Hepatitis A.

Hepatitis A is a common viral infection worldwide that is transmitted via the fecal-oral route. The incidence of infection in the United States decreased by more than 90% after an effective vaccine was introduced, but the number of cases has been increasing because of large community outbreaks in unimmunized individuals. Classic symptoms include fever, malaise, dark urine, and jaundice and are more common in older children and adults. People are most infectious 14 days before and seven days after the development of jaundice. Diagnosis of acute infection requires the use of serologic testing for immunoglobulin M anti-hepatitis A antibodies. The disease is usually self-limited, supportive care is often sufficient for treatment, and chronic infection or chronic liver disease does not occur. Routine hepatitis A immunization is recommended in children 12 to 23 months of age. Immunization is also recommended for individuals at high risk of contracting the infection, such as persons who use illegal drugs, those who travel to areas endemic for hepatitis A, incarcerated populations, and persons at high risk of complications from hepatitis A, such as those with chronic liver disease or HIV infection. The vaccine is usually recommended for pre- and postexposure prophylaxis, but immune globulin can be used in patients who are too young to be vaccinated or if the vaccine is contraindicated.

Hepatitis A vaccine immunogenicity 25 years after vaccination in Alaska.

The hepatitis A vaccine is recommended for all children greater than or equal to 1 year of age, however, the duration of vaccine protection is unknown and protection through adulthood is crucial to prevent symptomatic hepatitis later in life. We report on 25 years of follow-up of a cohort of Alaska Native individuals who were vaccinated in early childhood. We assessed the duration of vaccine protection by calculating the geometric mean concentration and proportion of participants with protective levels of IgG antibody to hepatitis A virus (anti-HAV) (≥20 mIU/mL) every 2 to 3 years. We estimated the amount of time until the anti-HAV dropped below protective levels using survival analyses. At 25 years, 43 of the original 144 participants were available, mean anti-HAV levels were 91.5 mIU/mL, and 35 (81.4%) had protective levels of anti-HAV. Using data from all persons and all time points, a survival analysis estimated 78.7% of participants had protective levels of anti-HAV at 25 years. The high level of protective antibodies in this cohort indicate that supplemental doses of hepatitis A vaccine are not needed 25 years after completion of the vaccine series.

Low immune response rate of HIV-infected patients to a single injection of hepatitis A vaccine.

OBJECTIVES: We aimed to evaluate the immune response of HIV-1 positive patients to a single injection of HAV vaccine in a context of vaccine shortage during the 2017 European outbreak. METHODS: We retrospectively enrolled all HIV-1 positive patients vaccinated by a single injection of HAV vaccine Vaqta 50®. HAV serology was performed before and>30 days after the vaccine injection. RESULTS: Among the 73 patients, HIV-1 viral load was≤50 copies/mL in 93.2% of the cases. Medians of CD4 and median ratio of T CD4/CD8 cells were 658/mm3 and 0.9, respectively. A low immune response rate (59.7%) was observed among the patients. Responders had a significantly higher CD4/CD8 cell ratio than non-responders. CONCLUSIONS: A serologic control should be recommended in this population in the event of a single injection vaccination schedule. During routine follow-up, and prior to any untoward event, physicians should assess the vaccination coverage of HIV-infected patients.

Hepatitis A and B Vaccination in the United States.

Use of hepatitis A vaccine is a main component of travel vaccination practices. In the United States, fluctuations in the number of annual hepatitis A infections have occurred recently due to large outbreaks related to imported foods and urban transmission among homeless individuals, warranting consideration for wider local use of hepatitis A vaccine. Hepatitis B vaccine is indicated for all adults, and especially healthcare workers. Since 1992, it has been administered at birth. A new novel hepatitis B vaccine given in two doses one month apart is available and has increased efficacy in adults. This article reviews the complete administration of these hepatitis vaccines.

Short-term immunogenicity and safety of hepatitis-A and varicella vaccines in HIV-exposed uninfected and HIV-unexposed South African children.

