Improved cell mediated immune responses after successful re-vaccination of non-responders to the hepatitis B virus surface antigen (HBsAg) vaccine using the combined hepatitis A and B vaccine

Nyström, Jessica; Cardell, Kristina; Björnsdottir, Thora; Frydén, Aril; Hultgren, Catharina; Sällberg, Matti

doi:10.1016/j.vaccine.2008.08.054

Cited by 21 publications

(19 citation statements)

References 23 publications

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“…Given the fact that non-responders also exhibit poor recall responses to tetanus toxoid or Candida , it has been suggested that HBV vaccine non-responsiveness may be due to a defect in HBsAg-reactive T cells 21-24 , regulatory T cells 25 , or in APCs 26, 27 ; this has remained controversial 22-23 . A number of studies have tried to correct non-response by addition of vaccine adjuvants, altered doses, and different vaccine administration routes or strategies 28-31 . These approaches have led to varying degrees of success in healthy subjects, but have been limited in chronically infected individuals.…”

Section: Discussionmentioning

confidence: 99%

Impaired hepatitis B vaccine responses during chronic hepatitis C infection: Involvement of the PD-1 pathway in regulating CD4+ T cell responses

Moorman

Zhang

et al. 2011

Vaccine

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Vaccination for hepatitis B virus (HBV) in the setting of hepatitis C virus (HCV) infection is recommended, but responses to vaccination are blunted when compared to uninfected populations. The mechanism for this failure of immune response in HCV-infected subjects remains unknown but is thought to be a result of lymphocyte dysfunction during chronic viral infection. We have recently demonstrated that PD-1, a novel negative immunomodulator for T cell receptor (TCR) signaling, is involved in T and B lymphocyte dysregulation during chronic HCV infection. In this report, we further investigated the role of the PD-1 pathway in regulation of CD4+ T cell responses to HBV vaccination in HCV-infected individuals. In a prospective HCV infected cohort, a poor response rate to HBV vaccination as assayed by seroconversion was observed in HCV-infected subjects (53%), while a high response rate was observed in healthy or spontaneously HCV-resolved individuals (94%). CD4+ T cell responses to ex vivo stimulations of anti-CD3/CD28 antibodies or hepatitis B surface antigen (HBsAg) were found to be lower in HBV vaccine non-responders compared to those responders in HCV-infected individuals who had received a series of HBV immunizations. PD-1 expression on CD4+ T cells were detected at relatively higher levels in these HBV vaccine non-responders than those who responded, and this was inversely associated with the cell activation status. Importantly, blocking the PD-1 pathway improved T cell activation and proliferation in response to ex vivo HBsAg or anti-CD3/CD28 stimulation in HBV vaccine non-responders. These results suggest that PD-1 signaling may be involved in impairing CD4+ T cell responses to HBV vaccination in subjects with HCV infection, and raise the possibility that blocking this negative signaling pathway might improve success rates of immunization in the setting of chronic viral infection.

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Section: Discussionmentioning

confidence: 99%

Impaired hepatitis B vaccine responses during chronic hepatitis C infection: Involvement of the PD-1 pathway in regulating CD4+ T cell responses

Moorman

Zhang

et al. 2011

Vaccine

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“…To improve the seroconversion of HBV immunization, several approaches - including different administration routes (subcutaneous vs. intradermal injection), higher doses of HBV vaccine (40 µg vs. 20 µg), and adding adjuvants (CPG 7909, levamisole, GM-CSF) - have been tried for nonresponders (Kim et al 2003; Jacques et al 2002; Nystrom et al 2008; Rahman et al 2000; Raman et al 1996). These approaches have led to varying degrees of improvement in healthy subjects, but have had limited success in virally-infected individuals, in part due to a lack of information regarding cellular and molecular mechanisms that inhibit immune responses in this setting.…”

Section: Hbv Vaccine Response Is Blunted In Hcv And/or Hiv-infected Imentioning

confidence: 99%

Immune Exhaustion and Immune Senescence: Two Distinct Pathways for HBV Vaccine Failure During HCV and/or HIV Infection

Yao

Moorman

2013

Arch. Immunol. Ther. Exp.

