.au
authors.forename: Scott A
authors.initials: SA
authors.lastname: Thomson
authors.forename: Angel B
authors.initials: AB
authors.lastname: Jaramillo
authors.forename: Maryanne
authors.initials: M
authors.lastname: Shoobridge
authors.forename: Kerrie J
authors.initials: KJ
authors.lastname: Dunstan
authors.forename: Beth
authors.initials: B
authors.lastname: Everett
authors.forename: Charani
authors.initials: C
authors.lastname: Ranasinghe
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Kent
authors.forename: Ke
authors.initials: K
authors.lastname: Gao
authors.forename: Jill
authors.initials: J
authors.lastname: Medveckzy
authors.forename: Rosemary A
authors.initials: RA
authors.lastname: Ffrench
authors.forename: Ian A
authors.initials: IA
authors.lastname: Ramshaw
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000276:immunology; D020816:Amino Acid Motifs / Q000276:immunology; D000818:Animals; D016384:Consensus Sequence / Q000276:immunology*; D000939:Epitopes; D015488:HIV Antigens / Q000008:administration & dosage* / Q000737:chemistry; D015658:HIV Infections / Q000517:prevention & control* / Q000628:therapy; D006801:Humans; D007114:Immunization / Q000379:methods; D051379:Mice; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000821:virology; D014614:Vaccines, Synthetic / Q000008:administration & dosage* / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D000939:Epitopes; D015488:HIV Antigens; D014614:Vaccines, Synthetic