Folic acid supplementation in pregnant women with hepatitis B surface antigen improves infant hepatitis B surface antibody mediated by infant IL-4.

Immunoprophylaxis has not completely eliminated hepatitis B virus (HBV) infection due to hyporesponsiveness to hepatitis B vaccine (HepB). We explored the impact of folic acid supplementation (FAS) in pregnant women with positive hepatitis B surface antigen (HBsAg) on their infant hepatitis B surface antibody (anti-HBs) and the mediation effect of infant interleukin-4 (IL-4). We recruited HBsAg-positive mothers and their neonates at baseline. Maternal FAS was obtained via a questionnaire, and neonatal anti-HBs and IL-4 were detected. Follow-up was performed at 11-13 months of age of infants, when anti-HBs and IL-4 were measured. We applied univariate and multivariate analyses. A mediation effect model was performed to explore the mediating role of IL-4. A total of 399 mother-neonate pairs were enrolled and 195 mother-infant pairs were eligible for this analysis. The infant anti-HBs geometric mean concentrations in the maternal FAS group were significnatly higher than those in the no-FAS group (383·8 mIU/ml, 95 % CI: 294·2 mIU/ml to 500·7 mIU/ml v. 217·0 mIU/ml, 95 % CI: 147·0 mIU/ml to 320·4 mIU/ml, z = -3·2, P = 0·001). Infants born to women who took folic acid (FA) within the first trimester were more likely to have high anti-HBs titres (adjusted ß-value = 194·1, P = 0·003). The fold change in IL-4 from neonates to infants partially mediated the beneficial influence of maternal FAS on infant anti-HBs (24·7 % mediation effect) after adjusting for confounding factors. FAS during the first trimester to HBsAg-positive mothers could facilitate higher anti-HBs levels in infants aged 11-13 months partly by upregulating IL-4 in infants.

Montanide ISA-720 and Naloxone in HBsAg Vaccine Formulation: Cytokine Profiling and Monitoring of Long-Lasting Humoral Immune Responses.

Objective: This study aimed to investigate the effects of Montanide ISA-720 and Naloxone (NLX) in Hepatitis B surface antigen (HBsAg) vaccine formulation on cytokine and long-lasting antibody responses. Methods: First, the HBsAg was formulated in Montanide ISA-720 adjuvant and Naloxone at 5 and 10 mg/kg. The experimental mice were immunized three times at a 2-week interval, and then IL-4, IL-2, TNF-α, and IFN-γ cytokines; long-lasting IgG antibody responses 220 days after the last shot; and IgG1/IgG2a isotypes were assessed by ELISA. Results: The HBsAg-Alum group exhibited the highest IL-4 cytokine response among the experimental groups, whereas NLX in HBsAg-MON720 vaccine formulation did not affect cytokine responses. In addition, NLX in Alum-based vaccine suppressed IL-4 cytokine response and increased the IL-2/IL-4 cytokine ratio. Moreover, HBsAg-MON720 was more potent than HBsAg-Alum in the induction of antibody responses, and NLX in Alum- and MON720-based vaccines induced long-lasting antibody responses. Conclusion: NLX in Alum-based vaccine decreased IL-4 cytokine response, increased IL-2/IL-4 cytokine ratio, and improved long-lasting humoral immune responses in both vaccine formulations. Therefore, the adjuvant activity of NLX in the vaccine formulation depends on the type of adjuvant and the nature of the antigen in the vaccine formulation.

Association of hepatitis B vaccine response to vitamin D supplementation and ultraviolet B (UVB) exposure during different time intervals in experimental animals.

The implications of vitamin D deficiency on the immune system have become clearer in recent years, being associated with less immune response following HBV vaccine. We aimed to elucidate the effect of vitamin D supplementation and UVB exposure on short- and long-term performance of hepatitis B vaccine. Forty-five male rabbits were randomly divided into 3 groups that were immunized with recombinant HBsAg. The first group (group I) represented a negative control group, whereas group III rabbits were administered with commercially available 1,25 (OH)2 vitamin D as an alternative for UVB exposure in group II. Results showed that vitamin D concentrations were significantly higher in UVB exposed group compared to both negative control and vitamin D-supplemented groups during short- and long-time intervals. In addition, means of anti-HBsAg isotypes' levels and anti-HBsAg IgG avidity% were significantly higher in negative control group compared to other groups during short- and long-time intervals. Moreover, vitamin D serum concentration was positively correlated with anti-HBsAg IgG level and avidity % in both negative control and vitamin D-supplemented groups, while it was negatively correlated with anti-HBsAg IgM level in negative control group. It can be concluded from the above results that UVB radiation may have both augmenting and suppressive effects and that circulating serum vitamin D concentration may have a positive association with premium immune modulation following HBV vaccination.

