Augmentation of SIV DNA vaccine-induced cellular immunity by targeting the 4-1BB costimulatory molecule

Sandra A. Calarota, David A. Hokey, Anlan Dai, Maria N. Jure-Kunkel, Praveen Balimane, David B. Weiner

Research output: Contribution to journalArticlepeer-review


DNA 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.

Original languageEnglish
Pages (from-to)3121-3134
Number of pages14
Issue number25
Publication statusPublished - Jun 13 2008


  • 4-1BB
  • DNA
  • HIV
  • SIV
  • Vaccine

ASJC Scopus subject areas

  • Immunology
  • Microbiology
  • Virology
  • Infectious Diseases
  • Public Health, Environmental and Occupational Health
  • veterinary(all)


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