anti-HBs Response Research Articles

Assessment of the anti-HBs antibody response in Beninese infants following 4 doses of HBV vaccine, including administration at birth, compared to the standard 3 doses regime; a cross-sectional survey

Hepatitis B virus (HBV) infection remains one of the major neglected health issues worldwide. In sub-Saharan Africa (SSA), HBV endemicity is high, with more than 8% of the population being chronic HBV carriers. Recently, WHO recommended that all infants should receive their first dose of the HBV vaccine as soon as possible after birth. Unfortunately, the incorporation of a birth dose of HBV in the expanded programme immunization (EPI) has not occurred in the majority of countries in SSA. From April to September 2017, a cross-sectional survey was conducted in two vaccine units located in southern Benin. We assessed the sustained anti-HBs antibody response in infants induced by a standard scheme of 3 doses of HBV vaccination (6, 10, 14 weeks) in comparison to a scheme of 4 doses with a birth dose included (0, 6, 10, 14 weeks). Blood samples were systematically collected in the first 140 children aged 9 months and their mothers who had consented to participate for the detection of HBs antigen and the quantification of anti-HBs antibodies. The prevalence of HBV infection among infants and mothers was 2.2% and 7.1%, respectively. Infants who received 4 doses of HBV vaccine had a significantly higher level of anti-HBs antibody than those who received 3 doses of vaccine (557.9 UI/L vs. 386.9 UI/L, respectively, P = 0.03). We also showed that the scheme of 4 doses was associated with a significantly higher sustained protective response in comparison to the scheme of 3 doses (aOR 2.49, 95% CI 1.03–6.03, P = 0.04). This result provides further evidence of the importance of administering HBV vaccine at birth, but also highlights the importance for the prevention of vertical transmissions. Additional studies are needed to better establish the cost-effectiveness of such a 4 doses immunization strategy before implementing the HBV vaccination at birth in the EPI.

Outcome of Repeated Vaccination to Hepatitis B Virus in Patients Failing to Respond to Vaccination Following Allogeneic Hematopoietic Stem Cell Transplantation (HSCT): If at First You Don't Succeed, Try Try Again

