Immunological response after a booster dose of HBV vaccine in HIV-infected youth

Background: Three doses of vaccine against HBV induce the production of protective antibody (Ab) levels (>10 IU/mL) in 95-100 % of healthy children but in only 23-56% of HIV-infected children. Ab titer elicited by vaccination decreases over time in both populations with a faster slope observed in HIV+. This decline protection against HBV is known to last almost three decades after vaccination in immunocompetent children, these data are limited in HIV+ children Methods: 53 HIV+ patients (aged 8-25 years old) in whom HBV vaccination according the Italian schedule did not elicit the generation of protective Ab titers were enrolled in the study at Paediatric Infectious Diseases Unit, L. Sacco Hospital, University of Milan. All patients had undergone ART for at least 1 year; HIV viral load was undetectable in all of them, median CD4+ count 718 mm3. All patients received a booster dose of HBV vaccine (HBVAXPRO 10 micrograms i.m.). HBV-specific Ab titer, viral load and CD4 + were measured in all subjects at baseline (T0), at 1 (T1), 6 (T6) and 12 (T12) months after the booster dose. In a subgroup of 16 patients HBV-specific cell mediated immune (CMI) responses were evaluated at baseline and at T6. Results: The booster HBV vaccine dose resulted in a seroconversion rate (anti-HBs ≥ 10 IU/mL) in 51% of patients at T1, 57% at T6 and 49% at T12; seroconversion rate was significantly correlated with CD4+T lymphocyte counts at T0 and to CD4 nadir (p<0.05). HIV viral load was undetectable at each time. CMI responses were evaluated in 11 responders (HBsAb >10 IU/mL) and 5 non-responders (HBsAb <10 IU/mL). Upregulation of HBV-specific CMI compared to baseline values was observed at T6 in responders alone. Memory (p= 0.007), Effector Memory (p= 0.003), TNF- (p= 0.041), IFN- (p= 0.004), and granzyme-secreting CD8+ T cells (p= 0.003), Central Memory (p= 0.005) and IL2-secreting CD4+ T cells (p= 0.015) were significantly increased in responders compared to baseline values. Activated CD8+CD38+CD45RO+ T cells (p= 0.004) were significantly reduced as well at T6 in these individuals. No significant differences were observed when T0 and T6 data were compared in non responders. Conclusions: In HIV+ patients no responding to the standard HBV immunization protocol, seroconversion induced by a booster dose of vaccine (Ab titers <10 IU/mL) correlates with the development of T cell immunological memory. Alternate immunization schedules should be designed for those individuals who don't respond even to a booster dose of vaccine