Immunoprophylaxis failure and vaccine response in infants born to mothers with chronic hepatitis B infection in Djibouti

BACKGROUND In endemic areas,vertical transmission of hepatitis B virus(HBV)remains a major source of the global reservoir of infected people.Eliminating mother-to-child transmission(MTCT)of HBV is at the heart of World Health Organization’s goal of reducing the incidence of HBV in children to less than 0.1%by 2030.Universal screening for hepatitis B during pregnancy and neonatal vaccination are the main preventive measures.AIM To evaluate the efficacy of HBV vaccination combined with one dose of immunoglobulin in children born to hepatitis B surface antigen(HBsAg)-positive mothers in Djibouti city.METHODS We conducted a study in a prospective cohort of HBsAg-positive pregnant women and their infants.The study ran from January 2021 to May 2022,and infants were followed up to 7 mo of age.HBV serological markers and viral load in pregnant women were measured using aVidas microparticle enzyme-linked immunosorbent assay(Biomérieux,Paris,France)and the automated Amplix platform(Biosynex,Strasbourg,France).All infants received hepatitis B immunoglobulin and were vaccinated against HBV at birth.These infants were closely monitored to assess their seroprotective response and for failure of immunoprophylaxis.Simple logistic regression was also used to identify risk factors associated with immunoprophylaxis failure and poor vaccine response.All statistical analyses were performed with version 4.0.1 of the R software.RESULTS Of the 50 pregnant women recruited,the median age was 31 years,ranging from 18 years to 41 years.The MTCT rate in this cohort was 4%(2/50)in HBsAg-positive women and 67%(2/3)in hepatitis B e antigen-positive women with a viral load>200000 IU/mL.Of the 48 infants who did not fail immunoprophylaxis,8(16%)became poor responders(anti-HB<100 mIU/mL)after HBV vaccination and hepatitis B immunoglobulin,while 40(84%)infants achieved a good level of seroprotection(anti-HB>100 mIU/mL).Factors associated with this failure of immunoprophylaxis were maternal HBV DNA levels(>200000 IU/mL)and hepatitis B e antigen-positive status(odds ratio=158,95%confidence interval:5.05-4958,P<0.01).Birth weight<2500 g was associated with a poor immune response to vaccination(odds ratio=34,95%confidence interval:3.01-383.86,P<0.01).CONCLUSION Despite a failure rate of immunoprophylaxis higher than the World Health Organization target,this study showed that the combination of immunoglobulin and HBV vaccine was effective in preventing MTCT of HBV.Therefore,further studies are needed to better understand the challenges associated with immunoprophylaxis failure in infants in Djibouti city.

Prevalence of Children Vaccinated against Viral Hepatitis B in Brazzaville

Introduction: Viral hepatitis B (VHL) is a public health problem, particularly in sub-Sahara Africa. The aim of this study was to assess vaccination coverage against HBV in children in Brazzaville. Patients and Methods: This was a cross-sectional analytical study conducted in Brazzaville health centres from January to September 2019. It involved children aged between six months and six years who received a vaccination against HBV. Sampling was exhaustive and based on stratified sampling. Results: The overall prevalence of children vaccinated against HBV in Brazzaville was 96.2%. It was insufficient in the Talangai health district (79%). The pentavalent vaccine was administered to 97.7% of children, 85% of whom had received all three doses. The reasons for incomplete vaccination were parents’ ignorance of HVB (85.6%) and of vaccination (14.3%). Conclusion: Although the prevalence of vaccinated children is high in Brazzaville, it is still insufficient in some health districts, particularly Talangai, because parents are unaware of the disease and of vaccination. Pentavalent is the only vaccine available in the national vaccination programme, which is why an effective national vaccination policy needs to be put in place. .

