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 journalArticle

11 Citations (Scopus)

Abstract

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
JournalVaccine
Volume26
Issue number25
DOIs
Publication statusPublished - Jun 13 2008

Fingerprint

SAIDS Vaccines
DNA Vaccines
recombinant vaccines
Cellular Immunity
cell-mediated immunity
monoclonal antibodies
Monoclonal Antibodies
Macaca
T-lymphocytes
Macaca fascicularis
Costimulatory and Inhibitory T-Cell Receptors
T-Lymphocytes
gag Gene Products
Antibodies, Monoclonal, Humanized
antigens
Antigens
DNA

Keywords

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

ASJC Scopus subject areas

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

Cite this

Calarota, S. A., Hokey, D. A., Dai, A., Jure-Kunkel, M. N., Balimane, P., & Weiner, D. B. (2008). Augmentation of SIV DNA vaccine-induced cellular immunity by targeting the 4-1BB costimulatory molecule. Vaccine, 26(25), 3121-3134. https://doi.org/10.1016/j.vaccine.2008.02.017

Augmentation of SIV DNA vaccine-induced cellular immunity by targeting the 4-1BB costimulatory molecule. / Calarota, Sandra A.; Hokey, David A.; Dai, Anlan; Jure-Kunkel, Maria N.; Balimane, Praveen; Weiner, David B.

In: Vaccine, Vol. 26, No. 25, 13.06.2008, p. 3121-3134.

Research output: Contribution to journalArticle

Calarota, SA, Hokey, DA, Dai, A, Jure-Kunkel, MN, Balimane, P & Weiner, DB 2008, 'Augmentation of SIV DNA vaccine-induced cellular immunity by targeting the 4-1BB costimulatory molecule', Vaccine, vol. 26, no. 25, pp. 3121-3134. https://doi.org/10.1016/j.vaccine.2008.02.017
Calarota, Sandra A. ; Hokey, David A. ; Dai, Anlan ; Jure-Kunkel, Maria N. ; Balimane, Praveen ; Weiner, David B. / Augmentation of SIV DNA vaccine-induced cellular immunity by targeting the 4-1BB costimulatory molecule. In: Vaccine. 2008 ; Vol. 26, No. 25. pp. 3121-3134.
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