Background: Recipient immunity is compromised after HSCT, obligating patients (pts) to take prophylactic antimicrobial and antiviral agents and to be reimmunized to viral and bacterial pathogens. Hepatitis B virus (HBV) infection is a major public health problem, with about 30% of the world population having serological evidence of current or past HBV infection. HBV vaccination post-HSCT is imperative in these pts, as most lose protective HBV surface antibodies (anti-HBs) following conditioning, placing them at high risk for HBV reactivation. Guidelines recommend delaying vaccination (including HBV) for 6-12 months following transplantation to allow for cellular and humoral immune recovery. Even with delaying vaccination, immunosuppression, graft-versus-host disease (GVHD), and delayed immune reconstitution hinder the effectiveness of vaccines. The efficacy of HBV vaccination is not well defined in pts on immunosuppressive therapy (IST) and/or in those with GVHD. Further, little data exists on the efficacy of HBV revaccination in pts failing to respond to the 1st vaccination series. We studied factors impacting the success of vaccination in pts undergoing one to four HBV vaccination series after HSCT. Methods: This single-center, retrospective study evaluated the effectiveness of HBV vaccine in HSCT pts by assessing protective antibody generation after vaccination. Fifty-two pts (25 female, 27 male) who received at least one 3-dose HBV vaccination series post-HSCT and who had evaluable post-vaccine anti-HBs titers were included in the analysis. Pts with negative or indeterminate anti-HBs titers following the first vaccine series were eligible to receive one or more additional series of HBV vaccinations. All pts were treated with cyclophosphamide and fludarabine based conditioning (± anti-thymocyte globulin) and received GVHD prophylaxis with either cyclosporine/tacrolimus with or without mycophenolate mofetil. The vaccine response rate over a series of vaccinations was estimated by Kaplan-Meier methods. The development of response after the first vaccination was correlated with patient baseline and post-HSCT factors including pretransplant HBV titers, vaccination time post-transplant, use of rituximab and IST and absolute lymphocyte count (ALC), CD4, and CD8 cell counts and history of acute or chronic GVHD. Results: The studied cohort included 52 HSCT pts with a median age of 22 years (range 7-62) and a variety of diagnoses (38 aplastic anemia, 6 myelodysplastic syndrome and 8 hematological malignancies). Thirty-five pts underwent HSCT from an HLA-matched donor and 17 pts received a combined haploidentical and umbilical cord blood transplant. The median time to first HBV vaccination was 12 months (8-37) post-HSCT. Following the 1st vaccination series; 19, 4 and 2 pts received a 2nd, 3rd and 4th vaccination series. The estimated cumulative anti-HBs response rates were 51.9%, 82.3%, 91.1% and 100% for the four vaccination series, respectively (Figure). A logistic regression analysis revealed: a) Pts who achieved a response after the initial vaccination series had higher CD4 counts compared to those who failed to mount a response (median CD4 count 450 vs. 300/μL, P= 0.024, Figure); b) Pts without a history of acute GVHD (n=23) were significantly more likely to respond to the 1st vaccination series compared to those with acute GVHD (n=29) (response: 69.6% vs 37.9%, P= 0.029). Other factors included in this analysis were not found to be correlated with the anti-HBs response after the initial vaccination series. Conclusions: Multiple rounds of HBV vaccination may be required before a protective antibody response is achieved. After the first vaccination series, only 51.9% of pts achieved a response, with lower pre-vaccination CD4 counts and a prior history of acute GVHD being negatively associated with vaccine success. Remarkably, with continued vaccination attempts (up to four vaccination series), all evaluable pts ultimately developed a protective anti-HBs response. Figure Disclosures Shalabi: GlaxoSmithKline: Other: Spouse is employed by GSK Pharma.

Toward a Functional Cure for Hepatitis B: The Rationale and Challenges for Therapeutic Targeting of the B Cell Immune Response.

The central role of the cellular immune response in the control and clearance of the hepatitis B virus (HBV) infection has been well-established. The contribution of humoral immunity, including B cell and antibody responses against HBV, has been investigated for a long time but has attracted increasing attention again in recent years. The anti-HBs antibody was first recognized as a marker of protective immunity after the acute resolution of the HBV infection (or vaccination) and is now defined as a biomarker for the functional cure of chronic hepatitis B (CHB). In this way, therapies targeting HBV-specific B cells and the induction of an anti-HBs antibody response are essential elements of a rational strategy to terminate chronic HBV infection. However, a high load of HBsAg in the blood, which has been proposed to induce antigen-specific immune tolerance, represents a major obstacle to curing CHB. Long-term antiviral treatment by nucleoside analogs, by targeting viral translation by siRNA, by inhibiting HBsAg release via nucleic acid polymers, or by neutralizing HBsAg via specific antibodies could potentially reduce the HBsAg load in CHB patients. A combined strategy including a reduction of the HBsAg load via the above treatments and the therapeutic targeting of B cells by vaccination may induce the appearance of anti-HBs antibodies and lead to a functional cure of CHB.

Induction of peripheral blood T follicular helper cells expressing ICOS correlates with antibody response to hepatitis B vaccination

T follicular helper (TFH) cells, a critical subset of CD4+ T cells, provide help to B cells during the procession of the humoral immune response in the germinal center (GC) and extrafollicular sites. CXCR5+ CD4+ T cells in human circulating blood, referred to herein as peripheral TFH (pTFH) cells, share phenotypes and functional properties with TFH cells in GC. Hepatitis B vaccine protects about 60% of the chronic hepatitis C patients from hepatitis B. The immunological bases that lead to the induction of protective antibody response is not well understood. In the present study, the pTFH cells subsets were determined in 18 healthy controls (anti-HBs ≥ 100 mIU/mL; HC), 21 nonresponders (anti-HBs < 10 mIU/mL; NR), and 23 weak responders (10 mIU/mL ≤ anti-HBs < 100 mIU/mL; WR) of chronic hepatitis patients upon routine hepatitis B vaccination. Though the frequency of the pTFH cell was equivalent in HC, WR, and NR, ICOS+ pTFH cells in HC underwent expansion with increased IL-21 secretion and production of serum anti-HBs response at 4 weeks after a full course of hepatitis B vaccination. These changes were not shown in both NR and WR. Analysis of ICOS+ pTFH cells represents a novel cellular determinant of the hepatitis B vaccine-induced humoral immune response, which may have relevance for design of hepatitis B vaccine.

