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A synthetic codon-optimized hepatitis C virus nonstructural 5A DNA vaccine primes polyfunctional CD8+ T cell responses in wild-type and NS5A-transgenic mice

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A synthetic codon-optimized hepatitis C virus nonstructural 5A DNA vaccine primes polyfunctional CD8+ T cell responses in wild-type and NS5A-transgenic mice. / Holmström, Fredrik; Pasetto, Anna; Nähr, Veronica; Brass, Anette; Kriegs, Malte; Hildt, Eberhard; Broderick, Kate E; Chen, Margaret; Ahlén, Gustaf; Frelin, Lars.

In: J IMMUNOL, Vol. 190, No. 3, 01.02.2013, p. 1113-24.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Holmström, F, Pasetto, A, Nähr, V, Brass, A, Kriegs, M, Hildt, E, Broderick, KE, Chen, M, Ahlén, G & Frelin, L 2013, 'A synthetic codon-optimized hepatitis C virus nonstructural 5A DNA vaccine primes polyfunctional CD8+ T cell responses in wild-type and NS5A-transgenic mice', J IMMUNOL, vol. 190, no. 3, pp. 1113-24. https://doi.org/10.4049/jimmunol.1201497

APA

Holmström, F., Pasetto, A., Nähr, V., Brass, A., Kriegs, M., Hildt, E., Broderick, K. E., Chen, M., Ahlén, G., & Frelin, L. (2013). A synthetic codon-optimized hepatitis C virus nonstructural 5A DNA vaccine primes polyfunctional CD8+ T cell responses in wild-type and NS5A-transgenic mice. J IMMUNOL, 190(3), 1113-24. https://doi.org/10.4049/jimmunol.1201497

Vancouver

Holmström F, Pasetto A, Nähr V, Brass A, Kriegs M, Hildt E et al. A synthetic codon-optimized hepatitis C virus nonstructural 5A DNA vaccine primes polyfunctional CD8+ T cell responses in wild-type and NS5A-transgenic mice. J IMMUNOL. 2013 Feb 1;190(3):1113-24. https://doi.org/10.4049/jimmunol.1201497

Bibtex

@article{e74d99aca22f40869971509f0a0fe06c,
title = "A synthetic codon-optimized hepatitis C virus nonstructural 5A DNA vaccine primes polyfunctional CD8+ T cell responses in wild-type and NS5A-transgenic mice",
abstract = "The hepatitis C virus (HCV) nonstructural (NS) 5A protein has been shown to promote viral persistence by interfering with both innate and adaptive immunity. At the same time, the HCV NS5A protein has been suggested as a target for antiviral therapy. In this study, we performed a detailed characterization of HCV NS5A immunogenicity in wild-type (wt) and immune tolerant HCV NS5A-transgenic (Tg) C57BL/6J mice. We evaluated how efficiently HCV NS5A-based genetic vaccines could activate strong T cell responses. Truncated and full-length wt and synthetic codon-optimized NS5A genotype 1b genes were cloned into eukaryotic expression plasmids, and the immunogenicity was determined after i.m. immunization in combination with in vivo electroporation. The NS5A-based genetic vaccines primed high Ab levels, with IgG titers of >10(4) postimmunization. With respect to CD8(+) T cell responses, the coNS5A gene primed more potent IFN-γ-producing and lytic cytotoxic T cells in wt mice compared with NS5A-Tg mice. In addition, high frequencies of NS5A-specific CD8(+) T cells were found in wt mice after a single immunization. To test the functionality of the CTL responses, the ability to inhibit growth of NS5A-expressing tumor cells in vivo was analyzed after immunization. A single dose of coNS5A primed tumor-inhibiting responses in both wt and NS5A-Tg mice. Finally, immunization with the coNS5A gene primed polyfunctional NS5A-specific CD8(+) T cell responses. Thus, the coNS5A gene is a promising therapeutic vaccine candidate for chronic HCV infections.",
keywords = "Animals, Antibody Specificity, Antigens, Neoplasm, CD8-Positive T-Lymphocytes, Cancer Vaccines, Codon, Cytotoxicity, Immunologic, DNA, Viral, Genes, Synthetic, H-2 Antigens, Hepacivirus, Hepatitis C Antibodies, Immunization, Immunoglobulin G, Lymphocyte Activation, Lymphokines, Lymphoma, Non-Hodgkin, Mice, Mice, Inbred C57BL, Mice, Transgenic, Peptide Fragments, T-Cell Antigen Receptor Specificity, T-Lymphocytes, Cytotoxic, Vaccines, DNA, Viral Hepatitis Vaccines, Viral Nonstructural Proteins",
author = "Fredrik Holmstr{\"o}m and Anna Pasetto and Veronica N{\"a}hr and Anette Brass and Malte Kriegs and Eberhard Hildt and Broderick, {Kate E} and Margaret Chen and Gustaf Ahl{\'e}n and Lars Frelin",
year = "2013",
month = feb,
day = "1",
doi = "10.4049/jimmunol.1201497",
language = "English",
volume = "190",
pages = "1113--24",
journal = "J IMMUNOL",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "3",

