Last data update: Jun 03, 2024. (Total: 46935 publications since 2009)
Records 1-5 (of 5 Records) |
Query Trace: Rybczynska J [original query] |
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CD4+ T cells are not required for suppression of hepatitis B virus replication in the liver of vaccinated chimpanzees
Rybczynska J , Campbell K , Kamili S , Locarnini S , Krawczynski K , Walker CM . J Infect Dis 2015 213 (1) 49-56 Humans vaccinated with hepatitis B virus (HBV) surface antigen (HBsAg) sometimes develop humoral and cellular immunity to HBV proteins such as core and polymerase that are not vaccine components, providing indirect evidence that vaccine-induced immunity is not sterilizing. We previously described CD4+ T-cell immunity against HBsAg and polymerase in chimpanzees after vaccination and HBV challenge. Here, vaccinated chimpanzees with protective levels of anti-HBsAg antibodies were rechallenged with HBV after antibody-mediated CD4+ T-cell depletion. HBV DNA was detected in liver for at least 3 months after rechallenge, but virus replication was suppressed, as revealed by the absence of HBV DNA and HBsAg in serum. These observations provide direct virological evidence for nonsterilizing immunity in individuals with anti-HBsAg antibodies and are consistent with translation of HBV proteins to prime immune responses. They also indicate that CD4+ T cells were not required for suppression of HBV replication in previously vaccinated individuals. |
Hepatitis B vaccine immunogenicity among adults vaccinated during an outbreak response in an assisted living facility-Virginia, 2010
Bender TJ , Sharapov U , Utah O , Xing J , Hu D , Rybczynska J , Drobeniuc J , Kamili S , Spradling PR , Moorman AC . Vaccine 2013 32 (7) 852-6 BACKGROUND: Failure to adhere to infection control guidelines, especially during assisted monitoring of blood glucose, has caused multiple hepatitis B outbreaks in assisted living facilities (ALFs). In conjunction with the response to such an outbreak at an ALF ("Facility X") where most residents had neuropsychiatric disorders, we evaluated seroprotection rates conferred by hepatitis B vaccine and assessed the influence of demographic factors on vaccine response. METHODS: Residents were screened for hepatitis B and C infection, and those susceptible were vaccinated against hepatitis A and hepatitis B with one dose of TWINRIX (GSK) given at 0, 1, and 7 months. Blood samples were collected 1-2 months after receipt of the third vaccine dose to test for antibody to hepatitis B surface antigen (anti-HBs). RESULTS: Of the 27 residents who had post-vaccination blood specimens collected, 22 (81%) achieved anti-HBs concentrations ≥10mIU/mL. Neither age nor neuropsychiatric comorbidity was significant determinants of seroprotection. Geometric mean concentration was lower among residents aged 60-74 years (74.3mIU/mL) than among residents aged 46-59 years (105.3mIU/mL) but highest among residents aged ≥75 years (122.5mIU/mL). The effect of diabetes on vaccination response could not be examined because 16/17 (94%) diabetic residents had HBV infection by the time of investigation. CONCLUSIONS: Adult vaccine recipients of all ages, even those over 60 years of age, demonstrated a robust capacity for achieving hepatitis B seroprotection in response to the combined hepatitis A/hepatitis B vaccine. The role for vaccination in interrupting HBV transmission during an outbreak remains unclear, but concerns about age-related response to hepatitis B vaccine may be insufficient to justify foregoing vaccination of susceptible residents of ALFs. |
Immunopathogenesis of hepatitis E virus infection
Wedemeyer H , Rybczynska J , Pischke S , Krawczynski K . Semin Liver Dis 2013 33 (1) 71-8 The course of hepatitis E virus infection (HEV) can vary substantially between different individuals. Although most infections take a clinically silent asymptomatic course, a few patients may develop severe hepatitis that can progress to fulminant hepatic failure. In addition, cases of chronic hepatitis E have been described in immunosuppressed patients. The detailed mechanisms leading to different clinical outcomes of HEV infection are only partially understood. Both viral factors including the HEV genotype and the dose of the infectious inoculum, as well as host factors such as stage of liver disease, pregnancy or distinct genetic polymorphisms determine the course of HEV infection. Recent studies were able to associate T-cell responses, activation of the interferon system and viral evolution with severity or chronicity of hepatitis E. We here summarize the emerging data on the immunopathogenesis of HEV infection. |
Both innate and adaptive immunity mediate protective immunity against hepatitis C virus infection in chimpanzees
Barth H , Rybczynska J , Patient R , Choi Y , Sapp RK , Baumert TF , Krawczynski K , Liang TJ . Hepatology 2011 54 (4) 1135-48 Understanding the immunological correlates associated with protective immunity following hepatitis C virus (HCV) reexposure is a prerequisite for the design of effective HCV vaccines and immunotherapeutics. In this study we performed a comprehensive analysis of innate and adaptive immunity following HCV reexposure of two chimpanzees that had previously recovered from HCV-JFH1 infection. One of the chimpanzees, CH10274, became protected from active viremia by repeated challenges with homologous HCV-JFH1 and developed neutralizing antibodies, but was later infected with high-level viremia by a heterologous challenge with the HCV H77 virus that persisted for more than 1 year. The other chimpanzee, CH10273, was protected from a similar, heterologous H77 challenge without any evidence of neutralizing antibodies. Peripheral HCV-specific T-cell responses were present in both chimpanzees after challenges and, interestingly, the overall magnitude of response was lower in uninfected CH10273, which, however, exhibited a more robust CD8+ T-cell response. CH10273 showed higher hepatic expression of CD8 and CD56 (natural killer) markers than CH10274 did shortly after inoculation with H77. The heightened T-cell response was associated with an enhanced hepatic production of interferons (both type I and II) and interferon-stimulated genes (ISGs) in CH10273. Therefore, protection or clearance of HCV reinfection upon heterologous rechallenge depends on the activation of both intrahepatic innate and cellular immune responses. Furthermore, our results suggest that serum neutralizing antibodies may contribute to early control of viral replication and spread after homologous HCV rechallenges but may not be sufficient for a long-term protective immunity. CONCLUSION: Our study shows that protective immunity against HCV reinfection is orchestrated by a complex network of innate and adaptive immune responses. (HEPATOLOGY 2011;). |
Pathogenetic elements of hepatitis E and animal models of HEV infection
Krawczynski K , Meng XJ , Rybczynska J . Virus Res 2011 161 (1) 78-83 The pathogenesis of HEV infection responsible for liver pathology and clinical disease is not well understood. The main target for the virus is hepatocyte, where it replicates and is released to bile and gastrointestinal tract. Viremia is regularly seen during the virus replication. The exact mechanism of hepatocytic death is uncertain. In experimentally infected non-human primates, the peak of liver lesions, measured by alanine aminotransferase activity elevation, is concordant with the virus disappearance from stool at the time of dynamic humoral immune response; the role of cellular immunity has not been research adequately, especially HEV-specific immune response in the liver. Non-human primates (chimpanzees, rhesus and cynomolgus macaques) are most widely used animal models for the study of HEV infection, its pathogenesis and vaccine trials. Several other animal models including pigs, rabbits and chickens have recently been established for the study of various aspects of HEV infection. Infectivity studies in susceptible primates were of significance in molecular studies of the virus itself. Preclinical vaccine trials with the use of various recombinant HEV capsid proteins and viral DNA established basic platform for formulation of HEV vaccine applied in HEV-endemic regions (China, Nepal). |
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