BACKGROUND: Long-lasting protection resulting from hepatitis B vaccine, despite loss of antibody against hepatitis B virus (HBV) surface antigen (anti-HBs), is undetermined. METHODS: We recruited persons from a cohort vaccinated with plasma-derived hepatitis B vaccine in 1981 who have been followed periodically since. We performed serological testing for anti-HBs and microRNA-155 and assessed HBV-specific T-cell responses by enzyme-linked immunospot and cytometric bead array. Study subgroups were defined 32 years after vaccination as having an anti-HBs level of either ≥10 mIU/mL (group 1; n = 13) or <10 mIU/mL (group 2; n = 31). RESULTS: All 44 participants, regardless of anti-HBs level, tested positive for tumor necrosis factor alpha, interleukin 10, or interleukin 6 production by HBV surface antigen-specific T cells. The frequency of natural killer T cells correlated with the level of anti-HBs (P = .008). The proportion of participants who demonstrated T-cell responses to HBV core antigen varied among the cytokines measured, suggesting some natural exposure to HBV in the study group. No participant had evidence of breakthrough HBV infection. CONCLUSIONS: Evidence of long-lasting cellular immunity, regardless of anti-HBs level, suggests that protection afforded by primary immunization with plasma-derived hepatitis B vaccine during childhood and adulthood lasts at least 32 years.

BACKGROUND: The duration of protection in children and adults resulting from hepatitis B vaccination is unknown. In 1981, we immunized a cohort of 1578 Alaska Native adults and children from 15 Alaska communities aged ≥6 months using 3 doses of plasma-derived hepatitis B vaccine. METHODS: Persons were tested for antibody to hepatitis B surface antigen (anti-HBs) levels 30 years after receiving the primary series. Those with levels <10 mIU/mL received 1 booster dose of recombinant hepatitis B vaccine 2-4 weeks later and were then evaluated on the basis of anti-HBs measurements 30 days after the booster. RESULTS: Among 243 persons (56%) who responded to the original primary series but received no subsequent doses during the 30-year period, 125 (51%) had an anti-HBs level ≥10 mIU/mL. Among participants with anti-HBs levels <10 mIU/mL who were available for follow-up, 75 of 85 (88%) responded to a booster dose with an anti-HBs level ≥10 mIU/mL at 30 days. Initial anti-HBs level after the primary series was correlated with higher anti-HBs levels at 30 years. CONCLUSIONS: Based on anti-HBs level ≥10 mIU/mL at 30 years and an 88% booster dose response, we estimate that ≥90% of participants had evidence of protection 30 years later. Booster doses are not needed.

BACKGROUND: Hepatitis B antibody persistence was assessed in individuals who had previously received a vaccine booster. METHODS: We measured hepatitis B surface antigen antibody (anti-HBs) levels 7-9 years post-hepatitis B booster in individuals with primary vaccination at birth. RESULTS: While 95 (91.3%) of 104 participants had detectable anti-HBs (minimum 0.1 mIU/mL, maximum 1029 mIU/mL), only 43 (41%) had protective levels ≥10mIU/mL. Pre- and four week post-booster anti-HBs levels were significant predictors of hepatitis B immunity at follow-up (P <0.001). CONCLUSIONS: Almost all participants had detectable anti-HBs 7-9 years after hepatitis B vaccine booster, but less than half had levels ≥10mIU/mL.

BACKGROUND: Hepatitis A is mostly a self-limiting disease but causes substantial economic burden. Consequently, United States Advisory Committee for Immunization Practices recommends inactivated hepatitis A vaccination for all children beginning at age 1 year and for high risk adults. The hepatitis A vaccine is highly effective but the duration of protection is unknown. METHODS: We examined the proportion of children with protective hepatitis A antibody levels (anti-HAV ≥20mIU/mL) as well as the geometric mean concentration (GMC) of anti-HAV in a cross sectional convenience sample of individuals aged 12-24 years, who had been vaccinated with a two-dose schedule in childhood, with the initial dose at least 5 years ago. We compared a subset of data from persons vaccinated with two-doses (720 EL.U.) at age 3-6 years with a demographically similar prospective cohort that received a three-dose (360 EL.U.) schedule and have been followed for 17 years. RESULTS: No significant differences were observed when comparing GMC between the two cohorts at 10 (P=0.467), 12 (P=0.496), and 14 (P=0.175) years post-immunization. For the three-dose cohort, protective antibody levels remain for 17 years and have stabilized leveled-off over the past 7 years. CONCLUSION: The two- and three-dose schedules provide similar protection >14 years after vaccination, indicating a booster dose is not needed at this time. Plateauing anti-HAV GMC levels suggest protective antibody levels may persist long-term.

