Memory T cells and vaccines

Esser, Mark T.; Marchese, Rocio D.; Kierstead, Lisa; Tussey, Lynda; Wang, Fubao; Chirmule, Narendra; Washabaugh, Michael W.

doi:10.1016/s0264-410x(02)00407-3

Cited by 167 publications

(143 citation statements)

References 106 publications

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“…An effective vaccine against HCV infection should be capable of inducing strong, cross-reactive, helper T-cell (Th) and cytotoxic T-lymphocyte (CTL) responses (Esser et al, 2003;Neumann-Haefelin et al, 2005). A major inherent problem in the design of an effective vaccine against HCV infection is the heterogeneity of its genome (Pawlotsky, 2003;Simmonds, 1999).…”

Section: Introductionmentioning

confidence: 99%

Dendritic cells pulsed with hepatitis C virus NS3 protein induce immune responses and protection from infection with recombinant vaccinia virus expressing NS3

Huang

Xiang

et al. 2006

Journal of General Virology

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Infections with Hepatitis C virus (HCV) pose a serious health problem worldwide. In this study, the hypothesis that adoptive transfer of dendritic cells (DCs) pulsed with HCV NS3 protein and matured with an oligodeoxynucleotide (ODN) containing CpG motifs (CpG) ex vivo would initiate potent HCV-specific protective immune responses in vivo was tested. NS3 protein was efficiently transduced into DCs and treatment of DCs with CpG ODN induced phenotypic maturation and specifically increased the expression of CD40. DCs matured with CpG ODN produced higher interleukin 12 levels and a stronger allogeneic T-cell response compared with untreated DCs. Notably, there were no differences between NS3-pulsed DCs and DCs pulsed with a control protein with respect to phenotype, cytokine production or mixed lymphocyte reaction, indicating that transduction with NS3 protein did not impair DC functions. Compared with the untreated NS3-pulsed DCs, the NS3-pulsed DCs matured with CpG ODN induced stronger cellular immune responses including enhanced cytotoxicity, higher interferon-c production and stronger lymphocyte proliferation. Upon challenge with a recombinant vaccinia virus expressing NS3, all mice immunized with NS3-pulsed DCs showed a significant reduction in vaccinia virus titres when compared with mock-immunized mice. However, the NS3-pulsed DCs matured with CpG ODN induced higher levels of protection compared with the untreated NS3-pulsed DCs. These data are the first to show that NS3-pulsed DCs induce specific immune responses and provide protection from viral challenge, and also demonstrate that CpG ODNs, which have a proven safety profile, would be useful in the development of DC vaccines. INTRODUCTIONInfections with Hepatitis C virus (HCV) pose a serious health problem worldwide. An estimated 170 million people are currently infected, which amounts to 3 % of the world population. About 80 % of infected people remain chronic carriers and are at high risk of developing severe liver disease including cirrhosis and hepatocellular carcinoma (WHO, 1999). Treatment with interferon-a (IFN-a) and ribavirin is the only effective therapy against HCV infection, but the overall response rate is only 40-50 % (Fried et al., 2002;Manns et al., 2001). Currently, there is no licensed vaccine against HCV; therefore, developing strategies for vaccination as well as for treatment of HCV infection is of great importance.Dendritic cells (DCs) are the most potent type of antigen presenting cells (APCs) and are responsible for the initiation and maintenance of immune responses. Situated in peripheral tissues and in lymphoid organs, DCs are uniquely suited to detect and capture pathogens. They express members of the recently identified Toll-like receptor (TLR) family, which bind common chemical moieties associated with microbial organisms. TLR ligands include bacterial lipopolysaccharide, lipopeptides, hypomethylated CpG DNA motifs, dsRNA and flagellin (Akira et al., 2001;Iwasaki & Medzhitov, 2004). TLR signalling triggers a maturation program...

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Section: Introductionmentioning

confidence: 99%

Dendritic cells pulsed with hepatitis C virus NS3 protein induce immune responses and protection from infection with recombinant vaccinia virus expressing NS3

Huang

Xiang

et al. 2006

Journal of General Virology

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“…The role of CD8 ϩ CTL in the protection from heterologous influenza virus infection is well established by the use of CD8 ϩ CTL clones, CTL lines, or T-cell receptor (TCR) transgenic mice and believed to be dependent on the cytotoxic potential of the cell (13,18,19). It appears that CTL prevent the disease by first slowing the spread of the infection and then eliminating the pathogen reservoir (11,13). Plasticity in the recognition of influenza virus-specific CTL (induced by natural infection) is not restricted to cross-strain protection but extends to other viral infections (29).…”

mentioning

confidence: 99%

Protective Efficacy of a DNA Influenza Virus Vaccine Is Markedly Increased by the Coadministration of a Schiff Base-Forming Drug

