T follicular helper cells and antibody response to Hepatitis B virus vaccine in HIV-1 infected children receiving ART

Bekele, Yonas; Yibeltal, Desalegn; Bobosha, Kidist; Andargie, Temesgen E.; Lemma, Mahlet; Gebre, Meseret; Mekonnen, Eyasu; Habtewold, Abiy; Nilsson, Anna; Aseffa, Abraham; Howe, Rawleigh; Chiodi, Francesca

doi:10.1038/s41598-017-09165-6

Cited by 14 publications

(11 citation statements)

References 45 publications

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“…Additionally, analysis of antigen specific Tfh was also not done here. Vaccine antigen-specific Tfh can be detected in germinal center and periphery, nevertheless peripheral antigen specific Tfh detection during chronic infection is difficult 30 , 31 . We were not able to reliably detect HBV antigen specific cytokine production in peripheral Tfh from CHB patients.…”

Section: Discussionmentioning

confidence: 99%

HBV induces inhibitory FcRL receptor on B cells and dysregulates B cell-T follicular helper cell axis

Poonia

Ayithan

Nandi

et al. 2018

Sci Rep

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Spontaneous or treatment induced seroconversion in chronic HBV infection is rare and generation of anti-HBs antibodies is the current goal of HBV therapeutics. Here we investigated B and follicular T helper (Tfh) cell defects that persist in HBV infection despite long-term nucleos(t)ide analog (NUC) treatment and possible mechanisms behind them. RNA sequencing revealed that patient B cells have upregulated expression of multiple inhibitory receptors including members of FcRL family and downregulation of genes involved in antigen presentation. An expansion of atypical memory CD19+CD10−CD27−CD21− subset of B cells, that express high levels of FcRL5, is persistently present in patients. HBs antigen specific IgG response is concentrated in classical memory and not in atypical memory subset, confirming dysfunction of this subset. Activated Tfh, which expressed excessive CD40L upon polyclonal stimulation, were present in patients. Incubation of B cells from healthy individuals with HBV core (HBc) or CD40L resulted in induction of inhibitory receptors FcRL4, FcRL5 and PD-1 on CD19+ cells and resulted in altered B cell phenotypes. Mechanistically, HBc binds B cells and causes proliferation specifically of FcRL5+ B cell subset. Our results provide evidence that HBV directly causes upregulation of inhibitory pathways in B cells resulting in an accumulation of atypical B cells that lack anti-HBs function.

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Section: Discussionmentioning

confidence: 99%

HBV induces inhibitory FcRL receptor on B cells and dysregulates B cell-T follicular helper cell axis

Poonia

Ayithan

Nandi

et al. 2018

Sci Rep

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“…Others, also reported higher levels of IFN‐γ among patients with ASD compared with controls . Second, Bekele et al showed that HBV‐infected mice and blood from patients with chronic HBV infection contained follicular helper T cells (Tfh cells). These cells consisted of certain phenotypes for producing IFN‐γ, interleukin 2, interleukin 4, and interleukin 21 upon stimulation with HBsAg .…”

Section: Discussionmentioning

confidence: 98%

“…Second, Bekele et al showed that HBV‐infected mice and blood from patients with chronic HBV infection contained follicular helper T cells (Tfh cells). These cells consisted of certain phenotypes for producing IFN‐γ, interleukin 2, interleukin 4, and interleukin 21 upon stimulation with HBsAg . Wang et al also showed that response to HBsAg was blocked by regulatory T cells (Treg cells).…”

Section: Discussionmentioning

confidence: 99%

Measurement of serum hepatitis B surface antibody levels in Iranian autistic children and evaluation of immunological memory after booster dose injection in comparison with controls

