The efficacy of two different dosages of hepatitis B immunoglobulin combined with hepatitis B vaccine in preventing mother-to-child transmission of hepatitis B virus: A prospective cohort study

Background/aimsA birth dose of hepatitis B immunoglobulin (HBIG), in combination with hepatitis B vaccine (HepB), is recommended for infants born to hepatitis B surface antigen (HBsAg)-positive mothers. However, the optimal dosage of HBIG remains to be resolved. This prospective cohort study aimed to compare the efficacy of two dosages of HBIG combined with HepB to prevent mother-to-child transmission (MTCT) of HBV.MethodsFrom 2009 to 2011, we prospectively enrolled mother-infant pairs with positive maternal HBsAg in China. Infants were assigned to receive one dose of 100 IU or 200 IU HBIG within 12 h of birth according to maternal numbering, followed by completion of the 3-dose 10 μg HepB series. At 7 months, post-vaccination serologic testing (PVST) was performed in 545 and 632 infants in 100 IU and 200 IU HBIG groups, respectively, among whom, 451 and 529 were followed up to 12 months.ResultsMaternal and birth characteristics were comparable between infants in 100 IU and 200 IU HBIG groups. At 7 months, the rates of perinatal infection were 1.5% (8/545) and 1.9% (12/632) in 100 IU and 200 IU HBIG groups, respectively (p = .568). One non-responder infant in 200 IU HBIG group became newly infected at 12 months. The antibody to hepatitis B surface antigen (anti-HBs) positive rates were 98.5% (529/537) and 98.2% (609/620) in 100 IU and 200 IU HBIG groups at 7 months, respectively (p = .704), and the corresponding figures were 98.2% (431/439) and 97.1% (496/511) at 12 months (p = .266). The anti-HBs geometric mean concentrations were comparable between two groups at 7 months (707.95 mIU/mL vs. 602.56 mIU/mL, p = .062) and 12 months (245.47 mIU/mL vs. 229.09 mIU/mL, p = .407).ConclusionsOne birth dose of 100 IU HBIG, combined with the HepB series, might be enough for preventing MTCT of HBV in infants born to HBsAg-positive mothers.     

Targeted outreach hepatitis B vaccination program in high-risk adults: The fundamental challenge of the last mile

BackgroundThe aim of this study was to evaluate the cost-effectiveness of the on-going decentralised targeted hepatitis B vaccination program for behavioural high-risk groups operated by regional public health services in the Netherlands since 1-November-2002. Target groups for free vaccination are men having sex with men (MSM), commercial sex workers (CSW) and hard drug users (HDU). Heterosexuals with a high partner change rate (HRP) were included until 1-November-2007.MethodsBased on participant, vaccination and serology data collected up to 31-December-2012, the number of participants and program costs were estimated. Observed anti-HBc prevalence was used to estimate the probability of susceptible individuals per risk-group to become infected with hepatitis B virus (HBV) in their remaining life. We distinguished two time-periods: 2002–2006 and 2007–2012, representing different recruitment strategies and target groups. Correcting for observed vaccination compliance, the number of future HBV-infections avoided was estimated per risk-group. By combining these numbers with estimates of life-years lost, quality-of-life losses and healthcare costs of HBV-infections - as obtained from a Markov model-, the benefit of the program was estimated for each risk-group separately.ResultsThe overall incremental cost-effectiveness ratio of the program was €30,400/QALY gained, with effects and costs discounted at 1.5% and 4%, respectively. The program was more cost-effective in the first period (€24,200/QALY) than in the second period (€42,400/QALY). In particular, the cost-effectiveness for MSM decreased from €20,700/QALY to €47,700/QALY.Discussion and conclusionThis decentralised targeted HBV-vaccination program is a cost-effective intervention in certain unvaccinated high-risk adults. Saturation within the risk-groups, participation of individuals with less risky behaviour, and increased recruitment investments in the second period made the program less cost-effective over time. The project should therefore discus how to reduce costs per risk-group, increase effects or when to integrate the vaccination in regular healthcare.     

