Improving vaccine potency through intercellular spreading and enhanced MHC class I presentation of antigen.
The potency of naked DNA vaccines is limited by their inability to amplify and spread in vivo. VP22, a HSV-1 protein, has demonstrated the remarkable property of intercellular transport and may thus provide a unique approach for enhancing vaccine potency. Therefore, we created a novel fusion of VP22 with a model Ag, human papillomavirus type 16 E7, in a DNA vaccine that generated enhanced spreading and MHC class I presentation of AG: These properties led to a dramatic increase in the number of E7-specific CD8(+) T cell precursors in vaccinated mice (around 50-fold) and converted a less effective DNA vaccine into one with significant potency against E7-expressing tumors. In comparison, nonspreading VP22(1-267) mutants failed to enhance vaccine potency. Our data indicated that the potency of DNA vaccines may be dramatically improved through intercellular spreading and enhanced MHC class I presentation of Ag.
Hung
C F
CF
Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD 21205, USA.
Cheng
W F
WF
Chai
C Y
CY
Hsu
K F
KF
He
L
L
Ling
M
M
Wu
T C
TC
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D017951:Antigen Presentation / Q000235:genetics; D019470:Biolistics; D001692:Biological Transport / Q000235:genetics / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005110:Extracellular Space / Q000235:genetics / Q000276:immunology*; D005822:Genetic Vectors / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D007271:Injections, Intradermal; D008175:Lung Neoplasms / Q000276:immunology / Q000517:prevention & control / Q000628:therapy; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D009856:Oncogene Proteins, Viral / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D027383:Papillomaviridae / Q000235:genetics / Q000276:immunology; D050725:Papillomavirus E7 Proteins; D013234:Stem Cells / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology* / Q000378:metabolism*; D015678:Viral Structural Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
D000276:Adjuvants, Immunologic; D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D019444:Vaccines, DNA; D015678:Viral Structural Proteins; C073413:herpes simplex virus type 1 protein VP22; C059731:oncogene protein E7, Human papillomavirus type 16