Expression and detection of anti-HBs antibodies after hepatitis B virus infection or vaccination in the context of protective immunity.

Anti-HBs antibodies develop after natural infection with hepatitis B virus (HBV) or vaccination against this virus, as a result of activation of the human immune system by the HBV surface antigen (HBsAg). Anti-HBs-positive individuals are immunologically competent against HBV infection. This immunity is determined by the antibody levels in the bloodstream after resolution of natural infection or after vaccination. Anti-HBs antibody levels have been observed to decrease to below the protective level years after natural infection or vaccination, and there is reason to doubt that protective immunity to HBV is maintained after that. Factors that affect the maintenance of the anti-HBs antibody level in the bloodstream have been reported. Maintenance of immunity to HBV has been reported in anti-HBs negative individuals and those with detectable but low levels after natural infection or after vaccination. On the other hand, detection of anti-HBs antibodies without protective activity has also been observed. The presence or absence of anti-HBs antibodies in the context of HBV immunity has been the subject of extensive discussion and clinical, laboratory and epidemiological interest. These three scenarios of the anti-HBs response are discussed in this review article.

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

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.

A unique B cell epitope-based particulate vaccine shows effective suppression of hepatitis B surface antigen in mice

ObjectiveThis study aimed to develop a novel therapeutic vaccine based on a unique B cell epitope and investigate its therapeutic potential against chronic hepatitis B (CHB) in animal models.MethodsA series...

Comparison of antibody response to hepatitis B vaccination in infants with positive or negative maternal hepatitis B e antigen (HBeAg) in cord blood: implication for the role of HBeAg as an immunotolerogen

ABSTRACT Hepatitis B e antigen (HBeAg) has been considered to cause immunotolerance to hepatitis B virus (HBV) in newborn infants after fetal HBeAg exposure. This study compared anti-HBs responses to hepatitis B vaccination in infants who were born to HBeAg-positive and -negative mothers respectively, to investigate whether fetal HBeAg exposure may induce immunotolerance to HBV. Totally 265 infants who received recommended neonatal immunoprophylaxis against hepatitis B and had no HBV infection were included. Anti-HBs levels were compared between 124 infants with cord blood positive HBeAg and 141 infants with cord blood negative HBeAg at 7–12 months of age. The infants in two groups had similar age at the follow-up (10.0 ± 2.3 vs 10.1 ± 2.3 months, P = 0.590). Overall, 259 (97.7%) of 265 infants achieved anti-HBs levels (mIU/ml) ≥10 and 6 (2.3%) others had anti-HBs <10. Of 124 HBeAg-positive infants at birth, 46.0%, 39.5%, 12.1%, and 2.4% had anti-HBs levels (mIU/ml) ≥1000, 100–999.9, 10–99.9, and <10, respectively. Of 141 HBeAg-negative infants at birth, 35.5%, 48.9%, 13.5%, and 2.1% showed ≥1000, 100–999.9, 10–99.9, and <10, respectively. The proportions of each anti-HBs level between the two groups were comparable (all P > 0.05). Additionally, the distribution of anti-HBs response levels were also comparable in infants with high and low HBeAg levels (P = 0.818). In conclusions, the fetal HBeAg exposure does not inhibit the antibody response to neonatal hepatitis B vaccination. The data suggest that HBeAg appears not inducing immunotolerance to HBV.