BACKGROUND: HIV-exposed uninfected (HEU) children have increased risk of infectious morbidity during early childhood. We evaluated the short-term immunogenicity and safety of single dose inactivated hepatitis-A virus (HAV) vaccine and live attenuated varicella zoster virus (VZV) vaccine in South African children. METHODS: 195 HIV-unexposed and 64 HEU children received either one dose of HAV or VZV vaccine at 18 months of age. Blood samples were tested for hepatitis-A or VZV antibodies before and one month after vaccination by chemiluminescent microparticle immunoassay and enzyme-linked immunosorbent assay, respectively. All children were evaluated for solicited adverse events (AEs). RESULTS: One-month post-vaccination, a similar percentage of HIV-unexposed (91.8%) and HEU (82.9%) children were seropositive for hepatitis-A (p = 0.144). VZV antibody geometric mean fold-rise was also similar in HIV-unexposed (5.6; 95%CI: 4.6-6.7) and HEU children (5.1; 95%CI: 3.7-7.2); however, only 44% HIV-unexposed and HEU seroconverted (titers > 50 mIU/ml). AEs occurred with similar frequency and severity between groups, except for more systemic AEs after VZV vaccination in HEU than HIV-unexposed children. CONCLUSIONS: Single dose HAV and VZV vaccine was similarly immunogenic in HIV-unexposed and HEU children. We did not identify differences in short-term humoral immunity after administration of either a live attenuated or inactivated vaccine. Seroconversion rates after a single dose of VZV vaccine were, however, lower compared to reports from previous studies (85-89%). CLINICAL TRIALS REGISTRATION: NCT03330171.

Alginate-coated chitosan nanoparticles act as effective adjuvant for hepatitis A vaccine in mice.

The numerous recent hepatitis A outbreaks emphasize the need for vaccination; despite the effectiveness of the current ones, developments are needed to overcome its high cost plus some immune response limitations. Our study aims to evaluate the use of chitosan and alginate-coated chitosan nanoparticles as an adjuvant/carrier for the hepatitis A vaccine (HAV) against the traditional adjuvant alum. Immune responses towards (HAV-Al) with alum, (HAV-Ch) with chitosan, and (HAV-aCNP) with alginate-coated chitosan nanoparticles, were assessed in mice. HAV-aCNP significantly improved the immunogenicity by increasing the seroconversion rate (100%), the hepatitis A antibodies level, and the splenocytes proliferation. Thus, the HAV-aCNP adjuvant was superior to other classes in IFN-γ and IL-10 development. Meanwhile, the solution formula of HAV with chitosan showed comparable humoral and cellular immune responses to alum-adjuvanted suspension with a balanced Th1/Th2 immune pathway. The current study showed the potential of alginate-coated chitosan nanoparticles as an effective carrier for HAV. Consequently, this would impact the cost of HAV production positively.

Poor response to hepatitis A vaccination in hematopoietic stem cell transplant recipients.

BACKGROUND: Hepatitis A virus (HAV) infection is highly prevalent in developing countries. In countries experiencing a shift from intermediate/high endemicity to low endemicity, the World Health Organization recommends the incorporation of HAV vaccine into the national vaccination calendar for children aged ≥1 year. Since HAV antibodies wane over time, most HSCT revaccination guidelines advise vaccination as optional, following the country recommendation. However, no study has evaluated the serological response to HAV vaccine in allogeneic HSCT recipients. METHODS: We conducted a prospective study in 46 HSCT recipients who received two doses of inactivated HAV vaccine. Blood samples were taken before vaccination to determine HAV prevalence rates, and before and 4-6 weeks after the second dose. Specific anti-HAV antibodies were detected by a competitive commercial enzyme immune assay. RESULTS: Patients received the first dose of vaccine at a median of 332.5 (120-4134) days after HSCT. Median absolute lymphocyte count at vaccination was 1947 (696-12 500)/mm3 . The seroprevalence rate was 93.5% at inclusion. Although safe and well tolerated, the serological response to HAV vaccine in susceptible patients was poor (33%), and no boost effect was observed in seropositive patients. CONCLUSIONS: In areas with intermediate/high seroprevalence of HAV, serology should be recommended prior to referral to vaccination. The mechanisms of antibody interference and how to overcome T-cell function deficiency need to be better understood in transplant populations receiving HAV vaccine. Alternative schedules of HAV vaccination should be evaluated in prospective trials.