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Given the shared risk factors for transmission, co-infection of hepatitis B virus (HBV) with hepatitis C virus (HCV) and/or human immunodeficiency virus (HIV) is quite common, and may lead to increases in morbidity and mortality. As such, HBV vaccine is recommended as the primary means to prevent HBV super-infection in HCV- and/or HIV-infected individuals. However, vaccine response (sero-conversion with a hepatitis B surface antibody titer >10 IU/L) in this setting is often blunted, with poor response rates to standard HBV vaccinations in virally infected individuals when compared to the healthy subjects. This phenomenon also occurs to other vaccines in adults, such as pneumococcal and influenza vaccines, in other immunocompromised hosts who are really at risk for opportunistic infections, such as individuals with hemodialysis, transplant, and malignancy. In this review, we summarize the underlying mechanisms involving vaccine failure in these conditions, focusing on immune exhaustion and immune senescence - two distinct signaling pathways regulating cell function and fate. We raise the possibility that blocking these negative signaling pathways might improve success rates of immunizations in the setting of chronic viral infection.

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“…Given the fact that these HBV vaccine non-responders also have poor recall responses to tetanus toxoid or Candida, it has been suggested that HBV vaccine failure may be due to a defect in CD4 + helper T cells [11–14], regulatory T cells [15], or in antigen presenting cells (APCs) [16–17]; this has, however, remained controversial [18–19]. A number of clinical studies have attempted to correct vaccine non-response by adding adjuvants, altering doses, and administering vaccine through different routes or strategies [20– 24]. These approaches have led to varying degrees of improvement in healthy subjects, but have had limited success in virally-infected individuals, in part due to our incomplete understanding of the mechanisms that inhibit vaccine responses in this setting.…”

Section: Introductionmentioning

confidence: 99%

KLRG1 Impairs CD4+ T Cell Responses via p16ink4a and p27kip1 Pathways: Role in Hepatitis B Vaccine Failure in Individuals with Hepatitis C Virus Infection

Shi

Wang

Ren

et al. 2014

The Journal of Immunology

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Co-infection of hepatitis B virus (HBV) with hepatitis C virus (HCV) is quite common, leading to an increase in morbidity and mortality. As such, HBV vaccination is recommended in HCV-infected individuals. HBV vaccine responses in HCV-infected individuals, however, are often blunted when compared to uninfected populations. The mechanism for this failure of vaccine response in HCV-infected subjects remains unclear. In this study, we investigated the expression and function of an inhibitory receptor, killer cell lectin-like receptor subfamily G member 1 (KLRG1), in regulation of CD4+ T cells and HBV vaccine responses during HCV infection. We demonstrated that KLRG1 was over-expressed on CD4+ T cells from HCV-infected, HBV vaccine non-responders (HBV-NR) compared to those responders (HBV-R). The capacity of CD4+ T cell to proliferate and secrete IL-2 cytokine was inversely associated with the level of KLRG1 expression. Importantly, blocking KLRG1 signaling resulted in a significant improvement of CD4+ T cell proliferation and IL-2 production in HCV-infected, HBV-NR in response to T cell receptor (TCR) stimulation. Moreover, blockade of KLRG1 increased the phosphorylation of Akt (Ser473) and decreased the expression of cell cycle inhibitors p16ink4a and p27kip1, which subsequently enhanced CDK 2 and cyclin E expressions. These results suggest that the KLRG1 pathway impairs CD4+ T cell responses to neo-antigen and induces a state of immune senescence in individuals with HCV infection, raising the possibility that blocking this negative signaling pathway might improve HBV vaccine responses in the setting of chronic viral infection.

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Improved cell mediated immune responses after successful re-vaccination of non-responders to the hepatitis B virus surface antigen (HBsAg) vaccine using the combined hepatitis A and B vaccine

Cited by 21 publications

References 23 publications

Impaired hepatitis B vaccine responses during chronic hepatitis C infection: Involvement of the PD-1 pathway in regulating CD4+ T cell responses

Impaired hepatitis B vaccine responses during chronic hepatitis C infection: Involvement of the PD-1 pathway in regulating CD4+ T cell responses

Immune Exhaustion and Immune Senescence: Two Distinct Pathways for HBV Vaccine Failure During HCV and/or HIV Infection

KLRG1 Impairs CD4+ T Cell Responses via p16ink4a and p27kip1 Pathways: Role in Hepatitis B Vaccine Failure in Individuals with Hepatitis C Virus Infection

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