Perception of Medical Students towards Hepatitis B Virus Infection and Hepatitis B Vaccination in a Private Tertiary Hospital in Jos North Local Government, Plateau State, Nigeria

Background: Prevention is one of the safe schemes against the high prevalence of viral Hepatitis. Negative perceptions or perceptions about the risks of hepatitis B among medical students and health care workers may influence the behavioral pattern and adoption of preventive measures against the virus and can affect the uptake of the Hepatitis B vaccine. This study assesses the perception of medical students towards Hepatitis B virus infection and Hepatitis B Vaccination in a Private Tertiary Hospital in Jos North Local Government, Plateau State, Nigeria. Methods: This was a descriptive cross-sectional study done in August 2021 among 236 clinical medical students using a multistage sampling technique. Data was collected using an interviewer-administered structured questionnaire and analysed using the IBM SPSS 28 (Statistical Package for the Social Sciences). Ethical approval was granted by Bingham University Teaching Hospital, Ethics Committee, Jos, Plateau State. Results: Two-thirds of respondents were of the opinion that they are at risk of contracting HBV. Half were of the opinion that the risk is very much while a third believed the risk is moderate. Among those who think they are not at risk of contracting HBV, the majority felt so because they are vaccinated while 10.3% believe that they are safe. 43.2% of respondents think that HBV Vaccine is very effective in preventing HBV infection while 39.8% think it is slightly effective, and 7.6% think it is not effective. Almost all respondents, 99.2% are of the opinion that HBV Vaccination is important for students while 0.8% think it is not important. The majority of the respondents at 95.8% were willing to be screened for HBV. The majority (85.6%) of respondents are willing to pay for HBV Vaccine as against 14.4% of respondents who are not willing to pay. Conclusion: Summarily, 21 (8.9%) of the students had a negative perception of Hepatitis B Vaccination, and 215 (91.1%) had a positive perception of Hepatitis B Vaccination. Perception-sustaining events like seminars, workshops, road shows, and campaigns should be organized among students and health workers.

Hepatitis B Vaccination Coverage among University Students in Sub-Saharan Africa: Systematic Review and Meta Analysis

Introduction: Hepatitis B is an infectious disease that remains a real public health problem in Africa. Students represent a group at risk for this disease. The objective of this study was to estimate the hepatitis B vaccination coverage rate among students in sub-Saharan Africa. Methods: A systematic search of databases (PubMed, AJOL) and a manual search of Google Scholar was conducted to retrieve all published studies reporting hepatitis B vaccination coverage among students in sub-Saharan Africa. The pooled coverage rate was estimated with a 95% confidence interval (CI) in a random-effects meta-analysis. Results: A total of 35 studies were included and included 20,520 students. The mean age was 22.1 ± 5.1 years with a predominance of female sex (sex ratio F/M = 1.05). The vaccination coverage rate was 28.8% [95% CI: 22.9% - 34.7%]. Disaggregation allowed to estimate coverage rates of 29.8% [95% CI: 22.9% - 36.7%], 23.4% [95% CI: 9.4% - 37.4%] and 17.0% [95% CI: 14.4% - 19.5%] respectively in West Africa, East Africa and Central Africa. Conclusion: Less than a third of students in sub-Saharan Africa are protected against hepatitis B. However, the majority of this target group is at risk of infection. It would be relevant to screen and, if necessary, vaccinate all new students.

Review of Albanian studies suggests the need for further efforts to counteract significant hepatitis B virus prevalence

BACKGROUND Hepatitis B virus(HBV)is categorized as one of the smallest enveloped DNA viruses and is the prototypical virus of the Hepatoviridae family.It is usually transmitted through body fluids such as blood,semen,and vaginal secretions.The majority(more than 95%)of immunocompetent adults infected with HBV spontaneously clear the infection.In the context of the high prevalence of HBV infection in Albania,the research gap is characterized by the lack of studies aimed at advancing the current understanding and improving the prevailing situation.The main objective of this study was to address the low rate of HBV diagnosis and the lack of a comprehensive national program to facilitate widespread diagnosis.AIM To analyze the prevalence of HBV infection in Albania and elucidate the persistently high prevalence despite efforts and measures implemented.METHODS Using a systematic literature review,we collected existing research on the epidemiology of HBV in Albania from PubMed,Cochrane Library,Google Scholar,and Albanian Medical Journals,focusing on studies published after the 1980s and conducted solely in the Albanian population.RESULTS The findings reveal a dynamic shift in HBV prevalence in Albania over several decades.Initially high,the prevalence gradually declined following the implementation of screening and vaccination programs.However,the prevalence rates have remained notably high,exceeding 8%in recent years.Contributing factors include vertical transmission,inadequate healthcare infrastructure,and challenges in screening and diagnosis.Studies among Albanian refugees in neighboring countries also reported high prevalence rates,emphasizing the need for transnational interventions.Despite advancements in screening,vaccination,and healthcare infrastructure,Albania continues to face a substantial burden of HBV infection.CONCLUSION The persistence of high prevalence underscores the complexity of the issue,requiring ongoing efforts to ensure a comprehensive understanding and effective mitigation.Addressing gaps in vaccination coverage,improving access to screening and diagnosis,and enhancing public awareness are crucial steps toward reducing HBV prevalence in Albania.

