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IL-12 DNA as molecular vaccine adjuvant increases the cytotoxic T cell responses and breadth of humoral immune responses in SIV DNA vaccinated macaques.

Publication ,  Journal Article
Jalah, R; Patel, V; Kulkarni, V; Rosati, M; Alicea, C; Ganneru, B; von Gegerfelt, A; Huang, W; Guan, Y; Broderick, KE; Sardesai, NY ...
Published in: Hum Vaccin Immunother
November 1, 2012

Intramuscular injection of macaques with an IL-12 expression plasmid (0.1 or 0.4 mg DNA/animal) optimized for high level of expression and delivered using in vivo electroporation, resulted in the detection of systemic IL-12 cytokine in the plasma. Peak levels obtained by day 4-5 post injection were paralleled by a rapid increase of IFN-γ, indicating bioactivity of the IL-12 cytokine. Both plasma IL-12 and IFN-γ levels were reduced to basal levels by day 14, indicating a short presence of elevated levels of the bioactive IL-12. The effect of IL-12 as adjuvant together with an SIVmac239 DNA vaccine was further examined comparing two groups of rhesus macaques vaccinated in the presence or absence of IL-12 DNA. The IL-12 DNA-adjuvanted group developed significantly higher SIV-specific cellular immune responses, including IFN-γ (+) Granzyme B (+) T cells, demonstrating increased levels of vaccine-induced T cells with cytotoxic potential, and this difference persisted for 6 mo after the last vaccination. Coinjection of IL-12 DNA led to increases in Gag-specific CD4 (+) and CD4 (+) CD8 (+) double-positive memory T cell subsets, whereas the Env-specific increases were mainly mediated by the CD8 (+) and CD4 (+) CD8 (+) double-positive memory T cell subsets. The IL-12 DNA-adjuvanted vaccine group developed higher binding antibody titers to Gag and mac251 Env, and showed higher and more durable neutralizing antibodies to heterologous SIVsmE660. Therefore, co-delivery of IL-12 DNA with the SIV DNA vaccine enhanced the magnitude and breadth of immune responses in immunized rhesus macaques, and supports the inclusion of IL-12 DNA as vaccine adjuvant.

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Published In

Hum Vaccin Immunother

DOI

EISSN

2164-554X

Publication Date

November 1, 2012

Volume

8

Issue

11

Start / End Page

1620 / 1629

Location

United States

Related Subject Headings

  • Vaccines, DNA
  • T-Lymphocytes, Cytotoxic
  • Simian immunodeficiency virus
  • Simian Immunodeficiency Virus
  • SAIDS Vaccines
  • Macaca mulatta
  • Macaca
  • Interleukin-12
  • Immunity, Humoral
  • Electroporation
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Jalah, R., Patel, V., Kulkarni, V., Rosati, M., Alicea, C., Ganneru, B., … Felber, B. K. (2012). IL-12 DNA as molecular vaccine adjuvant increases the cytotoxic T cell responses and breadth of humoral immune responses in SIV DNA vaccinated macaques. Hum Vaccin Immunother, 8(11), 1620–1629. https://doi.org/10.4161/hv.21407
Jalah, Rashmi, Vainav Patel, Viraj Kulkarni, Margherita Rosati, Candido Alicea, Brunda Ganneru, Agneta von Gegerfelt, et al. “IL-12 DNA as molecular vaccine adjuvant increases the cytotoxic T cell responses and breadth of humoral immune responses in SIV DNA vaccinated macaques.Hum Vaccin Immunother 8, no. 11 (November 1, 2012): 1620–29. https://doi.org/10.4161/hv.21407.
Jalah R, Patel V, Kulkarni V, Rosati M, Alicea C, Ganneru B, et al. IL-12 DNA as molecular vaccine adjuvant increases the cytotoxic T cell responses and breadth of humoral immune responses in SIV DNA vaccinated macaques. Hum Vaccin Immunother. 2012 Nov 1;8(11):1620–9.
Jalah, Rashmi, et al. “IL-12 DNA as molecular vaccine adjuvant increases the cytotoxic T cell responses and breadth of humoral immune responses in SIV DNA vaccinated macaques.Hum Vaccin Immunother, vol. 8, no. 11, Nov. 2012, pp. 1620–29. Pubmed, doi:10.4161/hv.21407.
Jalah R, Patel V, Kulkarni V, Rosati M, Alicea C, Ganneru B, von Gegerfelt A, Huang W, Guan Y, Broderick KE, Sardesai NY, LaBranche C, Montefiori DC, Pavlakis GN, Felber BK. IL-12 DNA as molecular vaccine adjuvant increases the cytotoxic T cell responses and breadth of humoral immune responses in SIV DNA vaccinated macaques. Hum Vaccin Immunother. 2012 Nov 1;8(11):1620–1629.

Published In

Hum Vaccin Immunother

DOI

EISSN

2164-554X

Publication Date

November 1, 2012

Volume

8

Issue

11

Start / End Page

1620 / 1629

Location

United States

Related Subject Headings

  • Vaccines, DNA
  • T-Lymphocytes, Cytotoxic
  • Simian immunodeficiency virus
  • Simian Immunodeficiency Virus
  • SAIDS Vaccines
  • Macaca mulatta
  • Macaca
  • Interleukin-12
  • Immunity, Humoral
  • Electroporation