Statistical modeling alongside observational data predicts long-term immunogenicity of one dose and two doses of pediatric hepatitis A vaccine in the Mendoza province of Argentina.

BACKGROUND: Follow-up for anti-hepatitis A (HA) antibody persistence up to 10 years was conducted after implementation of universal vaccination against HA virus (HAV) in Mendoza, Argentina. Based on these data, statistical modeling was used to predict the antibody persistence to 30 years. METHODS: A non-interventional study evaluated long-term immunogenicity (geometric mean concentrations [GMCs] and seroprotection rate) following routine vaccination with 1 dose (Group 1: N = 436) or 2 doses (Group 2: N = 108) of HA vaccine. Associated statistical modeling based on a Bayesian approach of mixed effects models on log transformed titers evaluated three models (linear, piecewise linear, and exponential decay, with and without a natural boosting effect). RESULTS: From the initial cohort, 9 participants (Group 1) and 1 participant (Group 2) showed antibody titers below the seroprotective threshold and received a booster. At Year 10, 190 (Group 1) and 51 (Group 2) participants remained in the study without a booster dose and all were seroprotected. Regarding statistical modeling, the piecewise linear model showed the best fit and demonstrated high and similar seroprotection for each schedule up to 30 years (89% [1-dose schedule], 85% [2-dose schedule]). The 2-dose schedule showed higher GMC (95% CI) than the 1-dose schedule (Year 10: 352 [271-456] versus 78 [69.8-87.6] mIU/mL) and Year 30 (predicted) (37 [13-97] versus 19 [11-34] mIU/mL). Natural boosting had little impact on predicted seroprotection rates at 30 years for the 1-dose schedule (89% [0.8-0.96] and 84% [0.73-0.94] with and without a natural booster, respectively). CONCLUSIONS: Long-term persistence of anti-HAV antibodies was observed up to 10 years with 1-dose and 2-dose vaccine schedules, supporting booster flexibility. Statistical modeling predicted good persistence of seroprotection for each schedule up to 30 years. Natural boosting had a limited impact on seroprotection rate predictions, enabling extrapolation of these results to non-endemic settings for traveler vaccination.

Immunization Against Hepatitis A in Migrant Children: Three Vaccination Strategies, A Retrospective Study.

BACKGROUND: Hepatitis A is endemic in many countries. Swiss guidelines recommend vaccinating patients native from endemic areas. In Geneva's Children's hospital, migrant children are screened and vaccinated if seronegative. Because hepatitis A's prevalence is decreasing worldwide, more children are seronegative at arrival, highlighting the need for immunization in medical centers and refugee camps and questioning the benefits of systematic serology. Other Swiss hospitals vaccinate regardless of serostatus. This study's aim is to assess migrant children's immunity according to origin and age, and the cost-effectiveness of different immunization strategies. METHODS: We retrospectively analyzed 329 children's serostatus (1-16 years of age) between 2012 and 2015, using enzyme-linked fluorescent assay method. Serology and vaccine costs were based on local prices. Groups were compared with χ test and the age-seropositivity relationship was studied with linear regression. RESULTS: The predominant regions were the Eastern Mediterranean and European Regions with mostly negative serologies (71% and 83%) and the African Region with mostly positive serologies (79%). Immunity varied depending on birth country. Regardless of region, seropositivity increased with age (P < 0.001). The most cost-effective vaccination strategy was an individualized approach based on age and origin, reducing costs by 2% compared with serology-guided immunization and by 17% compared with systematic vaccination. CONCLUSIONS: Many migrant children >5 years old are seronegative and at risk of clinical infection. They need to be immunized. New guidelines according to age and origin should be defined to reduce immunization costs. We recommend systematic vaccination for patients <5 years old or native from low endemicity areas (≤25.7% of seropositivity). For the others, we propose serology-based vaccination.

