Hepatitis C virus NS3/NS4A DNA vaccine induces multiepitope T cell responses in rhesus macaques mimicking human immune responses

Krystle A. Lang Kuhs, Arielle A. Ginsberg, Jian Yan, Roger W. Wiseman, Amir S. Khan, Niranjan Y. Sardesai, David H. O'Connor, David B. Weiner

Research output: Contribution to journalArticlepeer-review

31 Scopus citations


Numerous studies have suggested that an effective hepatitis C virus (HCV) vaccine must induce a strong T helper 1 (Th1) T cell response. While several therapeutic vaccine candidates have shown promise in clinical trials, response rates have been low suggesting that further optimization is important. However, such optimization has been hindered by a lack of a benchmark animal model in which to test vaccine-induced immune responses before clinical evaluation. The goal of this study was to analyze the utility of the rhesus macaque vaccination model in assessing HCV vaccine-induced T cell responses. To test this, we employed the use of a novel HCV genotype 1a/1b consensus DNA vaccine encoding both HCV nonstructural protein 3 (NS3) and nonstructural protein 4A (NS4A) proteins. Following immunization, rhesus macaques mounted HCV-specific responses strikingly similar to those reported in resolving patients, including strong NS3-specific interferon-γ (IFN-γ) responses, robust CD4+ and CD8 T cell proliferation, and induction of polyfunctional T cells. Additionally, fine epitope mapping revealed one animal that mounted a T cell response against a known HCV NS3 human leukocyte antigen A2 (HLA-A2) epitope previously identified in humans. Taken together our findings suggest that the rhesus macaque vaccination model is a useful tool in the evaluation of immune responses induced by HCV immunogens.

Original languageEnglish
Pages (from-to)669-678
Number of pages10
JournalMolecular Therapy
Issue number3
StatePublished - Mar 2012

Bibliographical note

Funding Information:
This work was supported by the Cancer Research Institute training grant “Predoctoral Emphasis Pathway in Tumor Immunology” (KLK). This manuscript was supported in part by funding from the NIH to DBW and from Inovio Pharmaceuticals. Grant Support: Cure Grant—PA Department of Health—7 August 2007. The authors note possible commercial conflicts associated with this work, which may include Wyeth, Inovio, BMS, Virxsys, Ichor, Merck, Althea, and Aldeveron.

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery


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