Evaluation of a convenient vaccination schedule against hepatitis B in HIV-patients with undetectable HIV viral load

Vaccination against hepatitis B virus (HBV) is recommended for all HIV-positive individuals but the standard schedule is not satisfactory. High or more doses have also been studied with variable results. We compared a vaccination schedule with a higher dose but fewer shots to the standard scheme (HBVaxPro 40 μg versus Engerix 20 μg at 0, 1, and 6 months). Of the 63 patients vaccinated with HBVaxPro 79%, 65% and 47% seroconverted at month 1, 12 and 24 after vaccination, respectively. A total of 137 patients received Engerix and showed lower response rates (68%, 53% and 38%, respectively). Anti-HBs titers in the Engerix group were also lower with a statistically significant difference.In patients younger than 55 years HBVaxPro was 3 times more likely to provoke a response compared with Engerix (OR = 3, p = 0.006). In conclusion, HBVaxPro 40 μg at 3 doses could be proposed as a more robust and acceptable alternative.     

Vaccine Adjuvant Systems containing monophosphoryl lipid A and QS-21 induce strong humoral and cellular immune responses against hepatitis B surface antigen which persist for at least 4 years after vaccination

BackgroundRecombinant hepatitis B surface antigen (HBsAg) was used as a model antigen to evaluate persistence of cellular and humoral immune responses when formulated with three different Adjuvant Systems containing 3-O-desacyl-4′-monophosphoryl lipid A (MPL) and QS-21, in an oil-in-water emulsion (AS02_B and AS02_V), or with liposomes (AS01_B).MethodsThis is an open, 4-year follow-up of a previous randomised, double-blind study. Healthy subjects aged 18–40 years received three vaccine doses on a month 0, 1, 10 schedule and were initially followed for 18 months. A total of 93 subjects (AS02_B: n = 30; AS02_V: n = 28; AS01_B: n = 35) were enrolled in this follow-up and had an additional blood sample taken at Year 4 (NCT02153320). The primary endpoint was the frequency of HBsAg-specific CD4⁺ and CD8⁺ T-cells expressing cytokines upon short-term in vitro stimulation of peripheral blood mononuclear cells with HBsAg-derived peptides. Secondary endpoints were anti-HBs antibody titres and frequency of HBsAg-specific memory B-cells.ResultsA strong and persistent specific CD4⁺ T-cell response was observed at Year 4 in all groups. HBsAg-specific CD4⁺ T-cells expressed mainly CD40L and IL-2, and to a lesser extent TNF-α and IFN-γ. HBsAg-specific CD8⁺ T-cells were not detected in any group. A high, persistent HBsAg-specific humoral immune response was observed in all groups, with all subjects seroprotected (antibody titre ≥10 mIU/mL) at Year 4. The geometric mean antibody titre at Year 4 was above 100,000 mIU/mL in all groups. A strong memory B-cell response was observed post-dose 2, which tended to increase post-dose 3 and persisted at Year 4 in all groups.ConclusionThe MPL/QS-21/HBsAg vaccine formulations induced persistent immune responses up to 4 years after first vaccination. These Adjuvant Systems offer potential for combination with recombinant, synthetic or highly purified subunit vaccines, particularly for vaccination against challenging diseases, or in specific populations, although additional studies are needed.     

Strong influence of human leukocyte antigen-DP variants on response to hepatitis B vaccine in a Japanese population

Genome-wide association studies (GWASs) have reported that human leukocyte antigen (HLA) variants are associated with chronic hepatitis B, spontaneous hepatitis B virus (HBV) clearance, and response to hepatitis B vaccine. Single nucleotide polymorphisms (SNPs) in HLA-DP (rs9277535 and rs3077) and HLA-DQ (rs2856718 and rs7453920) have been repeatedly associated with chronic hepatitis B and spontaneous HBV clearance. However, the data on the SNPs associated with response to hepatitis B vaccine are inconclusive. The objective of this study was to determine whether these four HLA SNPs that have been identified as risk loci for chronic HBV infection are associated with response to hepatitis B vaccine in a Japanese population. We enrolled 278 medical students who received hepatitis B vaccination and measured anti-hepatitis B surface (HBs) antibody titers 1 month after a three-dose vaccination series. We found that rs9277535 and rs3077 in HLA-DP were strongly associated with response to hepatitis B vaccine (odds ratio [OR] = 0.31 and 0.32, P = 0.004 and 0.010, respectively). These two SNPs were significantly associated with anti-HBs titers in an allele-dependent manner. On the other hand, rs2856718 and rs7453920 in HLA-DQ were not associated with response to hepatitis B vaccine. These results indicate that rs9277535 and rs3077 in HLA-DP are the major determinants of response to hepatitis B vaccine, whereas rs2856718 and rs7453920 in HLA-DQ have little effect on the immune response to hepatitis B vaccine.     

