DNA Vaccination Protects Mice Against Challenge with Listeria Monocytogenes Expressing the Hepatitis C Virus NS3 Protein

Overview

Journal Infect Immun

Publisher American Society for Microbiology

Specialty Allergy & Immunology

Date 2003 Oct 24

PMID 14573658

Citations 3

Authors

Benjamin E Simon

Kenneth A Cornell

Tina R Clark

Sunwen Chou

Hugo R Rosen

Ronald A Barry

Affiliations

Soon will be listed here.

Abstract

The goal of this study was to develop a new surrogate challenge model for use in evaluating protective cell-mediated immune responses against hepatitis C virus (HCV) antigens. The use of recombinant Listeria monocytogenes organisms which express HCV antigens provides novel tools with which to assay such in vivo protection, as expression of immunity against this hepatotropic bacterial pathogen is dependent on antigen-specific CD8(+) T lymphocytes. A plasmid DNA vaccine encoding a ubiquitin-NS3 fusion protein was generated, and its efficacy was confirmed by in vivo induction of NS3-specific, gamma interferon-secreting T cells following vaccination of BALB/c mice. These immunized mice also exhibited specific in vivo protection against subsequent challenge with a recombinant L. monocytogenes strain (TC-LNS3) expressing the NS3 protein. Notably, sublethal infection of naive mice with strain TC-LNS3 induced similar NS3-specific T-cell responses. These findings suggest that recombinant strains of L. monocytogenes expressing HCV antigens should prove useful for evaluating, or even inducing, protective immune responses against HCV antigens.

Citing Articles

Enhanced virus-specific CD8+ T cell responses by Listeria monocytogenes-infected dendritic cells in the context of Tim-3 blockade.

Ma C, Ren J, Li G, Wu X, Brockstedt D, Lauer P PLoS One. 2014; 9(1):e87821.

PMID: 24498204 PMC: 3909257. DOI: 10.1371/journal.pone.0087821.

A heterologous prime/boost vaccination strategy enhances the immunogenicity of therapeutic vaccines for hepatitis C virus.

Fournillier A, Frelin L, Jacquier E, Ahlen G, Brass A, Gerossier E J Infect Dis. 2013; 208(6):1008-19.

PMID: 23776192 PMC: 3749006. DOI: 10.1093/infdis/jit267.

Induction of broad CD4+ and CD8+ T-cell responses and cross-neutralizing antibodies against hepatitis C virus by vaccination with Th1-adjuvanted polypeptides followed by defective alphaviral particles expressing envelope glycoproteins gpE1 and gpE2....

Lin Y, Kwon T, Polo J, Zhu Y, Coates S, Crawford K J Virol. 2008; 82(15):7492-503.

PMID: 18508900 PMC: 2493334. DOI: 10.1128/JVI.02743-07.

References

Gordon E, Bhat R, Liu Q, Wang Y, Tackney C, Prince A . Immune responses to hepatitis C virus structural and nonstructural proteins induced by plasmid DNA immunizations. J Infect Dis. 1999; 181(1):42-50. DOI: 10.1086/315162. View

Scognamiglio P, Accapezzato D, Casciaro M, Cacciani A, Artini M, Bruno G . Presence of effector CD8+ T cells in hepatitis C virus-exposed healthy seronegative donors. J Immunol. 1999; 162(11):6681-9. View

Knolle P, Gerken G . Local control of the immune response in the liver. Immunol Rev. 2000; 174:21-34. DOI: 10.1034/j.1600-0528.2002.017408.x. View

Gregory S, Liu C . CD8+ T-cell-mediated response to Listeria monocytogenes taken up in the liver and replicating within hepatocytes. Immunol Rev. 2000; 174:112-22. DOI: 10.1034/j.1600-0528.2002.017405.x. View

Delogu G, Howard A, Collins F, Morris S . DNA vaccination against tuberculosis: expression of a ubiquitin-conjugated tuberculosis protein enhances antimycobacterial immunity. Infect Immun. 2000; 68(6):3097-102. PMC: 97537. DOI: 10.1128/IAI.68.6.3097-3102.2000. View

Cucchiarini M, Kammer A, Grabscheid B, Diepolder H, Gerlach T, Gruner N . Vigorous peripheral blood cytotoxic T cell response during the acute phase of hepatitis C virus infection. Cell Immunol. 2000; 203(2):111-23. DOI: 10.1006/cimm.2000.1683. View

