Carey L Shive1, Chelsey J Judge2, Brian Clagett2, Robert C Kalayjian3, Melissa Osborn4, Kenneth E Sherman5, Carl Fichtenbaum5, Rajesh T Gandhi6, Minhee Kang7, Daniel L Popkin8, Scott F Sieg2, Michael M Lederman2, Benigno Rodriguez2, Donald D Anthony9. 1. The Louis Stokes VA Medical Center, Cleveland, OH, USA; Department of Medicine, University Hospitals Medical Center, and the Center for AIDS Research, Case Western Reserve University, Cleveland, OH, USA. 2. Department of Medicine, University Hospitals Medical Center, and the Center for AIDS Research, Case Western Reserve University, Cleveland, OH, USA. 3. The Louis Stokes VA Medical Center, Cleveland, OH, USA; Department of Medicine, MetroHealth Medical Center, Case Western Reserve, Cleveland, OH, USA. 4. Department of Medicine, MetroHealth Medical Center, Case Western Reserve, Cleveland, OH, USA. 5. Department of Medicine, University of Cincinnati Medical Center, Cincinnati, OH, USA. 6. Department of Medicine, Massachusetts General Hospital, Harvard Medical School, USA. 7. Harvard T.H. Chan School of Public Health, Boston, MA, USA. 8. The Louis Stokes VA Medical Center, Cleveland, OH, USA. 9. The Louis Stokes VA Medical Center, Cleveland, OH, USA; Department of Medicine, University Hospitals Medical Center, and the Center for AIDS Research, Case Western Reserve University, Cleveland, OH, USA. Electronic address: dda3@case.edu.
Abstract
BACKGROUND: Chronic hepatitis C virus (HCV) and HIV infections are associated with impaired responses to neo-antigens contained in hepatitis A virus (HAV)/hepatitis B virus (HBV) vaccines, yet responsible mechanisms are unclear. METHODS: ACTG 5232 and CFAR0910 were clinical trials where pre-vaccine levels of plasma IP10, IL-6, sCD163 and sCD14 were measured in viremic HCV- (n = 15) or HIV-infected participants (n = 24) and uninfected controls (n = 10). Accelerated dosing HAV/HBV vaccine and tetanus booster were administered and antibody response was measured at 0, 1, 3, 8, and 24 weeks. RESULTS: Pre-vaccine plasma IP10, IL-6, and sCD14 levels were elevated in both HCV and HIV-infected participants, while sCD163 was also elevated in HCV-infected participants. Pre-immunization tetanus antibody levels were lower in HIV-infected than in uninfected participants, while vaccine induced antibody responses were intact in HCV and HIV-infected participants. After HAV/HBV vaccination, HCV and HIV-infected participants had lower and less durable HAV and HBV antibody responses than uninfected controls. Among HCV-infected participants, pre-vaccine plasma IP10, IL-6, sCD14, and sCD163 levels inversely correlated with HAV, HBV and tetanus antibody responses after vaccine. Low HAV/HBV vaccine responses in HIV-infected participants prohibited assessment of immune correlates. CONCLUSIONS: During HCV and HIV infection markers of systemic inflammation reflect immune dysfunction as demonstrated by poor response to HAV/HBV neo-antigen vaccine. Published by Elsevier Ltd.
BACKGROUND: Chronic hepatitis C virus (HCV) and HIV infections are associated with impaired responses to neo-antigens contained in hepatitis A virus (HAV)/hepatitis B virus (HBV) vaccines, yet responsible mechanisms are unclear. METHODS: ACTG 5232 and CFAR0910 were clinical trials where pre-vaccine levels of plasma IP10, IL-6, sCD163 and sCD14 were measured in viremic HCV- (n = 15) or HIV-infected participants (n = 24) and uninfected controls (n = 10). Accelerated dosing HAV/HBV vaccine and tetanus booster were administered and antibody response was measured at 0, 1, 3, 8, and 24 weeks. RESULTS: Pre-vaccine plasma IP10, IL-6, and sCD14 levels were elevated in both HCV and HIV-infected participants, while sCD163 was also elevated in HCV-infected participants. Pre-immunization tetanus antibody levels were lower in HIV-infected than in uninfected participants, while vaccine induced antibody responses were intact in HCV and HIV-infected participants. After HAV/HBV vaccination, HCV and HIV-infected participants had lower and less durable HAV and HBV antibody responses than uninfected controls. Among HCV-infected participants, pre-vaccine plasma IP10, IL-6, sCD14, and sCD163 levels inversely correlated with HAV, HBV and tetanus antibody responses after vaccine. Low HAV/HBV vaccine responses in HIV-infected participants prohibited assessment of immune correlates. CONCLUSIONS: During HCV and HIV infection markers of systemic inflammation reflect immune dysfunction as demonstrated by poor response to HAV/HBV neo-antigen vaccine. Published by Elsevier Ltd.
Entities:
Keywords:
Cellular immunity; HIV; Hepatitis C; Inflammation; T cell
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