Charo¹,

Lindencrona²,

Carlson³

et al. 2004

J Virol

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Effective vaccination against heterologous influenza virus infection remains elusive. Immunization with plasmid DNA (pDNA) expressing conserved genes from influenza virus is a promising approach to achieve cross-variant protection. However, despite having been described for more than a decade, pDNA vaccination still requires further optimization to be applied clinically as a standard vaccination approach. We have recently described a simple and efficient approach to enhance pDNA immunization, based on the use of tucaresol, a Schiff base-forming drug. In this report we have tested the ability of this drug to increase the protection conferred by pDNA vaccination against influenza virus infection. Our results demonstrate that a significant protection was achieved in two strains of mice by using the combination of pDNA and tucaresol. This protection was associated with an elevated humoral and cellular response and a switch in the type of the T helper cell (Th) immune response from type 2 to type 1. This vaccine combination represents a promising strategy for designing a clinical study for the protection from influenza and similar infections.

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“…Lymphocytes, such as CD4 ϩ T cells, are known to secrete cytokines in response to viral infection and memory T cells that recognize epitopes on the infecting virus are rapidly activated to produce cytokines (6,16). Because rotavirus shedding is quickly suppressed after EDIM challenge of VP6/LT(R192G)-immunized mice and CD4 ϩ T cells were found to be critical to VP6/LT(R192G)-induced protection, it is possible that one or more of these cytokines is directly or indirectly responsible for this protection.…”

Section: Discussionmentioning

confidence: 99%

Association of Gamma Interferon and Interleukin-17 Production in Intestinal CD4⁺T Cells with Protection against Rotavirus Shedding in Mice Intranasally Immunized with VP6 and the Adjuvant LT(R192G)

Smiley

McNeal

Basu

et al. 2007

J Virol

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Mucosal immunization of mice with chimeric, Escherichia coli-expressed VP6, the protein that comprises the intermediate capsid layer of the rotavirus particle, together with attenuated E. coli heat-labile toxin LT(R192G) as an adjuvant, reduces fecal shedding of rotavirus antigen by >95% after murine rotavirus challenge, and the only lymphocytes required for protection are CD4 ؉ T cells. Because these cells produce cytokines with antiviral properties, the cytokines whose expression is upregulated in intestinal memory CD4؉ T cells immediately after rotavirus challenge of VP6/LT(R192G)-immunized mice may be directly or indirectly responsible for the rapid suppression of rotavirus shedding. This study was designed to identify which cytokines are significantly upregulated in intestinal effector sites and secondary lymphoid tissues of intranasally immunized BALB/c mice after challenge with murine rotavirus strain EDIM. Initially, this was done by using microarray analysis to quantify mRNAs for 96 murine common cytokines. With this procedure, the synthesis of mRNAs for gamma interferon (IFN-␥) and interleukin-17 (IL-17) was found to be temporarily upregulated in intestinal lymphoid cells of VP6/LT(R192G)-immunized mice at 12 h after rotavirus challenge. These cytokines were also produced in CD4؉ T cells obtained from intestinal sites specific to VP6/LT(R192G)-immunized mice after in vitro exposure to VP6 as determined by intracellular cytokine staining and secretion of cytokines. Although genetically modified mice that lack receptors for either IFN-␥ or IL-17 remained protected after immunization, these results provide suggestive evidence that these cytokines may play direct or indirect roles in protection against rotavirus after mucosal immunization of mice with VP6/LT(R192G).

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Memory T cells and vaccines

Cited by 167 publications

References 106 publications

Dendritic cells pulsed with hepatitis C virus NS3 protein induce immune responses and protection from infection with recombinant vaccinia virus expressing NS3

Dendritic cells pulsed with hepatitis C virus NS3 protein induce immune responses and protection from infection with recombinant vaccinia virus expressing NS3

Protective Efficacy of a DNA Influenza Virus Vaccine Is Markedly Increased by the Coadministration of a Schiff Base-Forming Drug

Association of Gamma Interferon and Interleukin-17 Production in Intestinal CD4⁺T Cells with Protection against Rotavirus Shedding in Mice Intranasally Immunized with VP6 and the Adjuvant LT(R192G)

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Memory T cells and vaccines

Cited by 167 publications

References 106 publications

Dendritic cells pulsed with hepatitis C virus NS3 protein induce immune responses and protection from infection with recombinant vaccinia virus expressing NS3

Dendritic cells pulsed with hepatitis C virus NS3 protein induce immune responses and protection from infection with recombinant vaccinia virus expressing NS3

Protective Efficacy of a DNA Influenza Virus Vaccine Is Markedly Increased by the Coadministration of a Schiff Base-Forming Drug

Association of Gamma Interferon and Interleukin-17 Production in Intestinal CD4+T Cells with Protection against Rotavirus Shedding in Mice Intranasally Immunized with VP6 and the Adjuvant LT(R192G)

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Association of Gamma Interferon and Interleukin-17 Production in Intestinal CD4⁺T Cells with Protection against Rotavirus Shedding in Mice Intranasally Immunized with VP6 and the Adjuvant LT(R192G)