Cellular immunity in children with successful immunoprophylactic treatment for mother-to-child transmission of hepatitis B virus

Abstract

BackgroundThe administration of hepatitis B immunoglobulin followed by hepatitis B vaccine can result in a protective efficacy of almost 90% in mother-to-child transmission of hepatitis B virus (HBV). However, little is known about immunity against HBV infection in children after immunoprophylactic treatment. We tried to assess the association between T-cell responses and viremia in children after successful prophylactic treatment.MethodsThirteen children and their 8 HBV carrier mothers (8 families), who were positive for human leukocyte antigen (HLA)-A24, were enrolled in this study. All of the 13 children received immunoprophylactic treatment and became negative for hepatitis B surface antigen (HBsAg) after birth. HBV-specific cytotoxic T lymphocyte (CTL) responses were evaluated using IFNγ - enzyme-linked immunosorbent spot (ELISPOT) and major histocompatibility complex class I peptide pentamer assays. Serum HBV DNA was measured by real-time PCR.ResultsSignificant HBV-specific T-cell responses were detected in 2 (15%) of the 13 children by ELISPOT. However, the frequency of HLA-A24-HBV-specific CTLs was very low in both HBV carrier mothers and children using pentamers. Of the 13 children, 4 (31%) were positive for serum HBV DNA. However, the levels of serum HBV DNA were 100 copies/ml or less. One of the 2 children in whom significant HBV-specific CTL responses were detectable was positive for serum HBV DNA.ConclusionsHBV core and polymerase-specific T-cell responses were detected and a low-dose viremia was observed in children after successful immunoprophylaxis treatment. Although the presence of viremia was not related to HBV-specific T-cell responses, CTLs might play a role in the control of HBV infection in children born to HBsAg-positive mothers after immunoprophylactic treatment.

HBV viremia in newborns of HBsAg(+) predominantly Caucasian HBeAg(−) mothers

“…24 Such T-cell responses, although not related to detectable viremia, are due to viral exposure. Detection of such responses at birth supports the hypothesis of in utero exposure.…”

“…Moreover, HBV viremia following successful immunoprophylaxis has been reported even among older children, born to either HBeAg(+) or HBeAg(−) mothers in endemic areas, which may have significant implications and needs to be confirmed. 15,16,20,24 High maternal viremia and HBeAg(+) status are identifiable risk factors for HBV viremia and infection despite immunoprophylaxis and therefore have been associated with the occurrence of in utero HBV transmission. [11][12][13][14][25][26][27][28][29] In our study, children of HBeAg(−) mothers had a similar incidence of neonatal viremia probably due to the small number of HBeAg(+) mothers studied.…”

The immune tolerant phase of chronic HBV infection: new perspectives on an old concept

“…20 Furthermore, a better analysis of data generated in natural HBV infection reveals that a proportion of neonates exposed to HBV at birth, mount a HBV-specific T-cell response. For example, two independent studies performed in HBsAg-negative children born to HBV-positive mothers 21,22 have demonstrated the presence of core and polymerase-specific T cells. Neonates of HBV 1 mothers have also been shown to have minimal or normal dendritic cell functions.…”

Biodegradable polylactide microspheres enhance specific immune response induced by Hepatitis B surface antigen

“…2,16,18,19 HBV-specific T-cell responses, especially CTLs, play a role in the control of HBV infection in children born to HBsAg-positive mothers after immunoprophylactic treatment. 20 The aim of the present study was to evaluate the immune effects of a new microsphere vaccine, which could provide an effective means to combat chronic hepatitis B infection. Since the adsorbed antigen is much easier to release from the surface of the microsphere rather than from encapsulated microspheres used in controlled-release formulations, the microsphere vaccine formulated in this study could evoke a much quicker immune response.…”