Induction of potent and long-lasting CD4 and CD8 T-cell responses against hepatitis C virus by immunization with viral antigens plus poly(I:C) and anti-CD40

Zabaleta, Aintzane; Arribillaga, Laura; Llópiz, Diana; Dotor, Javier; Lasarte, Juan José; Prieto, Jesús; Borrás‐Cuesta, Francisco; Esteban, Juan Ignacio; Quer, Josep; Vayreda, F.

doi:10.1016/j.antiviral.2007.01.001

Cited by 12 publications

(8 citation statements)

References 54 publications

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“…3A). As opposed to NS3, which does not induce CTL responses without adjuvants [18], EDA-NS3 induced a strong CTL activity against p1073 pulsed T2 cells (Fig. 3B).…”

Section: Eda-ns3 Induces Ns3-specific Ctl In Vivo In the Absence Of Amentioning

confidence: 92%

“…We have previously demonstrated [18,20] that immunization with an antigen plus the adjuvants poly(I:C) and anti-CD40 antibodies synergized on the induction of potent and long lasting T-cell responses against the antigen. Thus, mice were immunized with 2 nmol of EDA-NS3 alone or with anti-CD40, poly(I:C) or with both adjuvants.…”

Section: Combination Of Eda-ns3 With Poly(i:c) and Anti-cd40 Induces mentioning

confidence: 98%

“…with 2 nmol of EDA-NS3 or NS3 proteins. In some cases, they also received 50 lg/mouse of poly(I:C) and 50 lg/mouse of anti-CD40 monoclonal antibody [18]. For DNA immunization, mice received an i.m.…”

Section: Immunization and Measurement Of T-cell Responsesmentioning

confidence: 99%

“…Transient expression of NS3 in the liver was attained by hydrodynamic injection with plasmid gWIZ expressing NS3 as described [18]. Briefly, mice received 20 lg of plasmid diluted in 2 ml of phosphatebuffered saline through the tail vein over 10 seconds using a 27 1/2 g needle.…”

Section: Expression Of Hcv Ns3 In Liver Cellsmentioning

confidence: 99%

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Immunization against hepatitis C virus with a fusion protein containing the extra domain A from fibronectin and the hepatitis C virus NS3 protein

Mansilla

Gorraiz

Martínez

et al. 2009

Journal of Hepatology

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“…3A). As opposed to NS3, which does not induce CTL responses without adjuvants [18], EDA-NS3 induced a strong CTL activity against p1073 pulsed T2 cells (Fig. 3B).…”

Section: Eda-ns3 Induces Ns3-specific Ctl In Vivo In the Absence Of Amentioning

confidence: 92%

Section: Combination Of Eda-ns3 With Poly(i:c) and Anti-cd40 Induces mentioning

confidence: 98%

Section: Immunization and Measurement Of T-cell Responsesmentioning

confidence: 99%

Section: Expression Of Hcv Ns3 In Liver Cellsmentioning

confidence: 99%

See 2 more Smart Citations

Immunization against hepatitis C virus with a fusion protein containing the extra domain A from fibronectin and the hepatitis C virus NS3 protein

Mansilla

Gorraiz

Martínez

et al. 2009

Journal of Hepatology

Self Cite

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“…Evidence from both human and mouse studies suggests that NK cells may also contribute to adaptive immune responses by modulating dendritic cell (DC) function or by producing effector cytokines (7,32). In mice, NK cells were shown to be important for inducing Th1 responses and for early resistance to infection (50). Depletion of NK cells inhibited the generation of Toxoplasma-specific CD8 ϩ T-cell immunity in CD4 Ϫ/Ϫ mice, and adoptive transfer of NK cells restored their CD8…”

mentioning

confidence: 99%

Natural Killer Cells as Novel Helpers in Anti-Herpes Simplex Virus Immune Response

Nandakumar

Woolard

Yuan

et al. 2008

J Virol

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Innate defenses help to eliminate infection, but some of them also play a major role in shaping the magnitude and efficacy of the adaptive immune response. With regard to influencing subsequent adaptive immunity, NK cells aided by dendritic cells may be the most relevant components of the innate reaction to herpes simplex virus (HSV) infection. We confirm that mice lacking or depleted of NK cells are susceptible to HSV-induced lesions. The quantity and quality of CD8 ؉ cytotoxic T lymphocytes generated in the absence of NK cells were diminished, thereby contributing to susceptibility to HSV-induced encephalitis. We demonstrate a novel helper role for NK cells, in that NK cells compensate for the loss of CD4 helper T cells and NK cell supplementation enhances the function of wild type anti-HSV CD8 T cells. In addition, NK cells were able to partially rescue the dysfunctional CD8؉ T cells generated in the absence of CD4 T helper cells, thereby performing a novel rescue function. Hence, NK cells may well be exploited for enhancing and rescuing the T-cell response in situations where the CD4 helper response is affected.

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Enhanced T cell responses against hepatitis C virus by ex vivo targeting of adenoviral particles to dendritic cells

et al. 2011

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Injection of dendritic cells (DCs) presenting viral proteins constitutes a promising approach to stimulate T cell immunity against hepatitis C virus (HCV). Here we describe a strategy to enhance antigen loading and immunostimulatory functions of DCs useful in the preparation of therapeutic vaccines. Incubation of murine DCs with CFm40L, an adapter molecule containing the coxsackie-adenovirus receptor fused to the ecto-domain of murine CD40L-induced DC maturation, produced high amounts of interleukin-12 and up-regulation of molecules associated with T helper 1 responses. Accordingly, targeting of an adenovirus encoding HCV NS3 protein (AdNS3) to DCs with CFm40L strongly enhanced NS3 presentation in vitro, activating interferon-c-producing T cells. Moreover, immunization of mice with these DCs promoted strong CD4 and CD8 T cell responses against HCV NS3. CFh40L, a similar adapter molecule containing human CD40L, enhanced transduction and maturation of human monocyte-derived DCs. Comparison of DCs transduced with AdNS3 and CFh40L from patients with chronic HCV infection and healthy donors revealed similar maturation levels. More importantly, DCs from the patients induced NS3-specific responses when transduced with AdNS3 and CFh40L but not with AdNS3 alone. Conclusion: DCs transduced with AdNS3 and the adapter molecule CFm/h40L exhibit enhanced immunostimulatory functions, induce robust anti-HCV NS3 immunity in animals, and can induce antiviral immune responses in subjects with chronic HCV infection. This strategy may serve as therapeutic vaccination for patients with chronic hepatitis C. (HEPATOLOGY 2011;54:28-37) T he antiviral T cell immunity found in patients with chronic hepatitis C virus (HCV) infection is characterized by its low magnitude and the narrow repertoire of epitopes recognized by T cells. By contrast, individuals who clear the virus have strong and multispecific T cell responses against viral antigens. 1 These results suggest that T cell immunity may be responsible for viral clearance and support the notion that induction of these responses may be advantageous for the treatment of chronic hepatitis C.

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Induction of potent and long-lasting CD4 and CD8 T-cell responses against hepatitis C virus by immunization with viral antigens plus poly(I:C) and anti-CD40

Cited by 12 publications

References 54 publications

Immunization against hepatitis C virus with a fusion protein containing the extra domain A from fibronectin and the hepatitis C virus NS3 protein

Immunization against hepatitis C virus with a fusion protein containing the extra domain A from fibronectin and the hepatitis C virus NS3 protein

Natural Killer Cells as Novel Helpers in Anti-Herpes Simplex Virus Immune Response

Enhanced T cell responses against hepatitis C virus by ex vivo targeting of adenoviral particles to dendritic cells

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