In vivo antigen stability affects DNA vaccine immunogenicity.
The factors that determine the immunogenicity of Ags encoded by viral vaccines or DNA vaccines in vivo are largely unknown. Depending on whether T cell induction occurs via direct presentation of vaccine-encoded epitopes or via one of the different proposed pathways for Ag cross-presentation, the effect of intracellular Ag stability on immunogenicity may possibly vary. However, the influence of Ag stability on CD8(+) T cell induction has not been addressed in clinically relevant vaccine models, nor has the accumulation of vaccine-encoded Ags been monitored in vivo. In this study, we describe the relationship between in vivo Ag stability and immunogenicity of DNA vaccine-encoded Ags. We show that in vivo accumulation of DNA vaccine-encoded Ags is required for the efficient induction of CD8(+) T cell responses. These data suggest that many of the currently used transgene designs in DNA vaccination trials may be suboptimal, and that one should either use pathogen-derived or tumor-associated Ags that are intrinsically stable, or should increase the stability of vaccine-encoded Ags by genetic engineering.
Division of Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Adriaan D
AD
Bins
Monika C
MC
Wolkers
Marly D
MD
van den Boom
John B A G
JB
Haanen
Ton N M
TN
Schumacher
D000818:Animals; D017951:Antigen Presentation / Q000235:genetics / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005818:Genetic Engineering; D051379:Mice; D018345:Mice, Knockout; D018448:Models, Immunological; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology*; D014765:Viral Vaccines / Q000235:genetics / Q000276:immunology*
D000951:Antigens, Neoplasm; D000956:Antigens, Viral; D019444:Vaccines, DNA; D014765:Viral Vaccines