}

RIS

TY - JOUR

T1 - A synthetic codon-optimized hepatitis C virus nonstructural 5A DNA vaccine primes polyfunctional CD8+ T cell responses in wild-type and NS5A-transgenic mice

AU - Holmström, Fredrik

AU - Pasetto, Anna

AU - Nähr, Veronica

AU - Brass, Anette

AU - Kriegs, Malte

AU - Hildt, Eberhard

AU - Broderick, Kate E

AU - Chen, Margaret

AU - Ahlén, Gustaf

AU - Frelin, Lars

PY - 2013/2/1

Y1 - 2013/2/1

N2 - The hepatitis C virus (HCV) nonstructural (NS) 5A protein has been shown to promote viral persistence by interfering with both innate and adaptive immunity. At the same time, the HCV NS5A protein has been suggested as a target for antiviral therapy. In this study, we performed a detailed characterization of HCV NS5A immunogenicity in wild-type (wt) and immune tolerant HCV NS5A-transgenic (Tg) C57BL/6J mice. We evaluated how efficiently HCV NS5A-based genetic vaccines could activate strong T cell responses. Truncated and full-length wt and synthetic codon-optimized NS5A genotype 1b genes were cloned into eukaryotic expression plasmids, and the immunogenicity was determined after i.m. immunization in combination with in vivo electroporation. The NS5A-based genetic vaccines primed high Ab levels, with IgG titers of >10(4) postimmunization. With respect to CD8(+) T cell responses, the coNS5A gene primed more potent IFN-γ-producing and lytic cytotoxic T cells in wt mice compared with NS5A-Tg mice. In addition, high frequencies of NS5A-specific CD8(+) T cells were found in wt mice after a single immunization. To test the functionality of the CTL responses, the ability to inhibit growth of NS5A-expressing tumor cells in vivo was analyzed after immunization. A single dose of coNS5A primed tumor-inhibiting responses in both wt and NS5A-Tg mice. Finally, immunization with the coNS5A gene primed polyfunctional NS5A-specific CD8(+) T cell responses. Thus, the coNS5A gene is a promising therapeutic vaccine candidate for chronic HCV infections.

AB - The hepatitis C virus (HCV) nonstructural (NS) 5A protein has been shown to promote viral persistence by interfering with both innate and adaptive immunity. At the same time, the HCV NS5A protein has been suggested as a target for antiviral therapy. In this study, we performed a detailed characterization of HCV NS5A immunogenicity in wild-type (wt) and immune tolerant HCV NS5A-transgenic (Tg) C57BL/6J mice. We evaluated how efficiently HCV NS5A-based genetic vaccines could activate strong T cell responses. Truncated and full-length wt and synthetic codon-optimized NS5A genotype 1b genes were cloned into eukaryotic expression plasmids, and the immunogenicity was determined after i.m. immunization in combination with in vivo electroporation. The NS5A-based genetic vaccines primed high Ab levels, with IgG titers of >10(4) postimmunization. With respect to CD8(+) T cell responses, the coNS5A gene primed more potent IFN-γ-producing and lytic cytotoxic T cells in wt mice compared with NS5A-Tg mice. In addition, high frequencies of NS5A-specific CD8(+) T cells were found in wt mice after a single immunization. To test the functionality of the CTL responses, the ability to inhibit growth of NS5A-expressing tumor cells in vivo was analyzed after immunization. A single dose of coNS5A primed tumor-inhibiting responses in both wt and NS5A-Tg mice. Finally, immunization with the coNS5A gene primed polyfunctional NS5A-specific CD8(+) T cell responses. Thus, the coNS5A gene is a promising therapeutic vaccine candidate for chronic HCV infections.

KW - Animals

KW - Antibody Specificity

KW - Antigens, Neoplasm

KW - CD8-Positive T-Lymphocytes

KW - Cancer Vaccines

KW - Codon

KW - Cytotoxicity, Immunologic

KW - DNA, Viral

KW - Genes, Synthetic

KW - H-2 Antigens

KW - Hepacivirus

KW - Hepatitis C Antibodies

KW - Immunization

KW - Immunoglobulin G

KW - Lymphocyte Activation

KW - Lymphokines

KW - Lymphoma, Non-Hodgkin

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Transgenic

KW - Peptide Fragments

KW - T-Cell Antigen Receptor Specificity

KW - T-Lymphocytes, Cytotoxic

KW - Vaccines, DNA

KW - Viral Hepatitis Vaccines

KW - Viral Nonstructural Proteins

U2 - 10.4049/jimmunol.1201497

DO - 10.4049/jimmunol.1201497

M3 - SCORING: Journal article

C2 - 23284053

VL - 190

SP - 1113

EP - 1124

JO - J IMMUNOL

JF - J IMMUNOL

SN - 0022-1767

IS - 3

ER -