Immune and viral profile from tolerance to hepatitis B surface antigen clearance: a longitudinal study of vertically hepatitis B virus-infected children on combined therapy

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J Virol. 2011 Mar;85(5):2416-28. Epub 2010 Dec 8.

Immune and viral profile from tolerance to hepatitis B surface antigen

clearance: a longitudinal study of vertically hepatitis B virus-infected

children on combined therapy.

Carey I, D'Antiga L, Bansal S, Longhi MS, Ma Y, Mesa IR, Mieli-Vergani G,

Vergani D.

Institute of Liver Studies, King's College Hospital, London SE5 9RS, UK.

Abstract

The aim of the study was to investigate longitudinally hepatitis B virus

(HBV)-specific T-cell reactivity and viral behavior versus treatment response in

tolerant children during combined antiviral therapy. Twenty-three children with

infancy-acquired hepatitis B (HBeAg(+)) belonging to a published pilot study of

1-year treatment with lamivudine/alpha interferon (IFN-á) were investigated.

Five seroconverted to anti-HBs (responders). Nine were HLA-A2(+) (4 responders

and 5 nonresponders). Mutations within the HBV core gene were determined at

baseline in liver and in serial serum samples by direct sequencing at baseline;

during treatment week 2 (TW2), TW9, TW28, and TW52; and after follow-up week 24

(FUW24) and FUW52. HBV-specific reactivity was evaluated by T-cell proliferation

with 16 HBV core 20-mer overlapping peptides and by HLA-A2-restricted

core(18-27) pentamer staining and CD8(+) IFN-ã enzyme-linked immunospot

(ELISPOT) assay. HBV core-specific T-cell proliferative and CD8 responses were

more vigorous and broader among responders than among nonresponders at TW28 and

TW52, while the number of mutations within HBV core gene immunodominant epitopes

was lower at TW28 and was negatively associated with HBV-specific T-cell

proliferative responses at both time points. The HBV DNA viral load was

negatively associated with HBV-specific T-cell proliferative and CD8 responses

during treatment, especially at TW28. Treatment-induced transition from

immunotolerance to HBV immune control is characterized by the emergence of

efficient virus-specific immune responses capable of restraining mutations and

preventing viral evasion.

PMID: 21147914 [PubMed - indexed for MEDLINE]