Investigation and analysis of antibody levels of hepatitis A among children before and after implementing the Expanded National Immunization Program in China.

OBJECTIVE: To analyze changes of hepatitis A antibody levels and immunization coverage of HAV vaccine among children before and after implementing the Expanded National Immunization Program in five counties of China, and to provide evidence for developing hepatitis A vaccine immunization strategies. METHODS: 449 children born in 2001, 2005 and 2009 were selected from five counties for an immunization coverage and a sero-prevalence survey of hepatitis A. The chemiluminescence microparticle immunoassays (CMIA) were used to detect hepatitis A IgG antibody and analyzed the factors which influenced the immunization coverage and positive rates. RESULTS: Among 449 subjects of children born in 2001, 2005 and 2009, the immunization coverage were 53.02%, 78.52% and 99.34% (χ2 = 91.285, P < 0.001). The positivity rates of hepatitis A IgG antibody were 61.07%, 81.21%, 95.36% (χ2 = 54.198, P < 0.001), respectively. The immunization coverage and positivity rate significantly increased with the delay of birth year. Children accepting different doses of HA vaccines are significantly different in positive rates of HA antibody, while there are no significant differences of different genders, years of birth, residence types, or types of registered permanent residence in different regions. The positivity rate increased significantly with administration of hepatitis A vaccine and shorter intervals between sample collection and HAV immunization. CONCLUSIONS: After the Expanded National Immunization Program was implemented, hepatitis A antibody levels were significantly increased in five counties, which indicates a successful result of EPI.

Uptake and safety of hepatitis A vaccination during pregnancy: A Vaccine Safety Datalink study.

INTRODUCTION: Infection with hepatitis A virus (HAV) during pregnancy, although uncommon, is associated with gestational complications and pre-term labor. Hepatitis A vaccine (HepA) is recommended for anyone at increased risk for contracting hepatitis A, including women at risk who are also pregnant. Limited data are available on the safety of maternal HepA vaccination. OBJECTIVES: Assess the frequency of maternal HepA receipt and evaluate the potential association between maternal vaccination and pre-specified maternal and infant safety outcomes. METHODS: A retrospective cohort of pregnancies in the Vaccine Safety Datalink (VSD) resulting in live births from 2004 through 2015 was included. Pregnancies with HepA exposure were compared to those with other vaccine exposures, and to those with no vaccine exposures. Risk factors for contracting hepatitis A were identified up to one-year prior to or during the pregnancy using ICD-9 codes. Maternal and fetal adverse events were evaluated according to maternal HepA exposure status. Adjusted odds ratio (OR) were used to describe the association. RESULTS: Among 666,233 pregnancies in the study period, HepA was administered at a rate of 1.7 per 1000 (n = 1140), most commonly within the first six weeks of pregnancy. Less than 3% of those exposed to HepA during pregnancy had an ICD-confirmed risk factor. There were no significant associations between HepA exposure during pregnancy and gestational hypertension, gestational diabetes, pre-eclampsia/eclampsia, cesarean delivery, pre-term delivery, and low birthweight. There was a statistically significant association between HepA exposure during pregnancy and small-for-gestational age (SGA) infants (aOR 1.32, [95% CI 1.09, 1.60], p = 0.004). CONCLUSIONS: The rate of maternal HepA vaccination was low and rarely due to documented risk factors for vaccination. HepA vaccination during pregnancy was not associated with an increased risk for a range of adverse events examined among pregnancies resulting in live births, but an identified association between maternal HepA and SGA infant outcomes, while likely due to unmeasured confounding, warrants further exploration.

Changes in seroprevalence of hepatitis A after the implementation of universal childhood vaccination in Shandong Province, China: A comparison between 2006 and 2014.