Cost-effectiveness analysis of catch-up hepatitis A vaccination among unvaccinated/partially-vaccinated children

BackgroundSince 2006, the US Centers for Disease Control and Prevention has recommended hepatitis A (HepA) vaccination routinely for children aged 12–23 months to prevent hepatitis A virus (HAV) infection. However, a substantial proportion of US children are unvaccinated and susceptible to infection. We present results of economic modeling to assess whether a one-time catch-up HepA vaccination recommendation would be cost-effective.MethodsWe developed a Markov model of HAV infection that followed a single cohort from birth through death (birth to age 95 years). The model compared the health and economic outcomes from catch-up vaccination interventions for children at target ages from two through 17 years vs. outcomes resulting from maintaining the current recommendation of routine vaccination at age one year with no catch-up intervention.ResultsOver the lifetime of the cohort, catch-up vaccination would reduce the total number of infections relative to the baseline by 741 while increasing doses of vaccine by 556,989. Catch-up vaccination would increase net costs by $10.2 million, or $2.38 per person. The incremental cost of HepA vaccine catch-up intervention at age 10 years, the midpoint of the ages modeled, was $452,239 per QALY gained. Across age-cohorts, the cost-effectiveness of catch-up vaccination is most favorable at age 12 years, resulting in an Incremental Cost-Effectiveness Ratio of $189,000 per QALY gained.ConclusionsGiven the low baseline of HAV disease incidence achieved by current vaccination recommendations, our economic model suggests that a catch-up vaccination recommendation would be less cost-effective than many other vaccine interventions, and that HepA catch-up vaccination would become cost effective at a threshold of $50,000 per QALY only when incidence of HAV rises about 5.0 cases per 100,000 population.     

Evaluation of storing hepatitis B vaccine outside the cold chain in the Solomon Islands: Identifying opportunities and barriers to implementation

Monovalent Hepatitis B vaccine (HepB) is heat stable, making it suitable for storage outside cold chain (OCC) at 37 °C for 1 month. We conducted an OCC project in the Solomon Islands to determine the feasibility of and barriers to national implementation and to evaluate impact on coverage. Healthcare workers at 13 facilities maintained monovalent HepB birth dose (HepB-BD) OCC for up to 28 days over 7 months. Vaccination data were recorded for children born during the project and those born during 7 months before the project. Timely HepB-BD coverage among facility and home births increased from 30% to 68% and from 4% to 24%, respectively. Temperature excursions above 37 °C were rare, but vaccine wastage was high and shortages common. Storing HepB OCC can increase HepB-BD coverage in countries with insufficient cold chain capacity or numerous home births. High vaccine wastage and unreliable vaccine supply must be addressed for successful implementation.     