Hepatitis B Vaccination in Medical and Dental Students: A Cross-Sectional Study

Background: Medical and dental students are at risk of Hepatitis B Virus (HBV) infection. The study aimed to assess the vaccination status against Hepatitis B Virus of students in clinical and non-clinical years of a private medical and dental college, and their knowledge, attitude, and awareness about the subject. Methods: A cross-sectional study was conducted using a pretested, self-administered questionnaire among 203 medical and dental students of CMH Lahore Medical College and Institute of Dentistry (CMH LMC & IOD) in Lahore, Pakistan. Participants were evaluated for their knowledge and vaccination status against Hepatitis B Virus. Students were considered to be fully vaccinated (recipients of 3 doses), partially vaccinated (recipients of 1 or 2 doses), and unvaccinated. Comparisons were made between students of clinical and non-clinical years. Data was entered and analysed using Statistical Package for the Social Sciences (SPSS) version 23. Results: Only 66% (n = 134) of the 203 participants had ever received a Hepatitis B Virus vaccine out of which a meagre 17.2% (n = 35) were fully vaccinated. No significant difference was found in vaccine uptake between students of clinical and non-clinical years (p-value = 0.181) despite significant differences seen in the knowledge of vaccination schedule (p-value = 0.001), the prevalence of needle-stick injuries (p-value = 0.001), and knowledge of protocols to be followed after a needle-stick injury (p-value = 0.001). Conclusion: Our study found that a large proportion of the student population is vulnerable to HBV infection. There is a need to create awareness regarding the subject to increase vaccine uptake. HBV vaccination should be offered to all currently enrolled students and be made mandatory at the time of admission in the future.

肝移植术后乙肝主动免疫重建受者停用HBIG和(或)核苷(酸)类似物的长期安全性和有效性

目的探讨乙型病毒性肝炎(乙肝)相关疾病肝移植受者接种乙肝疫苗成功后长期停用乙型肝炎免疫球蛋白(HBIG)和(或)核苷(酸)类似物(NAs)预防乙型肝炎病毒(HBV)再感染的安全性及有效性。方法回顾性分析76例接种乙肝疫苗后成功重建乙肝主动免疫的肝移植受者的基本资料,分析疫苗接种及应答情况、应答者停用HBIG和(或)NAs的随访结果、停用HBIG和(或)NAs后HBV再感染情况。结果肝移植术后至开始接种乙肝疫苗的时间间隔为26(20,40)个月。接种疫苗至应答时间为15(8,27)个月。初始76例受者全部停用HBIG,36例受者停用HBIG和NAs。随访期间,76例停用HBIG受者中12例恢复使用HBIG,36例停用HBIG和NAs者中16例恢复使用NAs。HBIG和NAs停用时间分别为135(98,150)个月与133(34,149)个月。16例应答者未接种过加强针,36例应答者定期接种加强针,第1次接种加强针的时间距离停用HBIG的间隔时间为44(11,87)个月,未接种加强针和接种加强针的应答者一般资料比较差异均无统计学意义(均为P>0.05)。截至随访日,9例受者失访,5例HBV再感染,3例受者死亡,1例受者移植物丢失并进行二次肝移植。5例HBV再感染受者中4例发生病毒变异。再感染者与未感染者是否停用过NAs、移植前乙型肝炎e抗原(HBeAg)是否为阳性差异有统计学意义(均为P<0.05)。结论乙肝相关疾病肝移植术后乙肝主动免疫重建成功的受者长期停用HBIG是可行和安全的,但能否同时停用NAs还需要进一步研究。

A 12-year cohort study on the efficacy of plasmaderived hepatitis B vaccine in rural newborns