Barfi

Chimeh

Pouretemad

et al. 2019

Journal of Medical Virology

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Background: Responsiveness to hepatitis B vaccine among patients with autism spectrum disorders (ASD) has not been evaluated worldwide. We aimed to determine the anti-HBs antibody duration in autistic and healthy children few years after primary vaccination and evaluate their immunological memory against hepatitis B virus (HBV) vaccine with booster dose administration.Methods: One hundred seven and 147 HBsAg-negative children from ASD and normal population were recruited, respectively. HBV seromarkers (HBc-Ab, HBsAg, and HBs-Ab) were assessed and subsequently, molecular tests were used on all the subjects. A booster dose of vaccine was injected for those who showed low levels (<10 mIU/mL) of anti-HBs and their antibody levels was measured 4 weeks later.Results: The mean ages of ASD and control groups were 7.14 ± 2.42 and 8.68 ± 1.96, respectively. Seven (6.5%) of the ASD group were positive for anti-HBc and one child was positive for occult hepatitis B infection (HBsAg negative, HBV DNA positive). In ASD, 54 (50.4%) and 53 (49.6%) had adequate (>10 mIU/mL) and low anti-HBs levels, respectively. Among control group, 74 (50.4%) and 73 (49.6%) had sufficient and low antibody levels, respectively. After injection of a booster dose for all children with low antibody, 100% of ASD and 92% (59 of 64) of control pupils contained >10 mIU/mL of antibody, respectively. In both the groups, the HBs-Ab titer increased similarly in response to the booster injection (P < 0.05).Conclusion: Despite previous investigations regarding immune impairment in individuals with autism, the immune system of these individuals was able to manage the hepatitis B vaccine challenge. K E Y W O R D S autism, hepatitis B vaccine, hepatitis B virus J Med Virol. 2019;91:1272-1278. wileyonlinelibrary.com/journal/jmv 1272 |

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“…ARV + ) were significantly lower than their unexposed, uninfected counterparts. Several studies have reported reduced childhood HBV vaccine mediated responses in HEI children relative to their negative counterparts [52][53][54][55][56]. However, childhood HBV vaccine mediated responses were significantly higher in HEI.ARV + children than their untreated counterparts (HEI.ARV -).…”

Section: Discussionmentioning

confidence: 99%

Antibody Responses Specific to Hepatitis B Virus Vaccine in Children Exposed InUtero to Antiretroviral Therapy

2019

JCEI

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The use of antiretroviral (ARV) has been one of the most effective means of preventing vertical transmission of the human immunodeficiency virus (HIV) to exposed children born of HIV infected mothers. Nevertheless, responses to childhood vaccination against Hepatitis B virus (HBV) infections remain suboptimal in HIV exposed uninfected children irrespective of maternal ARV prophylaxis. In a cross-sectional study we have assessed the impact of in-utero exposure to ARV on paediatric HBV vaccination. Anti-HBV surface antigen specific antibodies (anti-HBs abs) were measured in plasma specimens from 44 healthy children unexposed to both HIV and ARV (HU), 25 HIV-exposed uninfected children naïve to intrauterine exposure to ARV (HEU.AR -), 29 ARV and HIV-exposed uninfected children during pregnancy (HEU.ARV + ), 50 children vertically infected with HIV but naïve to intrauterine exposure to ARV (HEI.ARV -) and 22 children vertically infected with HIV with in utero exposure to ARV (HEI.ARV + ). The protective seroconversion rate after childhood HBV vaccination (anti-HBs ≥10 mUI/ml) among HEU.ARV + children (58%) was significantly lower relative to both HEU.ARVc -(100%, P=0.0010) and the healthy unexposed children (92 %, P=0.0069). Similarly, HEI.ARV + children also had significantly lower anti-HBs IgM antibody responses when compared to both HU (p=0.0003) and HEI.ARV -(0.0001) children respectively. Thus in-utero exposure to ARV probably contributes in reducing HBV vaccine antibody response rate in both HIV exposed uninfected and vertically infected children after childhood vaccination. Nevertheless, the overall impact of ARV was to improve anti-HBs IgG responses in HIV infected children suggesting a possible role in immune reconstitution leading to improved IgG antibody responses.

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T follicular helper cells and antibody response to Hepatitis B virus vaccine in HIV-1 infected children receiving ART

Cited by 14 publications

References 45 publications

HBV induces inhibitory FcRL receptor on B cells and dysregulates B cell-T follicular helper cell axis

HBV induces inhibitory FcRL receptor on B cells and dysregulates B cell-T follicular helper cell axis

Measurement of serum hepatitis B surface antibody levels in Iranian autistic children and evaluation of immunological memory after booster dose injection in comparison with controls

Antibody Responses Specific to Hepatitis B Virus Vaccine in Children Exposed InUtero to Antiretroviral Therapy

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