PASylated interferon α efficiently suppresses hepatitis B virus and induces anti-HBs seroconversion in HBV-transgenic mice

Interferon α (IFNα) so far is the only therapeutic option for chronic hepatitis B virus (HBV) infection that can lead to virus clearance. Unfortunately, its application is limited by side effects and response rates are low. The aim of this study was to generate a novel long-acting IFNα with the help of PASylation technology that adds a polypeptide comprising Proline, Alanine and Serine (PAS) to increase plasma half-life. Following evaluation of four selected recombinant murine IFNα (mIFNα) subtypes in cell culture, the most active subtype, mIFNα11, was fused with a 600 amino acid PAS chain. The activity of PAS-mIFNα was assessed by interferon bioassay and further evaluated for induction of interferon-stimulated genes (ISG) and antiviral efficacy in cell culture as well as in HBV-transgenic mice. PAS-mIFNα induced expression of ISG comparable to unmodified mIFNα and, likewise, evoked dose-dependent reduction of HBV replication in vitro. In vivo, PAS-mIFNα led to pronounced suppression of HBV replication without detectable liver damage whereas conventional mIFNα treatment only had a modest antiviral effect. Importantly, all PAS-mIFNα treated mice showed an anti-HBs antibody response, lost HBsAg and achieved seroconversion after three weeks. PASylated IFNα showed a profoundly increased antiviral effect in vivo compared to the non-modified version without toxicity, providing proof-of-concept that an improved IFNα can achieve higher rates of HBV antiviral and immune control.

Response of Preterm Infants of Mothers Who Are Chronic Carriers of Both HBsAg and HBeAg to Pre-52 Containing Hepatitis 8 Vaccine (TGP 943) - A Preliminary Report

This study aimed to examine the immunogenccity and protective efficacy of a pre-S2 containing hepatitis B vaccine (TGP 943, Takada, Japan) in 9 preterrn infants. A control group of preterm infants were given plasma derived hepatitis B vaccine (Korean Green Cross, Korea). All these preterm infants were born to both HBsAG and HBeAg posistive mothers and born in central General Hospital Sanglah Denpasar from January 3, 1992 to October 30, 1992. The gestational ages were 35-37 weeks and birth weights were 2000-2500 grams. The difference of the anti pre-S2 antibody between two groups of preterm infants was evident at month 6. Anti-HBs antibody response was almost same in the two groups of preterm infants. None in preterm infants in this study became positive for HBsAg during follow-up for at least 6 months. 2 of 8 preterm infants in control group become positive for HBsAg during follow up for a t least 6 months. Our study demonstrated a better anti pre-S2 antibody response and also comparable anti-Hbs antibody response in preterms infants vaccinated with a pre-S2 containing hepatitis B vaccine, compared with those with conventional plasma-derived vaccine.

Relative indoleamine 2,3-dioxygenase transcript level concerning anti-HBs titers in response to HBV vaccination in hemodialysis patients

ABSTRACTBackground: Indoleamine 2,3-dioxygenase (IDO) is a negative regulator of the immune system. To approach reasons of variability in the generation of anti-HBs antibodies in response to HBV vaccination among hemodialysis (HD) subjects, we aimed to investigate whether the IDO gene (IDO1) transcript levels are associated with post-vaccination anti-HBs production and IDO1 polymorphic variants.Methods: The IDO1 transcript was determined by qRT-PCR analysis in 110 HD patients. IDO1 (rs3739319, rs9657182) genotyping was carried out by HRM analysis.Results: The relative IDO1 transcript levels were not associated with IDO1 polymorphic variants. There were 16 non-responders (not able to produce anti-HBs >10 IU/L), 74 patients with anti-HBs 10–999 IU/L, and 20 hyperactive responders (anti-HBs ≥1000 IU/L). IDO1 transcript levels were different among these groups (0.832, 0.423–4.373; 1.114, 0.317–6.582; 0.680, 0.164–3.014; respectively, Kruskal-Wallis P = 0.024). Significance in IDO1 transcript was shown between anti-HBs titers 10–999 IU/L and ≥1000 IU/L (P = 0.020). IDO1 transcript level <0.743 indicated 3.38 (1.17–9.72) higher probability of hyperactive immunization (adjusted P = 0.005).Conclusion: In HD patients, ability to generate anti-HBs is not associated with IDO1 transcript levels. Hyperactive anti-HBs responses occur in patients showing lower IDO1 transcript. The latter cannot be predictable by genotyping IDO1 rs3739319 or rs9657182.