Friedman R, Frankel F, Xu Z, Lieberman J . Induction of human immunodeficiency virus (HIV)-specific CD8 T-cell responses by Listeria monocytogenes and a hyperattenuated Listeria strain engineered to express HIV antigens. J Virol. 2000; 74(21):9987-93. PMC: 102037. DOI: 10.1128/jvi.74.21.9987-9993.2000. View

Bouwer H, Barry R, Hinrichs D . Lack of expansion of major histocompatibility complex class Ib-restricted effector cells following recovery from secondary infection with the intracellular pathogen Listeria monocytogenes. Infect Immun. 2001; 69(4):2286-92. PMC: 98157. DOI: 10.1128/IAI.69.4.2286-2292.2001. View

Lazdina U, Hultgren C, Frelin L, Chen M, Lodin K, Weiland O . Humoral and CD4(+) T helper (Th) cell responses to the hepatitis C virus non-structural 3 (NS3) protein: NS3 primes Th1-like responses more effectively as a DNA-based immunogen than as a recombinant protein. J Gen Virol. 2001; 82(Pt 6):1299-1308. DOI: 10.1099/0022-1317-82-6-1299. View

10.

Mercer D, Schiller D, Elliott J, Douglas D, Hao C, Rinfret A . Hepatitis C virus replication in mice with chimeric human livers. Nat Med. 2001; 7(8):927-33. DOI: 10.1038/90968. View

11.

Bukh J, Forns X, Emerson S, Purcell R . Studies of hepatitis C virus in chimpanzees and their importance for vaccine development. Intervirology. 2001; 44(2-3):132-42. DOI: 10.1159/000050040. View

12.

Wedemeyer H, Gagneten S, Davis A, Bartenschlager R, Feinstone S, Rehermann B . Oral immunization with HCV-NS3-transformed Salmonella: induction of HCV-specific CTL in a transgenic mouse model. Gastroenterology. 2001; 121(5):1158-66. DOI: 10.1053/gast.2001.29311. View

13.

Thimme R, Oldach D, Chang K, Steiger C, Ray S, Chisari F . Determinants of viral clearance and persistence during acute hepatitis C virus infection. J Exp Med. 2001; 194(10):1395-406. PMC: 2193681. DOI: 10.1084/jem.194.10.1395. View

14.

Brinster C, Muguet S, Lone Y, Boucreux D, Renard N, Fournillier A . Different hepatitis C virus nonstructural protein 3 (Ns3)-DNA-expressing vaccines induce in HLA-A2.1 transgenic mice stable cytotoxic T lymphocytes that target one major epitope. Hepatology. 2001; 34(6):1206-17. DOI: 10.1053/jhep.2001.29304. View

15.

Rosen H, Miner C, Sasaki A, Lewinsohn D, Conrad A, Bakke A . Frequencies of HCV-specific effector CD4+ T cells by flow cytometry: correlation with clinical disease stages. Hepatology. 2002; 35(1):190-8. DOI: 10.1053/jhep.2002.30293. View

16.

Ilan E, Arazi J, Nussbaum O, Zauberman A, Eren R, Lubin I . The hepatitis C virus (HCV)-Trimera mouse: a model for evaluation of agents against HCV. J Infect Dis. 2002; 185(2):153-61. DOI: 10.1086/338266. View

17.

Arribillaga L, Diaz de Cerio A, Sarobe P, Casares N, Gorraiz M, Vales A . Vaccination with an adenoviral vector encoding hepatitis C virus (HCV) NS3 protein protects against infection with HCV-recombinant vaccinia virus. Vaccine. 2002; 21(3-4):202-10. DOI: 10.1016/s0264-410x(02)00456-5. View

18.

Barry R, Archie Bouwer H, Clark T, Cornell K, Hinrichs D . Protection of interferon-gamma knockout mice against Listeria monocytogenes challenge following intramuscular immunization with DNA vaccines encoding listeriolysin O. Vaccine. 2003; 21(17-18):2122-32. DOI: 10.1016/s0264-410x(02)00780-6. View

19.

Mielke M, Ehlers S, Hahn H . T-cell subsets in delayed-type hypersensitivity, protection, and granuloma formation in primary and secondary Listeria infection in mice: superior role of Lyt-2+ cells in acquired immunity. Infect Immun. 1988; 56(8):1920-5. PMC: 259502. DOI: 10.1128/iai.56.8.1920-1925.1988. View

20.

Rosen H, Gordon S, NORTH R . Exacerbation of murine listeriosis by a monoclonal antibody specific for the type 3 complement receptor of myelomonocytic cells. Absence of monocytes at infective foci allows Listeria to multiply in nonphagocytic cells. J Exp Med. 1989; 170(1):27-37. PMC: 2189368. DOI: 10.1084/jem.170.1.27. View