AIM To understand the anti-HBs persistenceand the long-term preventive efficacy in ruralnewborns after vaccination with plasma-derivedhepatitis B vaccine.METHODS In the time of expanded program onimmunization(EPI),the newborns werevaccinated with 10μg×3 doses of hepatitis Bvaccine and 762 newborns who were HBsAgnegative after primary immunization wereselected for cohort observation from 1986 to1998.Their serum samples were detectedqualitatively and quantitatively for hepatitis Binfecting markers,including HBsAg,anti-HBsand anti-HBc by SPRIA Kits.The annual HBsAgpositive conversion rate was counted by life-table method.RESULTS①The anti-HBs positive rate was94.44% for the babies born to HBsAg negativemothers and 84.21% for those born to HBsAgpositive mothers in the 1st year afterimmunization,and dropped to 51.31% and52.50% in the 12th year respectively.GMT valuewas dropped from 31.62 to 3.13 and 23.99 to 3.65in the 2nd to the 12th year respectively.Therewas a marked drop in GMT at the 3rd to the 5thyear,and in anti-HBs positive rate at the 9th tothe 10th year.②In the period of 12 yearsobservation,the person-year HBsAg positive conversion rates were 0.12%(5/4150.0)innewborns born to HBsAg negative mothers and0.20%(1/508.0)in those born to HBsAgpositive mothers,and none of the HBsAgpositive converted children became HBsAgchronic carriers.Compared with the baselinebefore immunization,the protective rates were97.19% and 95.32% respectively.CONCLUSION The protective efficacy ofplasma-derived hepatitis B vaccine persisted atleast 12 years,and a booster dose seems notnecessary within at least 12 years after theprimary three-doses immunization to newbornsborn to HBsAg negative mothers.

Long term effectiveness of infancy low-dose hepatitis B vaccine immunization in Zhuang minority area in China

AIM To observe the long-term effectiveness of low-dose immunization strategy and risk factors of HBsAg carriers in immunized children of Zhuang minorities of Longan County in the 9th year after infancy immunization.METHODS Two epidemiologic methods, a cross-sectional follow-up study and a case-control study, were used for the evaluation of the serological effect and the determination of the risk factors. Hepatitis B virus markers were detected with radioimmunoassay.RESULTS The protective anti-HBs-positive rate was 43.8% in 1183 children aged 1-9 years, who were immunized with three doses of 10 μg hepatitis B vaccine in infancy according to 0, 1 and 6 months schedule. It declined from 87.9% in the first year to 37.1% in the 9th year after vaccination. The HBsAg-positive rate was 1.6%, not increasing with age during 9 years after the infant immunization program. Compared with 14.0% of HBsAg-positive rate of the baseline survey in 1985, the effectiveness of hepatitis B vaccine immunization was 88.6%. Of 36 immunized children with positive HBsAg, 89.1% were likely attributable to HBsAg positivity of their mothers.CONCLUSION The long-term effectiveness of infancy low-dose hepatitis B vaccine immunization is high, and the booster is not needed 9 years after the vaccination in the Zhuang minority area where hepatitis B is highly endemic. A high-dose immunization strategy should be recommended in order to further decrease the current HBsAg-positive rate.

Persistence of hepatitis B vaccine immune protection and response to hepatitis B booster immunization

ＡｂｓｔｒａｃｔＡＩＭＴｏｉｄｅｎｔｉｆｙｔｈｅｐｅｒｓｉｓｔｅｎｃｅｏｆｉｍｍｕｎｅｐｒｏｔｅｃｔｉｏｎｏｆＣｈｉｎａｍａｄｅ，ｐｌａｓｍａｄｅｒｉｖｅｄｈｅｐａｔｉｔｉｓＢｖａｃｃｉｎｅａｆｔｅｒｉｎｆａｎｃｙｉｍｍｕｎｉｚａｔｉｏｎａｎｄｔ...

Humoral and cellular immunogenecity of DNA vaccine based on hepatitis B core gene in rhesus monkeys

INTRODUCTIONHepatitis B virus (HBV) is the most commonetiologic agent for infectious liver diseases. It isestimated that there are more than 250 millionchronic HBV carriersin the world today and thereis a significant association among persistentinfection, liver cirrhosis and hepatocellularcarcinoma[1-3].