Amino acid substitutions Q129N and T131N/M133T in hepatitis B surface antigen (HBsAg) interfere with the immunogenicity of the corresponding HBsAg or viral replication ability

Variants of hepatitis B surface antigen (HBsAg) influenced its antigenicity and immunogenicity. In our study, we aim to investigate biological significance of amino acid (aa) substitutions in HBsAg, Q129 N and T131 N/M133 T, for glycosylation, antigenicity and immunogenicity of variant HBsAg (vtHBsAg) and viral replication. Expression plasmids of vtHBsAg with aa substitutions Q129 L, T123 N, Q129 N and T131 N/M133 T were constructed. Immunofluorescence (IF) staining and Western blot were simultaneously utilized to examine expression of vtHBsAg proteins in Huh7 cells transfected with vtHBsAg constructs. vtHBsAg of Q129 N and T131 N/M133 T created new N-glycosylation and displayed perinuclear distribution by IF staining with the anti-HA. Antigenicity of vtHBsAg of Q129 N and T131 N/M133 T was reduced compared with wild type (wt) HBsAg. In addition, we discovered impaired ability to induce anti-HBs responses against wtHBsAg in mice immunized with plasmids pHBsAg- Q129 N and T131 N/M133 T. Even so, efficient protective response toward wild type HBV can be primed by the two vtHBsAgs in mice. Further, we discovered that vtHBsAg with Q129 N distinctly impaired HBV replication capacity, but vtHBsAg with T131 N/M133 T had no impact on viral replication. Thus, we conclude that vtHBsAg with Q129 N or T131 N/M133 T creates new N-glycosylation and interferes with both the antigenicity and immunogenicity of vtHBsAg. And vtHBsAg with Q129 N impaired HBV replication ability.

Hepatitis B Vaccination in Patients Receiving Oral Antiviral Therapy Without Hepatitis B Immunoglobulin After Liver Transplant

Our study aimed to determine if a double-dose pre-S containing hepatitis B virus (HBV) vaccination (Sci-B-Vac) could elicit an adequate and sustainable immune response in HBV patients who developed spontaneous hepatitis B surface antibody (anti-HBs) response after liver transplant. Patients and MethodsAll patients who received transplants for HBV-related disease for >1 year with normal graft function and hepatitis B surface antigen seronegativity were evaluated. They received a 40-μg HBV vaccine if they were responders in our previous vaccine trial, if anti-HBs was positive for >1 year after liver transplant (LT), or if a peak anti-HBs at any time point after LT was >100 mIU/mL. Primary endpoint was the development of anti-HBs ≥ 10 mIU/mL from previous negative value or a 1-log increase from baseline. ResultsA total of 86 patients were recruited; 5 were responders from a previous trial; 45 patients had detectable anti-HBs >1 year after LT, and 36 patients had an anti-HBs >100 mIU/mL. All (5/5, 100%) previous responders responded to booster vaccination. For the remaining 81 patients, 10 of 81 (12.3%) responded. ConclusionAll previous responders responded to booster vaccination, implying durability and memory of HBV immune response, which is an important prerequisite for definitive host immunity for HBV. In patients who had spontaneous anti-HBs production after LT, a single vaccination can induce response in 12.3% of patients.