Maternal Tdap vaccination and risk of infant morbidity

IntroductionAn increased risk of diagnosed chorioamnionitis in women vaccinated with Tdap during pregnancy was previously detected at two Vaccine Safety Datalink (VSD) sites. The clinical significance of this finding related to infant outcomes remains uncertain.MethodsRetrospective cohort study of singleton live births born to women who were continuously insured from 6 months prior to their last menstrual period through 6 weeks postpartum, with ≥1 outpatient visit during pregnancy from January 1, 2010 to November 15, 2013 at seven integrated United States health care systems part of the VSD. We re-evaluated the association between maternal Tdap and chorioamnionitis and evaluated whether specific infant morbidities differ among infants born to mothers who did and did not receive Tdap during pregnancy. We focused on 2 Tdap exposure windows: the recommended 27–36 weeks gestation or anytime during pregnancy. We identified inpatient diagnostic codes for transient tachypnea of the newborn (TTN), neonatal sepsis, neonatal pneumonia, respiratory distress syndrome (RDS), and newborn convulsions associated with an infant's first hospitalization. A generalized linear model with Poisson distribution and log-link was used to estimate propensity score adjusted rate ratios (ARR) with 95% confidence intervals (CI).ResultsThe analyses included 197,564 pregnancies. Chorioamnionitis was recorded in 6.4% of women who received Tdap vaccination any time during pregnancy and 5.2% of women who did not (ARR [95% CI]: 1.23 [1.17, 1.28]). Compared with unvaccinated women, there were no significant increased risks (ARR [95% CI]) for TTN (1.04 [0.98, 1.11]), neonatal sepsis (1.06 [0.91, 1.23]), neonatal pneumonia (0.94 [0.72, 1.22]), RDS (0.91 [0.66, 1.26]), or newborn convulsions (1.16 [0.87, 1.53]) in infants born to Tdap-vaccinated women.Conclusions and RelevanceDespite an observed association between maternal Tdap vaccination and maternal chorioamnionitis, we did not find increased risk for clinically significant infant outcomes associated with maternal chorioamnionitis.     

Serotype-specific immune responses to pneumococcal conjugate vaccine among children are significantly correlated by individual: Analysis of randomized controlled trial data

BackgroundThe magnitude of an individual’s serotype-specific immunoglobulin G (IgG) response to a pneumococcal conjugate vaccine (PCV) has been associated with the vaccine’s protective efficacy against carriage of pneumococci of that serotype, though the relationship with other serotypes needs to be understood.MethodsUsing immunogenicity data collected during a trial comparing the 7-valent (PCV7) and 13-valent (PCV13) vaccines, we measured associations between serotype-specific IgG levels, and used multiple regressions to identify demographic predictors of response.ResultsVaccine-induced IgG levels were moderately positively correlated with one another, with pairwise correlation coefficients of 0.40–0.70. Principal component analysis of vaccine-serotype responses yielded one principal component indicating general immune responsiveness, and a second principal component mainly describing responses to serotype 14, which was the least correlated with the other responses. Overall, demographic variables explained only 17.0 and 20.4% of the geometric mean PCV7 and PCV13 responses, respectively. In both groups, older age at the first vaccine dose and shorter time from vaccination to antibody measurement were independently associated with stronger geometric mean responses.DiscussionImproved understanding of the nature and causes of variation in immune response may aid in optimizing vaccination schedules and identifying robust correlates of protection.     

Influenza vaccination responses: Evaluating impact of repeat vaccination among health care workers

ObjectiveTo compare the antibody response to influenza between health care workers (HCWs) who have received multiple vaccinations (high vaccination group) and those who have received fewer vaccinations (low vaccination group).DesignProspective serosurvey.SettingTertiary referral hospital.ParticipantsHealthcare workers.MethodsHealthcare workers were vaccinated with the 2015 southern hemisphere trivalent influenza vaccine. Influenza antibody titres were measured pre-vaccination, 21–28 days post-vaccination and 6 months post-vaccination. Antibody titres were measured using the haemagglutination inhibition assay. Levels of seropositivity and estimated geometric mean titres were calculated.ResultsOf the 202 HCWs enrolled, 182 completed the study (143 high vaccination and 39 low vaccination). Both vaccination groups demonstrated increases in post-vaccination geometric mean titres, with greater gains in the low vaccination group. Seropositivity remained high in both high and low vaccination groups post-vaccination. The highest fold rise was observed among HCWs in the low vaccination group against the H3N2 component of the vaccine.ConclusionsBoth high and low vaccination groups in our study demonstrated protective antibody titres post-vaccination. The findings from the current study are suggestive of decreased serological response among highly vaccinated HCWs. More studies with larger sample sizes and a greater number of people in the vaccine-naïve and once-vaccinated groups are required to confirm or refute these findings before making any policy changes.     

