Development of a synthetic consensus sequence scrambled antigen HIV-1 vaccine designed for global use.
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.
Thomson
Scott A
SA
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
Jaramillo
Angel B
AB
Shoobridge
Maryanne
M
Dunstan
Kerrie J
KJ
Everett
Beth
B
Ranasinghe
Charani
C
Kent
Stephen J
SJ
Gao
Ke
K
Medveckzy
Jill
J
Ffrench
Rosemary A
RA
Ramshaw
Ian A
IA
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
D016915:AIDS Vaccines; D000939:Epitopes; D015488:HIV Antigens; D014614:Vaccines, Synthetic