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.
Department of Medicine, University Hospitals Medical Center, and the Center for AIDS Research, Case Western Reserve University, Cleveland, OH, USA.
Vaccine. 2018 Jan 25;36(4):453-460. doi: 10.1016/j.vaccine.2017.12.018. Epub 2017 Dec 16.
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.
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.
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.
During HCV and HIV infection markers of systemic inflammation reflect immune dysfunction as demonstrated by poor response to HAV/HBV neo-antigen vaccine.
慢性丙型肝炎病毒（HCV）和 HIV 感染与甲型肝炎病毒（HAV）/乙型肝炎病毒（HBV）疫苗中包含的新抗原的应答受损有关，但尚不清楚其相关机制。
ACTG5232 和 CFAR0910 是两项临床试验，其中对病毒血症 HCV 感染（n=15）或 HIV 感染参与者（n=24）和未感染对照者（n=10）的血浆 IP10、IL-6、sCD163 和 sCD14 的预疫苗水平进行了测量。给予加速剂量的 HAV/HBV 疫苗和破伤风加强针，并在 0、1、3、8 和 24 周时测量抗体应答。
HCV 和 HIV 感染参与者的血浆 IP10、IL-6 和 sCD14 水平在预疫苗时升高，而 HCV 感染参与者的 sCD163 水平也升高。HIV 感染参与者的破伤风抗体水平低于未感染参与者，而 HCV 和 HIV 感染参与者的疫苗诱导抗体应答完整。接种 HAV/HBV 疫苗后，HCV 和 HIV 感染参与者的 HAV 和 HBV 抗体应答较低且持续时间较短，与未感染对照者相比。在 HCV 感染参与者中，疫苗前血浆 IP10、IL-6、sCD14 和 sCD163 水平与疫苗后 HAV、HBV 和破伤风抗体应答呈负相关。HIV 感染参与者的 HAV/HBV 疫苗低应答阻止了对免疫相关性的评估。
在 HCV 和 HIV 感染期间，全身性炎症标志物反映了免疫功能障碍，表现为对 HAV/HBV 新抗原疫苗的应答不良。