Evaluation of Immune Response to Hepatitis B Vaccine in Healthcare Workers at a Tertiary Care Hospital

Purpose: Healthcare workers (HCWs) are at high risk of acquiring hepatitis B virus (HBV) infection through occupational exposure which is preventable through hepatitis B vaccination. In the current study, the response to HBV surface antigen (HBsAg) vaccine was assessed in a selected group of HCWs by testing for antibodies against HBsAg (anti-HBs). Methods: Blood samples were collected in all HCWs, who have received the complete schedule of hepatitis B vaccination and anti-HBs levels, were assessed quantitatively in sera using ELISA. Results: The age range of the study participants was 20–55 years. The mean months after the last dose of vaccination were 60.36. Among the 85 participants, 96.5% (n = 82) have protective immunity to hepatitis B. The anti-Hbs response was similar in both male and female (P > 0.05). There was a decline in immune response as the age was increasing (P < 0.05). The results of the study found a significant decline in the immune response with time (P < 0.05). The anti-Hbs response was declined with smoking habit (P < 0.05) and with increasing body mass index (P < 0.05). Conclusion: Post-HBsAg vaccination immunity to hepatitis B was 96.5% in HCW and was similar to that of global rates. Increasing age, time period, smoking habit, and overweight were associated with decreased immunity. Many studies are needed in developing newer HBV vaccines with very high immunogenicity. Giving highly immunogenic vaccine to HCWs will ensure safety at work by reducing nosocomial transmission which is very much desired in a resource-limited country.

Anti-HBs Antibody Levels and Anti-HBc Detection Among HBV-Vaccinated Freshmen Enrolled in the Department of Laboratory Sciences, Shiraz University of Medical Sciences, Iran

Background: There are few studies indicating the post-neonatal HBV vaccination level of anti-HBs antibody in first-year enrolled university students in Iran. In addition, anti- HBc antibody detection, which is a good indicator of virus exposure, has not been reported in vaccines. Hence, this study was conducted to determine the level of anti-HBs and anti-HBc antibodies in the serum sample of medical laboratory students who had received primary infantile HBV vaccination. Methods: This study was conducted on first-year students enrolled in the department of laboratory sciences at Shiraz University of Medical Sciences, Iran. For determining anti-HBs and anti-HBc titers, 5 mL of venous blood was aseptically collected. Anti-HBs and anti-HBc antibody levels were determined by enzyme-linked immunosorbent assay. HBV DNA was also performed on DNA extracted from individuals positive for an anti-HBc antibody test. Results: Of the 257 vaccinated individuals (188 females and 69 males) who participated in this study, 36.2% showed a non-protective anti-HBs response (anti-HBs < 10 mIU/mL) and 164/257 individuals (63.8%) showed a protective anti-HBs response (anti-HBs ≥ 10 mIU/mL). Significant numbers of females had protective levels of anti-HBS antibody in serum samples in comparison with the males (P < 0.001). Anti-HBc antibody was detected in 3 participants; however, HBsAg was not detected in any of the cases. HBV DNA was found in two. Conclusions: Our results indicate that a substantial number of our study population vaccinated against HBV during childhood showed non-protective anti-HBs antibody level. Therefore, a booster dose of vaccine needs to be scheduled for students with anti-HBs level < 10 mIU/mL prior to the start laboratory internship.

Antibody response to hepatitis B vaccine is independently associated with hepatitis B breakthrough infection among adults: Results from a three-year follow-up study in China

Hepatitis B breakthrough infection (HBBI) and its risk factors are rarely reported among adults in China. In 2009–2010 in three townships of China, hepatitis B vaccine (HepB) administration and anti-HBs detection after HepB were conducted among the residents aged 18–59 years. HBsAg, anti-HBs and anti-HBc were detected for these vaccinees in 2013. A total of 252 out of 4701 vaccinees turned to be positive for anti-HBc in 2013, but nobody was positive for HBsAg. The HBBI rate was 5.36% (95% CI 4.73, 6.04). The highest rate was found in age-group of 18–29 years (7.33%, 95% CI: 5.31, 9.82). The rate was significantly different by the residential townships (P < 0.001) and by the antibody response to HepB (P = 0.003). Multivariate analysis showed that anti-HBs response to HepB was the independent risk factor of HBBI. The study documents the association between hyporesponse to HepB and HBBI among adults. It also suggests more attention should be given to new HBV infection among young adults.