Association Between 2-Dose vs 3-Dose Hepatitis B Vaccine and Acute Myocardial Infarction.

Importance: The 2-dose hepatitis B vaccine with a cytosine phosphoguanine adjuvant (HepB-CpG vaccine; Heplisav-B) generated higher seroprotection in prelicensure trials than did a 3-dose hepatitis B vaccine with an aluminum hydroxide adjuvant (HepB-alum vaccine; Engerix-B). However, in 1 trial, a higher number of acute myocardial infarction (MI) events were observed among those who received the HepB-CpG vaccine than among those who received the HepB-alum vaccine, an outcome requiring further study. Objective: To compare the rate of acute MI between recipients of HepB-CpG vaccine and HepB-alum vaccine. Design, Setting, and Participants: This prospective cohort noninferiority study was conducted at Kaiser Permanente Southern California (KPSC), an integrated health care system with 15 medical centers and approximately 4.7 million members. The study included 69 625 adults not undergoing dialysis who received at least 1 dose of a hepatitis B vaccine in either family medicine or internal medicine departments at KPSC from August 7, 2018, to October 31, 2019 (November 30, 2020, final follow-up). Exposures: Receipt of HepB-CpG vaccine vs HepB-alum vaccine. The first dose during the study period was the index dose. Main Outcomes and Measures: Individuals were followed up for 13 months after the index dose for occurrence of type 1 acute MI. Potential events were identified using diagnosis codes and adjudicated by cardiologists. The adjusted hazard ratio (HR) of acute MI was estimated comparing recipients of HepB-CpG vaccine with recipients of HepB-alum vaccine, with inverse probability of treatment weighting (IPTW) to adjust for demographic and clinical characteristics. The upper limit of the 1-sided 97.5% CI was compared with a noninferiority margin of 2. Results: Of the 31 183 recipients of HepB-CpG vaccine (median age, 49 years; IQR, 38-56 years), 51.2% (n = 15 965) were men, and 52.7% (n = 16 423) were Hispanic. Of the 38 442 recipients of HepB-alum (median age, 49 years; IQR, 39-56 years), 50.8% (19 533) were men, and 47.1% (n = 18 125) were Hispanic. Characteristics were well-balanced between vaccine groups after IPTW. Fifty-two type 1 acute MI events were confirmed among recipients of HepB-CpG vaccine for a rate of 1.67 per 1000-person-years, and 71 type 1 acute MI events were confirmed among recipients of HepB-alum vaccine for a rate of 1.86 per 1000 person-years (absolute rate difference, -0.19 [95% CI, -0.82 to 0.44]; adjusted HR, 0.92 [1-sided 97.5% CI, ∞ to 1.32], which was below the noninferiority margin; P < .001 for noninferiority). Conclusions and Relevance: In this cohort study, receipt of HepB-CpG vaccine compared with HepB-alum vaccine did not meet the statistical criterion for increased risk of acute myocardial infarction.

Determinants and preventive practices of midwives and physicians toward vertical transmission of hepatitis B in Ghana: a cross-sectional survey.

Introduction: countries in sub-Saharan Africa, including Ghana, are disproportionately affected by hepatitis B viral (HBV) infection. In these areas, mother-to-child transmission (MTCT) is an essential mode of HBV transmission. Evidently, timely hepatitis B birth dose vaccination remains an effective preventive intervention against MTCT of HBV. Considering that midwives and physicians are the primary care providers of newborns in Ghana, we sought to examine their preventive practices toward vertical transmission of HBV in the eastern region of Ghana. Methods: a cross-sectional survey was conducted with 126 healthcare providers (HCP; midwives and physicians). The participants were conveniently recruited from one regional hospital and four district hospitals. Statistical significance was set at 0.05 alpha level. Results: the findings indicate that 42.9% (n = 54) of HCPs' prevention of mother to child transmission (PMTCT) practices for hepatitis B were good (X2 = 2.57, p > 0.05). Explicitly, 79% indicated screening all pregnant women for hepatitis B as part of antenatal care (X2 = 41.14, p < 0.001). Additionally, about half of the participants (52.4%) reported providing pre-test counselling (X2 = 0.29, p > 0.05), whereas one-third (33%) reported routinely administering a birth dose of the hepatitis B vaccine to neonates of mothers with hepatitis B (X2 = 14.00, p < 0.001). However, only 37% reported administering the hepatitis B vaccine to newborns within 12 hours of birth (X2 = 9.18, p < 0.01). The binary logistic regression analyses identified training as the only significant predictor of good practice on PMTCT of hepatitis B at the 5% level (Wald = 3.91, p =0.05). Conclusion: given that more than half of the participants in the study area had incorrect PMTCT practices for hepatitis B, it is imperative that a series of workshops on hepatitis B be done for healthcare providers in Ghana. In addition, hepatitis B birth dose vaccine must be incorporated into the ´Expanded Programme on Immunisation´ to remove the cost that acts as a barrier to access.