OBJECTIVES: The hepatitis A vaccine (HepA) has been included in the national expanded program on immunization (EPI) in China since 2008. This study was performed to evaluate the change in dynamics of the seroepidemiology of hepatitis A virus (HAV) before and after the introduction of the program. METHODS: The trends in seroepidemiology of anti-HAV antibodies were examined in Shandong Province, China, drawing on two population-based samples of persons aged 1-59 years, one obtained in the year 2006 (n = 6682) and the other in 2014 (n = 5095). RESULTS: A dramatic increase in seroprevalence of anti-HAV antibodies from 30.76% (95% confidence interval (CI) 26.24-35.28%) to 77.46% (95% CI 74.04-80.87%) among children aged 1.5-7 years (born after HepA was recommended for routine childhood immunization), as well as an increase from 35.32% (95% CI 29.31-41.33%) to 66.69% (95% CI 55.59-77.80%) in subjects aged 8-14 years, was observed in 2014 when compared with 2006. By contrast, a decline in seroprevalence among subjects aged 15-29 years, as seen particularly in those 20-29 years of age, from 85.72% (95% CI 80.29-91.14%) to 69.24% (95% CI 62.02-76.45%), was found in this study. There was no statistically significant difference in seroprevalence between 2006 and 2014 among the subjects older than 30 years of age. CONCLUSIONS: The national HepA routine immunization program has had a positive effect, leading to an increase in anti-HAV seroprevalence among children in Shandong Province, China. More attention should be paid to young adults in the province.

Characteristics associated with hepatitis B vaccination initiation and completion among adults traveling to a country of high or intermediate endemicity.

BACKGROUND: The hepatitis B (HepB) vaccine is recommended for adults traveling to a country of high or intermediate endemicity. METHODS: Data from the 2016 and 2017 National Health Interview Surveys were pooled. RESULTS: The weighted prevalence of HepB vaccination initiation (≥1 dose) was 37.67% in 2016 (weighted number: 30,581,813/81,192,803) and 40.20% in 2017 (weighted number: 34,509,993/85,849,427). The weighted prevalence of HepB vaccination completion (≥3 doses) was 29.97% in 2016 (weighted number: 24,331,218/81,192,803) and 31.78% in 2017 (weighted number: 27,282,536/ 85,849,427). Characteristics independently associated with HepB vaccination initiation (in descending order by odds ratio) included age, receipt of influenza vaccine, education, ever having lived with someone with hepatitis, class of worker, number of physician visits in the past 12 months, ratio of family income to the poverty threshold, region, sexual orientation, gender, heath insurance, computer use, physical activity, and Hispanic ethnicity. Similar results were found in the analysis for HepB vaccination completion, except that subjects born in the United States showed a higher likelihood of HepB vaccination completion. CONCLUSIONS: HepB vaccination initiation and completion were associated with a number of characteristics that can be utilized to develop strategies to increase HepB vaccination coverage among adults traveling to a country of high or intermediate endemicity.

Characteristics associated with hepatitis A vaccination initiation and completion among adults traveling to a country of high or intermediate endemicity.

BACKGROUND: Hepatitis A (HepA) vaccine is recommended for adults traveling to a country of high or intermediate endemicity. METHODS: The data from the 2016 and 2017 National Health Interview Survey were pooled in this analysis, and the weighted logistic regression model was adopted. RESULTS: Characteristics independently associated with HepA vaccination initiation (≥1 dose) (in descending order by odds ratio) include age, receipt of pneumococcal and influenza vaccine, education, sexual orientation, region, number of physician visits in the past 12 months, physical activity, marital status, computer use, ratio of family income to the poverty threshold, Hispanic ethnicity, and class of worker. Characteristics independently associated with HepA vaccination completion (≥2 doses) (in descending order by odds ratio) include age, receipt of pneumococcal and influenza vaccine, sexual orientation, education, region, marital status, number of physician visits in the past 12 months, ratio of family income to the poverty threshold, physical activity, Hispanic ethnicity, and computer use. CONCLUSIONS: HepA vaccination initiation and completion was associated with a number of characteristics, which can be used to develop strategies to increase HepA vaccination coverage among adults traveling to a country of high or intermediate endemicity.