BACKGROUND: Helicobacter pylori (H. pylori) infection has been correlated with low serum ferritin and iron deficiency. As a secondary analysis of a study of H. pylori reinfection, we investigated the association of H. pylori infection and the effect of its eradication on serum ferritin and iron deficiency. METHODS: Alaska Native adults undergoing esophagogastroduodenoscopy had sera collected and a (13) C urea breath test (UBT) was performed. Those H. pylori positive were treated with an antibiotic regimen; those who tested negative 2 months after treatment were evaluated at 4, 6, 12, and 24 months by UBT and serum ferritin with an immunoradiometric assay. We excluded persons from further analysis if they were prescribed iron by their provider. RESULTS: We measured serum ferritin for 241 persons; 121/241 were H. pylori positive. The geometric mean ferritin (GMF) for persons with and without H. pylori infection was 37 mcg/L and 50 mcg/L, respectively (p = .04). At enrollment, 19/121 H. pylori-positive persons had iron deficiency compared with 8/120 H. pylori negative (p = .02). Among 66 persons tested at 24 months, the GMF was higher at 24 months (49.6 mcg/L) versus enrollment (36.5 mcg/L; p = .02). Six of 11 persons with iron deficiency at enrollment no longer had iron deficiency and had a higher GMF (p = .02) 24 months after treatment. CONCLUSIONS: H. pylori infection was correlated with lower serum ferritin and iron deficiency. After H. pylori eradication, serum ferritin increased and approximately half of persons resolved their iron deficiency. Testing for H. pylori infection and subsequent treatment of those positive could be considered in persons with unexplained iron deficiency.

CDC recommends hepatitis A vaccination for all children at age 1 year and high risk adults. The vaccine is highly effective; however, protection duration is unknown. We report hepatitis A antibody concentrations 17 years after childhood immunization, demonstrating protective antibody levels remain and have stabilized over the past 7 years.

BACKGROUND: Older adults are at highest risk of invasive pneumococcal disease (IPD) and are recommended to receive vaccination with 23-valent pneumococcal polysaccharide vaccine (PPV23). Antibody concentrations decline following vaccination. We evaluated the immunogenicity and reactogenicity of revaccination and repeat revaccination. METHODS: Adults aged 55-74 years were vaccinated with a 1st to 4th dose of PPV23. Participants were eligible for revaccination if a minimum of 6 years had passed since their last dose of PPV23. Blood collected on the day of vaccination and 30 days later was analyzed by ELISA for IgG to five serotypes. Functional antibody activity was measured using an opsonophagocytic killing (OPK) assay. Reactions to vaccination were documented. RESULTS: Subjects were vaccinated with a 1st dose (n=123), 2nd dose (n=121), or 3rd or 4th dose (n=71) of PPV23. The post-vaccination IgG geometric mean concentrations (GMCs) were similar among first-time vaccinees and re-vaccinees for all serotypes with the exception of a lower GMC for serotype 1 in re-vaccinees. The post-vaccination OPK geometric mean titers (GMTs) were similar among first-time vaccinees and re-vaccinees with the exception of a higher GMT for serotype 6B in re-vaccinees. Compared to first-time vaccinees, re-vaccinees reported more joint pain (p=0.003), fatigue (p=0.027), headache (p=0.011), swelling (p=0.009), and moderate limitation in arm movement (p=0.015). CONCLUSIONS: Repeat revaccination with PPV23, administered 6 or more years after the prior dose, was immunogenic and generally well tolerated.

We conducted a 10-15 years follow-up to a long-term prospective cohort study on the immunogenicity of inactivated hepatitis A vaccine in Alaska Native children, who were initially vaccinated between 3-6 years of age. Children received three vaccine doses (320 E.U.) and were randomized into the following vaccination schedules: A (0, 1, 2 months); B (0, 1, 6 months); and C (0, 1, 12 months). Sera were collected every 2 years and tested for hepatitis A virus (anti-HAV). Levels 20 mIU/mL were considered protective. Anti-HAV geometric mean concentrations were compared by vaccination schedule at 10, 12 and 14 years of follow-up, using ANOVA. Antibody decline over the entire 15-year follow-up period was also analyzed. While none of the inter-schedule comparisons differed significantly from each other at the 10, 12 and 14-year periods, schedules B and C had significantly higher anti-HAV levels than schedule A over the entire 15 years of the study (P0.01). All schedule B and C children maintained seroprotective levels in all follow-up periods. Fourteen percent of schedule A children fell below seroprotective levels at 14 years. Our model estimated that anti-HAV geometric mean concentrations would fall below seroprotective levels at 26, 30 and 32 years for schedules A, B and C, respectively. The data indicate that hepatitis A immunity lasts at least 15 years after vaccination in children and that a booster dose is not needed during that time. However, continued monitoring is necessary to assess the need for a booster dose later in the second and third decade after receipt of the primary series.

BACKGROUND: The duration of protection in children and adults (including health care workers) resulting from the hepatitis B vaccine primary series is unknown. METHODS: To determine the protection afforded by hepatitis B vaccine, Alaska Native persons who had received plasma-derived hepatitis B vaccine when they were >6 months of age were tested for antibody to hepatitis B surface antigen (anti-HBs) 22 years later. Those with levels <10 mIU/mL received 1 dose of recombinant hepatitis B vaccine and were evaluated on the basis of anti-HBs measurements at 10-14 days, 30-60 days, and 1 year. RESULTS: Of 493 participants, 60% (298) had an anti-HBs level 10 mIU/mL. A booster dose was administered to 164 persons, and 77% responded with an anti-HBs level 10 mIU/mL at 10-14 days, reaching 81% by 60 days. Response to a booster dose was positively correlated with younger age, peak anti-HBs response after primary vaccination, and the presence of detectable anti-HBs before boosting. Considering persons with an anti-HBs level 10 mIU/mL at 22 years and those who responded to the booster dose, protection was demonstrated in 87% of the participants. No new acute or chronic hepatitis B virus infections were identified. CONCLUSIONS: The protection afforded by primary immunization with plasma-derived hepatitis B vaccine during childhood and adulthood lasts at least 22 years. Booster doses are not needed.