Long term efficacy of plasma derived hepatitis B vaccine among Chinese children: a 12 year follow up study

ＩＮＴＲＯＤＵＣＴＩＯＮＴｏｅｖａｌｕａｔｅｌｏｎｇｔｅｒｍｅｆｉｃａｃｙｏｆａｐｌａｓｍａｄｅｒｉｖｅｄｈｅｐａｔｉｔｉｓＢｖａｃｃｉｎｅａｎｄｐｒｏｖｉｄｅｅｖｉｄｅｎｃｅｆｏｒｄｅｃｉｓｉｏｎｍａｋｉｎｇｏｎｔｈｅｖａｃｃｉｎｅｂｏｏｓｔ...

Hepatitis B vaccine by intradermal route in non responder patients:An update

Vaccination is the main prophylactic measure to reduce the mortality caused by hepatitis B virus (HBV) infection in healthy subjects since the immune response to hepatitis B recombinant vaccination occurs in over 90% of general population. Individuals who develop an anti-HBs titer less than 10 mIU/mL after primary vaccination cycle are defined &#x0201c;no responders&#x0201d;. Many factors could cause a non response to the HBV vaccination, such as administration of the vaccine in buttocks, impaired vaccine storage conditions, drug abuse, smoking, infections and obesity. Moreover there are some diseases, like chronic kidney disease, human immunodeficiency virus infection, chronic liver disease, celiac disease, thalassaemia, type&#x02005;I&#x02005;diabetes mellitus, down&#x02019;s syndrome and other forms of mental retardation that are characterized by a poorer response to HBV vaccination than healthy subjects. To date it is still unclear how to treat this group of patients at high risk of hepatitis B infection. Recent studies seem to indicate that the administration of HBV recombinant vaccine by the intradermal route is very effective and could represent a more useful strategy than intramuscular route. This review focuses on the use of anti hepatitis B vaccine by intradermal route as alternative to conventional intramuscular vaccine in all non responder patients. A comprehensive review of the literature using PubMed database, with appropriate terms, was undertaken for articles in English published since 1983. The literature search was undertaken in September 2013.

Recent advances in vaccination of non-responders to standard dose hepatitis B virus vaccine

Hepatitis B virus(HBV) infection is a global health problem. It is estimated there are more than 2 billion individuals exposed to the virus and 250 million are chronically infected. Hepatitis B is the cause of more than 600000 annual deaths due to cirrhosis and hepatocellular carcinoma. An effective vaccine exists and preventative initiatives center around universal vaccination especially in those at highest risk. Effective vaccination algorithms have led to a significant decline in the development of new infections and its devastating consequences. The vaccine is administered intramuscularly in three doses, with 95% showing long lasting serologic immunity. An additional fourth dose or a repeated higher dose three course regimen is given to those that fail to show immunity. Despite these additional regimens, some remain vulnerable to hepatitis B and are deemed nonresponders. Individuals with chronic disease states such as kidney disease, liver disease, diabetes mellitus, as well as those with a genetic predisposition, and those on immunomodulation therapy, have the highest likelihood of non-response. Various strategies have been developed to elicit an immune response in these individuals. These include increased vaccination dose, intradermal administration, alternative adjuvants, alternative routes of administration, co-administration with other vaccines, and other novel therapies. These alternative strategies can show improved response and lasting immunity. In summary, HBV vaccination is a major advance of modern medicine and all individuals at risk should be sought and vaccinated with subsequent adequate titers demonstrated.

Relationship between T-lymphocyte cytokine levels and sero-response to hepatitis B vaccines

AIM: To investigate the cellular defects by analyzing the (Th1/Th2) cytokine levels in vaccine responders and non-responders. METHODS: Peripheral blood mononuclear cell (PBMC) from responders and non-responders were stimulated with or with out recombinant HBsAg or PHA. Broad spectrum of cytokines viz (Th1) IFN-γ, IL-2, TNF-α, IL-12 and (Th2) IL-10, IL-4 were measured after in vitro stimulation with recombinant HBsAg and were compared with respective antibody titers. RESULTS: A significant decrease (P = 0.001) in Th1 and Th2 cytokines namely, IL-2, INF-γ, TNF-α and IL-10in non-responders was observed. The level of IL-4 was not significant between the three groups. Furthermore, despite a strong Th1 and Th2 cytokine response, the level of IL-12 was elevated in high-responders compared to other groups (P = 0.001) and demonstrated a positive correlation with anti-HBs titers and Th1 cytokine response. CONCLUSION: Our findings suggest that unrespon-siveness to recombinant hepatitis B vaccines (rHB) is multifactorial, including specific failure of antigen presentation or the lack of both T helper Th1 and Th2 response.