Immune response to hepatitis A vaccine in patients with HIV.

OBJECTIVES: The aim of this study was to evaluate the impact of various factors that may influence the immunologic response to hepatitis A mono-vaccine or hepatitis A/B co-vaccine (Twinrix®) in HIV-infected patients. DESIGN: Retrospective cross-sectional study. METHODS: HIV positive patients with a full course of hepatitis A vaccine were tested for HAV antibodies. The seroconversion rates were determined, and the influence of several factors including CD4 cell counts, CD4/CD8 ratio, plasma viral load, type of vaccine, and antiretroviral therapy at the time of vaccine, was evaluated. RESULTS: After vaccination, 80.2% of the patients developed anti-HAV antibodies, 81.5% in the mono-vaccine group and 79.2% in the hepatitis A/B co-vaccine group. In the mono-vaccine group, factors significantly associated with a better response to the vaccine were higher CD4 cell count, higher CD4/CD8 ratio, and shorter time interval from vaccine to serological control. In patients who received the hepatitis A/B co-vaccine, younger age and female sex were significantly associated with better vaccine response. Multivariable logistic regression analysis revealed time interval from vaccine to serological control of more than 5 years vs. less than 1 year to be significantly associated with decrease of seroconversion after HAV vaccine. CONCLUSIONS: The response to hepatitis A vaccine is impaired in HIV positive patients. HIV patients, at least those older than 30, should be tested for seroconversion after receiving the hepatitis A vaccine. As hepatitis A titers may rapidly decline, control serology during follow-up should be proposed, possibly within two years. However, vaccine type does not play a role in vaccine response.

Clinical experience with the inactivated hepatitis A vaccine, Avaxim 80U Pediatric.

INTRODUCTION: Hepatitis A, caused by hepatitis A virus (HAV), is primarily transmitted via the fecal/oral route either through ingestion of contaminated food and water or through direct contact with an infectious person. Prevalence of hepatitis A is strongly correlated with socioeconomic factors, decreasing with increased socio-economic development, access to clean water and sanitation. Vaccination against HAV should be part of a comprehensive plan for the prevention and control of viral hepatitis, either as part of regular childhood immunization programs or with other recommended vaccines for travelers. Areas covered: We present here evidence for the immunogenicity and safety of an inactivated HAV pediatric vaccine (Avaxim® 80U Pediatric, Sanofi Pasteur), indicated for use in children aged 12 months to 15 years. Data evaluated are from trials undertaken during the clinical development of this vaccine, a systematic literature review and post-market pharmacovigilance. Expert opinion: The pediatric HAV vaccine is highly immunogenic and generates long-lasting protection against hepatitis A disease in children. The safety and immunogenicity data presented in this review suggest that the pediatric HAV vaccine is a valuable option in the prevention of HAV infection in children in many areas of the world where the disease remains a healthcare issue.

Immunogenicity and side-effects of the inactivated hepatitis A vaccine in periodic fever, aphthous stomatitis, pharyngitis, and adenitis patients.

The aim of this study was to compare the immunogenicity and side-effects of hepatitis A virus (HAV) vaccination between periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) patients and healthy controls who have not been previously exposed to HAV. A prospective observational study was carried out of 28 PFAPA patients and 76 controls who received two doses of the vaccine. Immunogenicity was expressed as seroconversion and seroprotection rates; mean HAV-immunoglobulin G concentration was measured at 0, 1, 7 and 18 months. Side-effects were defined as incidence of adverse events and the effect of vaccination on PFAPA symptoms. All participants were seronegative and seroconverted at 1 month. One month after primary vaccination, 92.9% of PFAPA patients and 77.6% of the controls attained seroprotection, while the rates increased to 100% and 96.1%, respectively, 1 month after the second dose. Seroprotection rates remained adequate 1 year after completion of vaccination. In conclusion, two doses of the inactivated HAV vaccine are well-tolerated and effective in children with PFAPA.

