Enhanced T- and B-cell responses to simian immunodeficiency virus (SIV)agm, SIVmac and human immunodeficiency virus type 1 Gag DNA immunization and identification of novel T-cell epitopes in mice via codon optimization.
As a prelude to primate studies, the immunogenicity of wild-type and codon-optimized versions of simian immunodeficiency virus (SIV)agm Gag DNA, with and without co-administered granulocyte-macrophage colony-stimulating factor (GM-CSF) DNA, was directly compared in two strains of mice. Gag-specific T cells in the splenocytes of BALB/c and C57BL/6 mice immunized by gene gun were quantified by ELISpot using panels of overlapping synthetic peptides (15mers) spanning the entire capsid proteins of SIVagm, SIVmac and human immunodeficiency virus type 1. Specific antibodies were measured by ELISA. Codon optimization was shown to significantly increase the immune response to the DNA immunogens, reducing the amount of DNA necessary to induce cellular and antibody responses by one and two orders of magnitude, respectively. Co-administration of murine GM-CSF DNA was necessary for the induction of high level T- and B-cell responses. Finally, it was possible to identify both known and novel T-cell epitopes in the Gag proteins of the three viruses.
Siegismund
Christine S
CS
Robert Koch-Institute, Nordufer 20, 13353 Berlin, Germany.
Hohn
Oliver
O
Robert Koch-Institute, Nordufer 20, 13353 Berlin, Germany.
Kurth
Reinhard
R
Robert Koch-Institute, Nordufer 20, 13353 Berlin, Germany.
Norley
Stephen
S
Robert Koch-Institute, Nordufer 20, 13353 Berlin, Germany.
D000595:Amino Acid Sequence; D000818:Animals; D004279:DNA, Viral / Q000276:immunology*; D015686:Gene Products, env / Q000737:chemistry / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D015682:Retroviridae Proteins, Oncogenic / Q000737:chemistry / Q000276:immunology*; D015302:Simian Immunodeficiency Virus; D013154:Spleen / Q000166:cytology; D019444:Vaccines, DNA / Q000276:immunology*; D014760:Viral Fusion Proteins / Q000737:chemistry / Q000276:immunology*; D014779:Virus Replication; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000737:chemistry / Q000276:immunology*
D004279:DNA, Viral; D015686:Gene Products, env; D015682:Retroviridae Proteins, Oncogenic; D019444:Vaccines, DNA; D014760:Viral Fusion Proteins; D054301:gag Gene Products, Human Immunodeficiency Virus; C059580:transmembrane protein, Simian immunodeficiency virus