Immunogenicity and reactogenicity of a recombinant hepatitis B vaccine in subjects over age of forty years and response of a booster dose among nonresponders

AIM:The study was initiated to evaluate the reactogenicity and immunogenicity of a recombinant hepatitis B vaccine in age group >40 years and to study the response of a single booster dose in primary non-responders to the hepatitis B vaccination. METHODS:A total of 102 volunteers without markers of hepatitis B infection (negative for HBsAg,anti-HBc antibody, HBeAg and anti-HBs antibody) received 20μg of recombinant HB vaccine intramuscularly at 0,1,and 6 months.Anti HBs titers were evaluated by a quantitative Elisa kit at 90 and 210 days.A booster dose of 20μg HB vaccine was given after 6 months of the 3^(rd) vaccine dose to the 15 non- responders and anti-HBs titers were measured after i month. RESULTS:Seroprotection (anti-HBs GMT^3 10 IU/L) was achieved in 85.3 % (87/102) volunteers.The mean GMT titers of the vaccine responders was 136.1 IU/L.Of the seroprotected individuals,there were 32.4% (33/102) hyporesponders (anti- HBs titers <10-99 mIU/ml) and 52.9% (54/102) were responders (anti-HBs titers >100 IU/L).All the non-responders (15/15) responded to a single dose of the booster dose of recombinant HB vaccine and their mean anti-HBs antibody titers were more than 100.5 mIU/ml after the booster dose. CONCLUSION:Recombinant hepatitis B vaccine offers good seroprotection in the age group >40 years and has a good safety profile.A single booster dose after 6 months in primary non-responders leads to good seroprotective anti-HBs antibody titers.However,larger population based studies are needed to evaluate the role of a booster dose in selected group of non-responders and whether such an approach will be cost effective.

Immune response to an indigenously developed r-Hepatitis B vaccine in mixed population: Study of an accelerated vaccination schedule

AIM: To establish the safety and efficacy of an indigenously developed r-hepatitis B vaccine using an accelerated schedule and to highlight the social awareness and commitment in preventing the spreading of hepatitis B virus infection. METHODS: The study was a multicentric, double blind, randomized (3:1) study using three doses of vaccine immunization schedule (20μg for those above 10 years old and 10 μg for those below 10 years old) on d 0, 30 and 60. One hundred and sixty-six subjects were enrolled (87 males and 76 females aged 5-35 years). The main outcome measure was assessment of immunogenicity and safety. RESULTS: A 100% seroconversion response was observed on the 30th d after the 1st injection in both the experimental groups. The sero-protection data reported a 41.2-65.6% response on the 30th d after the 1st injection and reached 100% on the 60th d. Descriptive statistical analysis showed a geometric mean titer value of 13.77 mIU/mL in the test (BEVAC) group and 10.95 mlU/mL in the commercial control (ENGERIX-B) group on the 30th d after the 1st injection. The response on the 60th d showed a geometric mean titre value (GMT) of 519.84 mlU/mL in the BEVAC group and 475.46 mlU/mL in the ENGERIX-B group. On the 90th d, the antibody titer response was observed to be 2627.58 mlU/mL in the BEVAC group and 2272.72 mlU/mL in the ENGERIX-B group. Two subjects in each group experienced pains at injection site after the first vaccination. A total of six subjects in both groups experienced a solicited adverse reaction, which included pains, swelling and redness at the injection site, three subjects in the group-B had a pain at the injection site after the third dose. No other serious adverse events occurred and no dose-related local or general symptoms were observed during the study. CONCLUSION: The vaccine is safe, efficacious and immunogenic in comparison with the well documented ENGERIX-B.