Improvement of hepatitis B vaccine to induce IFN-γ cytokine response: A new formulation.

Hepatitis B virus (HBV) infection is limited through vaccination against HBsAg formulated in the Alum adjuvant. However, this alum-formulated vaccine fails to be preventive in some cases, also known as non-responders. Recent studies have shown the immunomodulatory effect of α-tocopherol in various models. Here, we developed a new formulation for HBsAg using α-tocopherol, followed by assessment of immune responses. Experimental BALB/c mice were immunized with a commercial alum-based vaccine or the one formulated in α-tocopherol at different doses. Mice were immunized subcutaneously with 5 µg of HBsAg with different formulations three times with 2-week intervals. Specific total IgG, IgG1, and IgG2a isotypes of antibodies were measured by ELISA. Immunologic cytokines, such as IFN-γ, IL-4, IL-2, and TNF-α, were also evaluated through commercial ELISA kits. Our results showed that the new α-tocopherol-formulated vaccine had the ability to reinforce specific total IgG responses. Moreover, α-tocopherol in the HBsAg vaccine increased IFN-γ, IL-2, and TNF-α cytokines at higher concentrations; however, the vaccine suppressed IL-4 cytokine release. At a lower concentration of α-tocopherol, the IL-4 cytokine response increased without a positive effect on IFN-γ and TNF-α cytokine response. It seems that α-tocopherol can change the immune responses against HBsAg; however, the type of response depends on the dose of α-tocopherol used in the vaccine formulation.

Vitamin D and the hepatitis B vaccine response: a prospective cohort study and a randomized, placebo-controlled oral vitamin D3 and simulated sunlight supplementation trial in healthy adults.

PURPOSE: To determine serum 25(OH)D and 1,25(OH)2D relationship with hepatitis B vaccination (study 1). Then, to investigate the effects on hepatitis B vaccination of achieving vitamin D sufficiency (serum 25(OH)D ≥ 50 nmol/L) by a unique comparison of simulated sunlight and oral vitamin D3 supplementation in wintertime (study 2). METHODS: Study 1 involved 447 adults. In study 2, 3 days after the initial hepatitis B vaccination, 119 men received either placebo, simulated sunlight (1.3 × standard-erythema dose, 3 × /week for 4 weeks and then 1 × /week for 8 weeks) or oral vitamin D3 (1000 IU/day for 4 weeks and 400 IU/day for 8 weeks). We measured hepatitis B vaccination efficacy as percentage of responders with anti-hepatitis B surface antigen immunoglobulin G ≥ 10 mIU/mL. RESULTS: In study 1, vaccine response was poorer in persons with low vitamin D status (25(OH)D ≤ 40 vs 41-71 nmol/L mean difference [95% confidence interval] - 15% [- 26, - 3%]; 1,25(OH)2D ≤ 120 vs ≥ 157 pmol/L - 12% [- 24%, - 1%]). Vaccine response was also poorer in winter than summer (- 18% [- 31%, - 3%]), when serum 25(OH)D and 1,25(OH)2D were at seasonal nadirs, and 81% of persons had serum 25(OH)D < 50 nmol/L. In study 2, vitamin D supplementation strategies were similarly effective in achieving vitamin D sufficiency from the winter vitamin D nadir in almost all (~ 95%); however, the supplementation beginning 3 days after the initial vaccination did not effect the vaccine response (vitamin D vs placebo 4% [- 21%, 14%]). CONCLUSION: Low vitamin D status at initial vaccination was associated with poorer hepatitis B vaccine response (study 1); however, vitamin D supplementation commencing 3 days after vaccination (study 2) did not influence the vaccination response. CLINICAL TRIAL REGISTRY NUMBER: Study 1 NCT02416895; https://clinicaltrials.gov/ct2/show/study/NCT02416895 ; Study 2 NCT03132103; https://clinicaltrials.gov/ct2/show/NCT03132103 .

Effect of Bruton tyrosine kinase inhibitor on efficacy of adjuvanted recombinant hepatitis B and zoster vaccines.

