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

Lang Kuhs KA, Ginsberg AA, Yan J, Wiseman RW, Khan AS, Sardesai NY, O'Connor DH, Weiner DB
Mol Ther. 2012 20 (3): 669-78

PMID: 21952169 · PMCID: PMC3293616 · DOI:10.1038/mt.2011.188

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.

MeSH Terms (16)

Animals CD4-Positive T-Lymphocytes CD8-Positive T-Lymphocytes Cytokines Epitope Mapping Epitopes, T-Lymphocyte Genes, MHC Class I Genotype Hepacivirus Humans Lymphocyte Activation Macaca mulatta T-Lymphocytes Vaccines, DNA Viral Hepatitis Vaccines Viral Nonstructural Proteins

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