Age-dependent immune responses and immune protection after avian coronavirus vaccination

Infectious bronchitis virus (IBV) is an endemic disease of chickens and a major contributor to economic losses for the poultry industry despite vaccination. Recent observations indicated that chicks may have an immature immune system immediately after hatching when vaccinated for IBV. Therefore we hypothesized that early IBV vaccination will generate an immature, poorly protective IBV-specific immune response contributing to immune escape and persistence of IBV. To test this hypothesis the IBV-specific immune response and immune protection were measured in chicks vaccinated at different ages. This demonstrated a delayed production of IgG and IgA plasma antibodies in the 1, 7 and 14-day-old vaccination groups and also lower IgA antibody levels were observed in plasma of the 1-day-old group. Similar observations were made for antibodies in tears. In addition, IgG antibodies from the 1-day-old group had lower avidity indices than day 28 vaccinated birds. The delayed and/or lower antibody response combined with lower IgG avidity indices coincided with increased tracheal inflammation and depletion of tracheal epithelia cells and goblet cells upon IBV field strain challenge. The lack of vaccine-mediated protection was most pronounced in the 1-day-old vaccination group and to a lesser extent the 7-day-old group, while the 14-day-old and older chickens were protected. These data strongly support IBV vaccination after day 7 post hatch.     

Investigation of group A Streptococcus immune responses in an endemic setting,with a particular focus on J8

Sustained control of group A Streptococcus (GAS) infections in settings of poverty has proven to be challenging, and an effective vaccine may be the most practical long-term strategy to reduce GAS-related disease burden. Candidate GAS vaccines based on the J8 peptide have demonstrated promising immunogenicity in mice, however, less is known about the role of J8 antibodies in the human immune response to GAS infection. We analysed the stimulation of J8 antibodies in response to infection, and the role of existing J8 antibodies in protection against subsequent infection, using data collected in the Fijian population: (1) cross sectional population serosurvey; (2) paired serum collection for assessment of M-specific and J8 antibody responses; and (3) longitudinal assessment of GAS infection and immunity. Median J8 antibody concentrations peaked in the 5–14 year age group, but there was no sustained increase with age. J8 antibody concentration was neither a significant predictor of time to next infection, nor did it show any relationship to the time since last recorded skin infection. Similarly, J8 antibody fold changes over a defined period were associated neither with the time since last skin infection, nor the number of intervening skin infections. While strong M-specific antibody responses were observed for skin infection, similarly strong J8 antibody responses were not observed. There is no indication that antibodies to the J8 antigen would be useful as either a marker of GAS infection or a measure of population immunity, with J8 antibody responses to infection fleeting, if existent at all.     

Allergic patients with and without allergen-specific immunotherapy mount protective immune responses to tick-borne encephalitis vaccination in absence of enhanced side effects or propagation of their Th2 bias

BackgroundAllergic diseases are caused by Th2-driven immune responses and their treatment with specific immunotherapy (SIT) leads to immunomodulation via IL10, TGF-ß and Th1/Tr1 shift. This phase IV, open-label clinical trial investigated whether allergies and SIT treatment influenced immune responses to routine vaccination.MethodsWe studied three groups: 49 allergic patients (allergic group), 21 allergic patients receiving maintenance doses of SIT (SIT group), and 49 non-allergic controls. All subjects received tick-borne encephalitis (TBE) booster vaccines and humoral and cellular immune responses were evaluated after one week, four weeks and six months.ResultsThe levels and kinetics of neutralizing TBE-specific antibodies, reflecting protection against TBE, were not significantly different in the three groups. The allergic group showed Th2 polarization pre-booster as indicated by increased TBE-specific IgG1 and elevated mitogen-induced IL5 production. Alum-adjuvanted TBE vaccine led to Th2 biased immune responses in the controls, but to no further enhancement of Th2 polarization in the allergic and SIT group. Furthermore, in the SIT group cellular parameters reflected the induction of immunomodulation due to increased Tregs, elevated baseline IL10 and lack of TBE-specific IL5. Importantly, these cellular regulatory responses did not limit the ability to mount sufficient TBE-specific antibodies after the booster. All groups tolerated the vaccine well with no exacerbation of allergic symptoms.ConclusionTBE booster vaccinations were immunogenic and safe in both the allergic and SIT group and contributed to balanced immune responses. Our data indicate that all allergic patients, even when undergoing SIT, should be vaccinated without hesitation and at regular intervals according to standard recommendations.ClinicalTrials.gov (NCT02511535).     