Immune response to hepatitis B virus vaccine in celiac subjects at diagnosis

AIM To evaluate hepatitis B virus(HBV) vaccine response and correlation with human leukocyte antigens(HLA) and/or gluten intake in celiac patients at diagnosis.METHODS Fifty-one patients affected by celiac disease, diagnosed at the Department of Pediatrics of the University of Catania(Italy), were recruited. All patients were tested at admission for immunization against HBV, according to findings from analysis of quantitative HBV surface antibody(anti-HBs). The anti-HBs titer was measured by enzyme-linked immunosorbent assay. Following the international standards, subjects with antibody titer < 10 IU/L were defined as non-responders. The prevalence of responders and non-responders among celiac subjects and the distribution of immunization for age were examined. In addition, the prevalence of responders and non-responders was assessed for correlation to HLA and clinical features at diagnosis of celiac disease.RESULTS The entire study population was divided into three groups according to age: 24 patients aged between 0to 5.5 years(48.9%, group A); 16 aged between 5.5 and 9.5 years(30.61%, group B); 9 aged between 9.5 and 17 years(18.75%, group C). Comparison of the percentage of responders and non-responders between the youngest and the oldest age group showed no significant difference between the two groups(P > 0.05). With regard to the HLA haplotype, comparison of the distribution of vaccination response showed no statistically significant difference between the different genotypes(homozygosity for the HLADQ2 haplotype compared with HLADQ2/DQ8 heterozygosity or other haplotypes; P > 0.05). Moreover, distribution of the responders according to clinical features of celiac disease showed no statistically significant differences(P > 0.05).CONCLUSION This prospective study confirmed the lower percentage of response to HBV vaccine in celiac subjects. However, the underlying mechanism remains unclear and further studies are needed.

Hepatitis B vaccine in celiac disease:Yesterday,today and tomorrow

Some studies showed that in celiac patients the immunological response to vaccination is similar to that one found in general population except for vaccine against hepatitis B virus (HBV).The non-responsiveness to HBV vaccine has also been described in healthy people,nevertheless the number of non-responders has been demonstrated to be higher in celiac disease (CD) patients than in healthy controls.Several hypothesis explaining this higher rate of unresponsiveness to HBV vaccine in CD patients have been described,such as the genetic hypothesis,according with CD patients carrying the disease-specific haplotype HLA-B8,DR3,and DQ2,show a lower response to HBV vaccine both in clinical expressed CD patients and in healthy people carrying the same haplotype.On the other hand,it has been demonstrated that the gluten intake during the vaccination seems to influence the response to the same vaccine.Moreover,it has been demonstrated a possible genetic predisposition to hepatitis B vaccine nonresponsiveness likely due to the presence of specific human leukocyte antigen haplotypes and specific single nucleotide polymorphism in genes of cytokine/cytokinereceptors and toll like receptors,but the pathogenic mechanism responsible for this low responsiveness still remains unclear.The aim of this review is to focus on the possible pathogenic causes of unresponsiveness to HBV vaccine in CD patients and to propose an alternative vaccination schedule in order to improve the responsiveness to HBV vaccine in this at-risk patients.

HBsAg, HBcAg, and combined HBsAg/HBcAg-based therapeutic vaccines in treating chronic hepatitis B virus infection

BACKGROUND: As the host immunity is diminished in patients with chronic hepatitis B (CHB), different approaches have been used to up-regulate their immune responses to produce therapeutic effects. But, cytokines, growth factors and polyclonal immune modulators could not exhibit sufficient therapeutic effects in these patients. Immune therapy with HBV-related antigens (vaccine therapy) has been used in CHB patients. But there is a paucity of information about the design of HBV antigen-based immune therapy in these patients. DATA SOURCE: Preclinical and clinical studies on immune therapy with HBsAg-based vaccine, HBcAg and combination of HBsAg/HBcAg-based vaccines have been discussed. RESULTS: HBsAg-based prophylactic vaccine was used as an immune therapeutic agent in CHB patients; however, monotherapy with HBsAg-based immune therapy could not lead to sustained control of HBV replication and/or liver damages. HBsAg-based vaccine was used as a combination therapy with cytokines, growth factors, and antiviral drugs. HBsAg-based vaccine was also used for cell-based therapy. However, satisfactory therapeutic effects of HBsAg-based vaccine could not be documented in CHB patients. In the mean time, evidences have supported that HBcAg-specific immunity is endowed with antiviral and liver protecting capacities in CHB patients. Recent data concentrate on the clinical use of combined HBsAg- and HBcAg-based vaccines in CHB patients.CONCLUSION: Antigen-based immune therapy with HBV- related antigens may be an alternative method for the treatment of CHB patients but proper designs of antigens, types of adjuvants, dose of vaccinations, and routes of administration need further analyses for the development of an effective regimen of immune therapy against HBV.