Humoral and cell-mediated immune responses after a booster dose of HBV vaccine in HIV-infected children, adolescents and young adults.

Vania Giacomet,Gian Vincenzo Zuccotti,Pilar Nannini,Daria Trabattoni,Mario Clerici,Michela Masetti,Federica Forlanini,Ravi Jhaveri

doi:10.1371/journal.pone.0192638

Abstract

ObjectiveHBV vaccine induces protective antibodies only in 23–56% of HIV-infected children. The aim of our study is to evaluate the immunologic effects of a booster dose of HBV vaccine in HIV-infected youth.Design53 young HIV-infected patients in whom HBV vaccination did not elicit protective Ab titers were enrolled. All patients were on ART with optimal immunological and viral response.MethodAll patients received a booster dose of HBV vaccine (HBVAXPRO 10 μg i.m.). HBV-specific Ab titer, viral load and CD4+ T cells were measured at baseline (T0), T1, T6 and T12 months. In a subgroup of 16 patients HBV-specific cell mediated immune responses were evaluated at baseline, at T1 and T6.ResultsThe booster dose induced seroconversion in 51% of patients at T1, 57% at T6, and49% at T12; seroconversion rate was significantly correlated with CD4+T cells at T0 and to the CD4 nadir. The booster dose induced HBV-specific cell mediated immunity at T6 mainly in Responders (Rs): Effector Memory CD8+T cells, HBV-specific TNFα-, IFNγ-, granzyme secreting CD8+ T cells and IL2-secreting CD4+ T cells were significantly increased in Rs compared to T0. In Non Responders (NRs), HBV-specific IL2-secreting CD4+ T cells, Central and Effector Memory CD8+ T cells were the only parameters modified at T6.ConclusionsSeroconversion induced by a booster dose of vaccine correlates with the development of T cell immunological memory in HIV-infected patients who did not respond to the standard immunization. Alternate immunization schedules need to be considered in NRs.

Highlights

Chronic viral hepatitis has become a major source of comorbidity in Human Immunodeficiency Virus (HIV) infected populations, with improved survival due to the success of antiretroviral therapy (ART)
The booster dose induced seroconversion in 51% of patients at T1, 57% at T6, and49% at T12; seroconversion rate was significantly correlated with CD4+T cells at T0 and to the CD4 nadir
The booster dose induced HBV-specific cell mediated immunity at T6 mainly in Responders (Rs): Effector Memory CD8+T cells, HBV-specific TNFα, IFNγ, granzyme secreting CD8+ T cells and IL2-secreting CD4+ T cells were significantly increased in Rs compared to T0

Summary

Introduction

Chronic viral hepatitis has become a major source of comorbidity in Human Immunodeficiency Virus (HIV) infected populations, with improved survival due to the success of antiretroviral therapy (ART). HIV complicates the natural course of HBV, resulting in greater levels of HBV viremia, higher rate of HBV reactivation, chronic hepatitis and increased incidence of cirrhosis and liver-related mortality [2,3]. Seroconversion rates and antibodies titers induced by vaccination are known to be sub-optimal in HIV-infected people, compared with the healthy population [4,5,6,7]. It is estimated that between 4% and up to 10% of healthy individuals vaccinated for HBV fail to achieve protection (anti-HBs below 10 IU/ml) as they are considered non-responders. Between 13 to 60% of vaccinated healthy individuals eventually lose their protection as anti-HBs titers tend to decrease over time, a phenomenon known as “waning immunity” [10,11]. The clinical importance of this phenomenon is unclear as it has been suggested that protection may still be maintained despite declining anti-HBs Ab titers [12]

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Conclusion