Fibroblast-stimulating lipopeptide-1 as a potential mucosal adjuvant enhances mucosal and systemic immune responses to enterovirus 71 vaccine

To prevent viral infection at the site of entry, mucosal vaccines are potent tools for inducing IgA secretion for defense. Because Toll-like receptor (TLR) ligands serve as strong adjuvants, two ligands that mimic the structure of mycoplasmal and bacterial lipopeptides represent interesting vaccine candidates. Pam3CSK4, a synthetic triacylated lipopeptide, interacts with TLR2/1. Because fibroblast-stimulating lipopeptide-1 (FSL-1), a synthetic diacylated lipopeptide, is recognized by TLR2/6, we targeted the potential immuno-inducibility of Pam3CSK4 and FSL-1 as adjuvants of an enterovirus 71 (EV71) mucosal vaccine. Naïve BALB/c mice were used for intranasal immunization three times over a 3-week interval, with results showing that EV71-specific IgG and IgA in serum, nasal washes, bronchoalveolar lavage fluid, and feces from the EV71 + FSL-1 group were significantly higher than levels observed in mice treated with EV71 + Pam3CSK4, EV71 alone, or the control group treated with phosphate-buffered saline. Furthermore, we observed more EV71-specific IgG and IgA-producing cells in treatments using EV71 formulated with FSL-1. Additionally, T cell-proliferative responses and interferon-γ and interleukin-17 secretion were significantly increased when inactivated EV71 was formulated using FSL-1. Moreover, serum from immunized mice was capable of neutralizing the infectivity of EV71 (C2 genotype) and was able to cross-neutralize the B4 and B5 genotypes of EV71. Our data suggested that FSL-1 could be used as an efficient adjuvant for intranasal EV71-vaccine immunization.     

Prevention of perinatal hepatitis B transmission in Haimen City,China: Results of a community public health initiative

In regions where hepatitis B virus (HBV) is endemic, perinatal transmission is common. Infected newborns have a 90% chance of developing chronic HBV infection, and 1 in 4 will die prematurely from HBV-related liver disease. In 2010, the Hepatitis B Foundation and the Haimen City CDC launched the Gateway to Care campaign in Haimen City, China to improve awareness, prevention, and control of HBV infection citywide. The campaign included efforts to prevent perinatal HBV transmission by screening all pregnant women for hepatitis B surface antigen (HBsAg), following those who tested positive, and administering immunoprophylaxis to their newborns at birth. Of 5407 pregnant women screened, 185 were confirmed HBsAg-positive and followed until delivery. At age one, 175 babies were available for follow up testing. Of those, 137 tested negative for HBsAg and positive for antibodies to HBsAg, indicating protection. An additional 34 HBsAg-negative babies also tested negative for antibodies to HBsAg or had indeterminate test results, were considered to have had inadequate immune responses to the vaccine, and were given a booster dose. A higher prevalence of nonresponse to HBV vaccine was observed among babies born to hepatitis B e antigen (HBeAg)-positive mothers and mothers with high HBV DNA titers. The remaining 4 babies tested positive for HBsAg and negative for antibodies, indicative of active HBV infection. The mothers of all 4 had viral loads ≥8 × 10⁶ copies/ml in the third trimester. Although inadequate response or nonresponse to HBV vaccine was more common among babies born to HBeAg-positive and/or high viral load mothers, these risk factors did not completely predict nonresponsiveness. All babies born to HBV-infected mothers should be tested upon completion of the vaccine series to ascertain adequate protection. Some babies of HBeAg-positive mothers with high viral load may still become HBV infected despite timely immunoprophylaxis with HBV vaccine and HBIG.     