Comparison of the immunogenicity and safety of 3 inactivated hepatitis A vaccines in Korean children aged 12 to 18 months: An open-label, randomized, prospective, multicenter study.

Several approved inactivated hepatitis A (HA) vaccines are available in Korea. These have been shown to be immunogenic and safe in European children; however, their immunogenicity and safety have not been investigated among Korean children. We aimed to compare the immunogenicity and safety of the most commonly used HA vaccines in ethnic Korean children aged 12 to 18 months.In this open-label, randomized, prospective, multicenter study, 108 children were enrolled and randomized to receive a pediatric form of Avaxim, Epaxal, or Havrix. The 2nd dose was administered after an interval of 6 months. Anti-HA virus (HAV) immunoglobulin (Ig) G was measured to assess geometric mean concentrations (GMCs) and seropositvity rates (≥20 mIU/mL anti-HAV IgG). To assess safety, local solicited adverse events (AEs), systemic solicited AEs, unsolicited AEs, and serious AEs (SAEs) were graded.Among the 108 participants enrolled, 37, 34, and 37 received Avaxim, Epaxal, and Havrix, respectively. After administration of 2 doses, the seropositivity rates in the Avaxim, Epaxal, and Havrix groups were all 100% (95% confidence intervals [CIs]: 99.0-100, 98.9-100, and 99.0-100, respectively; P < .001). The anti-HAV GMCs in the Avaxim, Epaxal, and Havrix groups were 5868.4 (95% CI: 4237.2-8126.6), 1962.1 (95% CI: 1298.0-2965.9), and 2232.9 mIU/mL (95% CI: 1428.4-3490.4), respectively, after administration of 2 doses (P < .001). There were no significant differences in the proportions of participants reporting local solicited AEs, systemic solicited AEs, unsolicited AEs, and SAEs among the 3 vaccine groups after the 1st and 2nd doses. All local solicited and unsolicited AEs were grade 1 or 2. Grade 3 systemic solicited AE occurred in 5.4% and 2.9% of the participants in the Havrix group after the 1st and 2nd doses, respectively. SAEs after the 1st and 2nd doses were reported in 2 participants and 1 participant, respectively, but none was assessed as being related to vaccination.The results indicate that these vaccines were safe and immunogenic in ethnic Korean children. The results have contributed to the establishing of an HA vaccination policy in Korea and will be informative to countries that plan to initiate vaccination programs against HAV.

Establishment of an erythropoietin CRS with stable measurable dimer content for SEC system suitability qualification

The European Pharmacopoeia (Ph. Eur.) monograph 1316 'Erythropoietin concentrated solution' prescribes that the dimer content of therapeutic erythropoietin (EPO) preparations must not exceed 2% as determined by Size-Exclusion Chromatography (SEC). This report describes the evaluation of a candidate Chemical Reference Substance (cCRS) to serve as system suitability reference material for the qualification of SEC systems used to assess dimer and oligomer content in EPO solutions. The study organised by the European Directorate for the Quality of Medicines & HealthCare (EDQM) was performed with the participation of six European laboratories which tested the candidate material and the EPO for physicochemical tests CRS batch 1. The candidate material was shown to be a suitable reference material for the determination of the resolving capability of the SEC system for separation of dimer and higher oligomers from monomeric EPO. The cCRS was adopted by the Ph. Eur. Commission as Erythropoietin for SEC system suitability CRS batch 1 following consideration of the report. The importance of the resolving capability of the SEC system, as defined by the peak ratios or the peak-to-valley resolution, together with the asymmetry of the peaks eluted, and the linear response of the UV detector were all seen as critical parameters. Therefore, the monograph Erythropoietin concentrated solution (1316) was revised concomitantly to take account of the CRS and to set acceptance criteria for these critical parameters..