Nasal route favors the induction of CD4+ T cell responses in the liver of HBV-carrier mice immunized with a recombinant hepatitis B surface- and core-based therapeutic vaccine

Immunization routes and number of doses remain largely unexplored in therapeutic vaccination. The aim of the present work is to evaluate their impact on immune responses in naïve and hepatitis B virus (HBV)-carrier mouse models following immunization with a non-adjuvanted recombinant vaccine comprising the hepatitis B surface (HBsAg) and core (HBcAg) antigens. Mice were immunized either by intranasal (i.n.), subcutaneous (s.c.) or simultaneous (i.n. + s.c.) routes. Humoral immunity was detected in all the animal models with the induction of a potent antibody (Ab) response against HBcAg, which was stronger than the anti-HBs response. In the HBV-carrier mouse model, the anti-HBs response was predominantly subtype-specific and preferentially induced by the i.n. route. However, the Ab titers were not sufficient to clear the high concentration of HBsAg present in the sera of these mice. The i.n. route was the most efficacious at inducing cellular immune responses, in particular CD4+ T cells. In naïve mice, cellular responses in spleen were strong and mainly due to CD4+ T cells whereas the CD8+ T-cell response was low. In HBV-carrier mice, high frequencies of HBs-specific CD4+ T cells secreting interferon (IFN)-γ, interleukin (IL)-2 and tumor necrosis factor (TNF)-α were found in liver only after i.n. immunization. Increased frequencies of CD4+ T cells expressing the integrin CD49a in liver suggest a role of nasal route in the cellular homing process. Multiple dose schedules appear to be a prerequisite for protein-based immunization in order to overcome immunotolerance in HBV-carrier mice. These findings provide new avenues for further preclinical and clinical development.

European Recommendations for the Management of Healthcare Workers Occupationally Exposed to Hepatitis

Exposure prevention is the primary strategy to reduce the risk of occupational bloodborne pathogen infections in healthcare workers (HCW). HCWs should be made aware of the medicolegal and clinical relevance of reporting an exposure, and have ready access to expert consultants to receive appropriate counselling, treatment and follow-up. Vaccination against hepatitis B virus (HBV), and demonstration of immunisation before employment are strongly recommended. HCWs with postvaccinal anti-HBs levels, 1-2 months after vaccine completion, .or=10 mIU/mL are considered as responders. Responders are protected against HBV infection: booster doses of vaccine or periodic antibody concentration testing are not recommended. Alternative strategies to overcome non-response should be adopted. Isolated anti-HBc positive HCWs should be tested for anti-HBcIgM and HBV-DNA: if negative, anti-HBs response to vaccination can distinguish between infection (anti-HBs .or=50 mIU/ml 30 days after 1st vaccination: anamnestic response) and false positive results(anti-HBs .or=10 mUI/ml 30 days after 3rd vaccination: primary response); true positive subjects have resistance to re-infection. and do not need vaccination The management of an occupational exposure to HBV differs according to the susceptibility of the exposed HCW and the serostatus of the source. When indicated, post-exposure prophylaxis with HBV vaccine, hepatitis B immunoglobulin or both must be started as soon as possible (within 1-7 days). In the absence of prophylaxis against hepatitis C virus (HCV) infection, follow-up management of HCV exposures depends on whether antiviral treatment during the acute phase is chosen. Test the HCW for HCV-Ab at baseline and after 6 months; up to 12 for HIV-HCV co-infected sources. If treatment is recommended, perform ALT (amino alanine transferase) activity at baseline and monthly for 4 months after exposure, and qualitative HCV-RNA when an increase is detected. Introduction Bloodborne pathogens such as hepatitis B (HBV) and C virus (HCV) represent an important hazard for healthcare workers (HCWs) (1). In the general population, HCV prevalence varies geographically from about 0.5% in northern countries to 2% in Mediterranean countries, with some 5 million chronic carriers estimated in Europe; while HBV prevalence ranges from 0.3% to 3%. The World Health Organization (WHO) estimates that each year in Europe 304 000 HCWs are exposed to at least one percutaneous injury with a sharp object contaminated with HBV, 149 000 are exposed to HCV and 22 000 to HIV. The probability of acquiring a bloodborne infection following an occupational exposure has been estimated to be on average.