Methotrexate reduces vaccine-specific immunoglobulin levels but not numbers of circulating antibody-producing B cells in rheumatoid arthritis after vaccination with a conjugate pneumococcal vaccine

BackgroundTreatment with methotrexate (MTX) in patients with rheumatoid arthritis (RA) leads to decreased total immunoglobulin (Ig) levels and impairs vaccine-specific IgG antibody levels following pneumococcal vaccination. The mechanisms by which MTX exerts these effects in RA are unknown. We aimed to evaluate whether MTX reduces vaccine-specific serum Ig levels and their functionality in RA patients following vaccination with pneumococcal conjugate vaccine, and if numbers of antigen-specific circulating plasmablasts are affected.MethodsTen patients with RA on MTX and 10 RA patients without disease modifying anti-rheumatic drug (DMARD) were immunized with a dose 13-valent pneumococcal conjugate vaccine (Prevenar13). Circulating plasmablasts producing total IgG and IgA as well as specific IgG and IgA against two pneumococcal capsular serotypes (6B and 23F) were enumerated using ELISPOT 6 days after vaccination. IgG levels against both these serotypes were determined with ELISA before and 4–6 weeks after vaccination. Positive antibody response was defined as ⩾2-fold increase of pre-vaccination antibody levels. The functionality of vaccine specific antibodies to serotype 23F was evaluated by measuring their ability to opsonize bacteria using opsonophagocytic assay (OPA) in 4 randomly chosen RA patients on MTX and 4 RA patients without DMARD.ResultsAfter vaccination, RA patients on MTX showed significant increase in pre- to postvaccination antibody levels for 6B (p < 0.05), while patients without DMARD had significant increases for both 6B and 23F (p < 0.05 and p < 0.01, respectively). Only 10% of RA on MTX and 40% of RA patients without DMARD showed positive post-vaccination antibody responses for both serotypes. Increased opsonizing ability after vaccination was detected in 1 of 4 RA patients on MTX and 3 of 4 patients on RA without DMARD. However, numbers of circulating total and vaccine-specific IgG- or IgA-producing plasmablasts did not differ between RA patients with or without MTX.ConclusionsMTX treatment in RA leads to reduced vaccine-specific antibody responses and their functionality compared to untreated RA following pneumococcal vaccination using polysaccharide-protein conjugate vaccine. However, since there was no reduction in numbers of circulating total or vaccine-specific antibody-producing plasmablasts after vaccination this effect is probably not due to reduced activation of B cells in lymphoid tissue.Clinical trial registration: NCT02240888.     

Association between patient reminders and influenza vaccination status among children

BackgroundPatient reminders are recommended to increase vaccination rates. The objectives of this study were to estimate the percentage of children 6 months–17 years for whom a patient reminder for influenza vaccination was received by a child’s parent or guardian, estimate influenza vaccination coverage by receipt of a patient reminder, and identify factors associated with receipt of a patient reminder.MethodsNational Immunization Survey-Flu (NIS-Flu) data for the 2013–14 influenza season were analyzed. Tests of association between patient reminders and demographic characteristics were conducted using Wald chi-square tests and pairwise comparison t-tests. Multivariable logistic regression was used to determine variables independently associated with receiving a patient reminder.ResultsApproximately 22% of children had a parent or guardian report receiving a patient reminder for influenza vaccination for their child, ranging from 12.9% in Idaho to 41.2% in Mississippi. Children with a patient reminder were more likely to be vaccinated compared with children without a patient reminder (73.7% versus 55.5%). In the multivariable model, reminder receipt was higher for children 6–23 months compared with children 13–17 years, black children compared with white children, and children whose parent completed the survey in English compared with children whose parent completed the survey in a language other than English or Spanish.ConclusionsAlthough patient reminders are associated with a higher likelihood of influenza vaccination, nationally, less than one-fourth of children had a parent report receiving one. Despite being based on parental report, with its limitations, this study suggests that increasing the number of parents who receive patient reminders for their children may improve vaccination coverage among children.     

