کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2406986 | 1103105 | 2008 | 14 صفحه PDF | دانلود رایگان |

SummaryDNA vaccines are effective at inducing antigen-specific cellular immune responses. Approaches to improve these responses, however, are needed. We examined the effect of stimulating 4-1BB, an activation-inducible T-cell costimulatory receptor, by intravenously co-administering anti-human 4-1BB monoclonal antibody (mAb) in DNA-immunized cynomolgus macaques. Three groups of six cynomolgus macaques were immunized intramuscularly with a DNA vaccine encoding SIV Gag antigen (pSIVgag) at weeks 0, 4 and 8. At days 12, 15, and 19, six macaques received anti-4-1BB 4E9 mAb and six macaques received anti-4-1BB 10C7 mAb. Treatment with 10C7 mAb led to a significant augmentation of SIV Gag-specific IFN-γ, granzyme B and perforin responses. Treatment with humanized 4E9 mAb also resulted in an enhancement of SIV Gag-specific cellular responses but the magnitude was lower compared to animals receiving 10C7 mAb. These responses persisted up to week 40 and were mostly mediated by CD8+ T cells. Treatment with anti-4-1BB mAb was more effective in driving the CD8+ T cells toward a more differentiated CCR7−/CD45RA+ effector state. This study demonstrates that targeting the 4-1BB molecule in vivo results in an enhanced and long-lasting cellular immune response. 4-1BB stimulation may be a promising approach to enhance the effectiveness of DNA vaccines.
Journal: Vaccine - Volume 26, Issue 25, 13 June 2008, Pages 3121–3134