Elevated SAP/SLAM expression in hepatitis B vaccine responders, but not in non-responders among chronic hepatitis C patients.

About 5%-10% of vaccinated individuals fail to produce a protective level of anti-hepatitis B surface antibody (anti-HBs) though hepatitis B vaccines show excellent immunogenicity in the general population. The percentage of humoral immunity failure to hepatitis B vaccination is about 30% in individuals infected with hepatitis C virus (HCV). However, mechanisms on the higher non-responsive rate in HCV patients are still unknown. Our study was conducted to describe the potential mechanisms of the Singling Lymphocytic Activation Molecule (SLAM) and SLAM-Associated Protein (SAP) between T cells and B cells borders during humoral immunity response. Based on anti-HBs Ab titers post immunization, we designated three groups: healthy controls (HC), vaccine responders in HCV-infected patients (VR), and vaccine non-responders in HCV-infected patients (VNR), respectively. Protein and mRNA expression levels of SAP and SLAM were determined among three groups at two time points, pre-vaccination and post-vaccination, respectively. For VR and HC, mRNA and protein expression levels of SAP and SLAM were elevated post-vaccination. However, these changes were not seen in VNR. Increased expression levels of SAP and SLAM may be associated with the development of a protective anti-HBs Ab response to hepatitis B vaccination. Therefore, modulation of SAP and SLAM may be considered as a strategy to improve vaccination for HCV-infected patients.

The maternal viral threshold for antiviral prophylaxis of perinatal hepatitis B virus transmission in settings with limited resources: A large prospective cohort study in China.

Antiviral therapy has been documented to reduce perinatal transmission of hepatitis B virus (HBV) in highly viremic mothers. This large prospective cohort study conducted in China aims to delineate the maternal viral threshold for consideration of antiviral prophylaxis in settings with limited resources. A total of 1177 mother-infant pairs with positive maternal hepatitis B surface antigen (HBsAg) under current passive-active prophylaxis regimen were enrolled from community health centers in Jiangsu and Henan provinces, China. Maternal hepatitis B e antigen (HBeAg) status and viral load were tested at 36-40 weeks of gestation. Post-vaccination serologic testing was performed at 7 and 12 months of age. HBeAg-positive mothers (419/1177; 35.6%) had significantly higher viral loads, compared with HBeAg-negative mothers (758/1177; 64.4%) (8.12 vs. 2.69 log IU/mL, p < .0001). Twenty infants, born to HBeAg-positive mothers with high viral loads (median, 8.38; range: 7.82-9.22 log IU/mL), were infected at 7 months of age. In contrast, none of the HBeAg-negative mothers transmitted HBV to their offspring. After adjustment for the other risk factor, a higher maternal viral load was significantly associated with a higher risk of transmission (adjusted odds ratio, 3.78; 95% confidence interval: 1.46-9.81; p = .006). The rates of passive-active immunoprophylaxis failure were 0.0% (0/789), 0.0% (0/27), 0.0% (0/32) and 6.1% (20/329) at maternal viral loads of <5, 5-6, 6-7 and ≥7 log IU/mL, respectively. The antibody to hepatitis B surface antigen (anti-HBs) response rate was 98.4% (1138/1157) at 7 months of age. Results from this study indicate that the maternal viral threshold associated with perinatal transmission of HBV is 7 log IU/mL, which may be appropriate for consideration of antiviral prophylaxis in settings with limited resources.