Rotavirus vaccination compliance and completion in a Medicaid infant population

We examined completion and compliance rates of rotavirus (RV) vaccination according to the recommendations of the Advisory Committee on Immunization Practices (ACIP) and the Food and Drug Administration approved Prescribing Information (PI) for Rotarix^® (RV1, GlaxoSmithKline Vaccines) and RotaTeq^® (RV5, Merck and Co.) among infants under one year of age covered by Medicaid programs. Healthcare claims data from state Medicaid programs that constituted the Truven Health MarketScan^® Multi-State Medicaid Database were retrieved from May 2008–June 2012. Infants were grouped under PI and ACIP cohorts based on the dosing regimens followed. The overall compliance per PI (n = 673,956) and ACIP (n = 695,612) recommendations were 24.5% and 28.2%, respectively; completion rates were 30.3% and 32.6%, respectively. In the PI cohort, infants who received RV1 had significantly higher compliance as compared with infants who received RV5 (65.2% vs. 31.3%; p < 0.0001); completion rates among infants receiving RV1 and RV5 were 65.3% and 46.4%, respectively (p < 0.0001). In the ACIP cohort, compliance with RV1 was significantly higher than RV5 (68.8% vs. 45.9%; p < 0.0001) as was the overall completion rate (73.5% vs. 48.8%; p < 0.0001). While compliance is increasing year over year, overall compliance of RV vaccines is suboptimal, with over 40% of eligible infants unvaccinated in both populations. The 2-dose RV vaccine showed better completion rates and higher compliance than the 3-dose RV vaccine in the United States. Public health initiatives focusing on suboptimal compliance and completion rates of RV vaccination in the Medicaid population could improve these metrics, thereby offering protection against RV infection.     

Differential effects of IL-15 on the generation,maintenance and cytotoxic potential of adaptive cellular responses induced by DNA vaccination

IL-15 is an important cytokine for the regulation of lymphocyte homeostasis. However, the role of IL-15 in the generation, maintenance and cytotoxic potential of antigen specific T cells is not fully understood. Because the route of antigenic delivery and the vaccine modality could influence the IL-15 requirement for mounting and preserving cytotoxic T cell responses, we have investigated the immunogenicity of DNA-based vaccines in IL-15 KO mice. DNA vaccination with SIV Gag induced antigen-specific CD4⁺ and CD8⁺ T cells in the absence of IL-15. However, the absolute number of antigen-specific CD8⁺ T cells was decreased in IL-15 KO mice compared to WT animals, suggesting that IL-15 is important for the generation of maximal number of antigen-specific CD8⁺ T cells. Interestingly, antigen-specific memory CD8 cells could be efficiently boosted 8 months after the final vaccination in both WT and KO strains of mice, suggesting that the maintenance of antigen-specific long-term memory T cells induced by DNA vaccination is comparable in the absence and presence of IL-15. Importantly, boosting by DNA 8-months after vaccination revealed severely reduced granzyme B content in CD8⁺ T cells of IL-15 KO mice compared to WT mice. This suggests that the cytotoxic potential of the long-term memory CD8⁺ T cells is impaired. These results suggest that IL-15 is not essential for the generation and maintenance of adaptive cellular responses upon DNA vaccination, but it is critical for the preservation of maximal numbers and for the activity of cytotoxic CD8⁺ T cells.     

A review of recommendations for rotavirus vaccination in Europe: Arguments for change

BackgroundMore than 10 years after the authorisation of two rotavirus vaccines of demonstrated efficacy and with a strongly positive benefit-risk profile, uptake in Europe remains low. Only 13 countries in Europe provide a fully-funded rotavirus universal mass vaccination (UMV) programme, three provide a partially-funded programme, and one provides full funding for a reduced programme targeting at-risk infants. Around 40% of countries in Europe currently have no existing recommendations for rotavirus vaccine use in children from the national government.MethodsWe provide an overview of the status of rotavirus vaccine recommendations across Europe and the factors impeding uptake. We consider the evidence for the benefits and risks of vaccination, and argue that cost-effectiveness and cost-saving benefits justify greater access to rotavirus vaccines for infants living in Europe.ResultsLack of awareness of the direct and indirect burden caused by rotavirus disease, potential cost-saving from rotavirus vaccination including considerable benefits to children, families and society, and government/insurer cost constraints all contribute to complacency at different levels of health policy in individual countries.ConclusionsMore than 10 years after their introduction, available data confirm the benefits and acceptable safety profile of infant rotavirus UMV programmes. Europe serves to gain considerably from rotavirus UMV in terms of reductions in healthcare resource utilization and related costs in both vaccinated subjects and their unvaccinated siblings through herd protection.