Vaccinations are effective in preventing infections; however, it is unknown if patients with chronic lymphocytic leukemia (CLL) who are treatment naïve (TN) or receiving Bruton tyrosine kinase inhibitors (BTKi's) respond to novel adjuvanted vaccines. Understanding the effect of BTKi's on humoral immunity is timely because BTKi's are widely used and vaccination against coronavirus disease 2019 is urgently needed. In 2 open-label, single-arm clinical trials, we measured the effect of BTKi's on de novo immune response against recombinant hepatitis B vaccine (HepB-CpG) and recall response against recombinant zoster vaccine (RZV) in CLL patients who were TN or on BTKi. The primary end point was serologic response to HepB-CpG (anti-hepatitis B surface antibodies ≥10 mIU/mL) and RZV (≥fourfold increase in anti-glycoprotein E). The response rate to HepB-CpG was lower in patients on BTKi (3.8%; 95% confidence interval [CI], 0.7-18.9) than patients who were TN (28.1%; 95% CI, 15.6-45.4; P = .017). In contrast, the response rate to RZV did not differ significantly between the BTKi (41.5%; 95% CI, 27.8-56.6) and TN cohorts (59.1%; 95% CI, 38.7-76.7; P = .2). BTKi's were associated with a decreased de novo immune response following HepB-CpG, whereas recall immune response following RZV was not significantly affected by BTKi therapy. These trials were registered at www.clinicaltrials.gov as #NCT03685708 (Hep-CpG) and #NCT03702231 (RZV).

Association of Number of Doses With Hepatitis B Vaccine Series Completion in US Adults.

Importance: Receipt of hepatitis B virus vaccine is important to prevent infection. However, adherence to the hepatitis B vaccine series among adults at risk of infection has been low. Objective: To assess whether recipients of a 2-dose hepatitis B vaccine with cytosine phosphoguanine adjuvant (HepB-CpG vaccine; Heplisav-B) are more likely to complete their series compared with recipients of a 3-dose vaccine with alum adjuvant (comparator vaccine; Engerix-B [HepB-alum]). Design, Setting, and Participants: This nested cohort study was conducted from August 7 to December 31, 2018, at Kaiser Permanente Southern California, an integrated health care system with a diverse population of approximately 4.6 million members. Adults not receiving dialysis who received a first dose of a hepatitis B vaccine series in family practice or internal medicine departments of 15 Kaiser Permanente Southern California medical centers were followed up through electronic health records for up to 1 year after receipt of the first dose. Data were analyzed from March 16 to September 23, 2020. Exposures: Receipt of a first dose of the HepB-CpG vaccine (2-dose vaccine) vs receipt of a first dose of the HepB-alum vaccine (3-dose vaccine). Main Outcomes and Measures: Series completion within the recommended vaccine schedule plus 3 months (primary outcome) and series completion within 1 year after receipt of the first dose (secondary outcome). Results: Of 4727 individuals who initiated the HepB-CpG vaccine series and 6161 individuals who initiated the HepB-alum vaccine series included in the study, 2876 (60.8%) and 3789 (61.5%), respectively, were ages 40 to 59 years, 2415 (51.1%) and 3113 (50.5%) were male, and 2364 (50.0%) and 2881 (46.8%) were Hispanic. The vaccine series was completed within the recommended schedule plus 3 months for 2111 (44.7%) individuals who initiated the HepB-CpG vaccine series and 1607 (26.1%) individuals who initiated the HepB-alum vaccine series, and within 1 year for 2858 (60.5%) and 1989 (32.3%) individuals, respectively. The individuals who initiated the HepB-CpG vaccine series were significantly more likely to complete the series (adjusted relative risk, 1.77; 95% CI, 1.68-1.87). Results were consistent across clinical and demographic strata. Conclusions and Relevance: In this study, use of the HepB-CpG vaccine was associated with hepatitis B vaccine series completion, but tailored strategies to increase completion of hepatitis B vaccine series are warranted.

Dental auxiliary hepatitis B immunization: a cross-sectional study in the São Paulo state public health system, Brazil, 2018. / Imunização contra hepatite B em auxiliares em saúde bucal: estudo transversal no sistema público de saúde do estado de São Paulo, em 2018.

OBJECTIVE: to investigate dental auxiliaries (DA) hepatitis B immunization in Brazilian National Health System (SUS) services in nine cities in São Paulo State, Brazil, in 2018. METHODS: this was a cross-sectional study based on interviews using a questionnaire as well as evaluation of immunity using the anti-HBs test, evaluation of prior testing, test result and interpretation and guidance provided about hepatitis B. RESULTS: of the 70 registered DA, 35 completed the course of vaccinations, 29 had negative anti-HBs test results, 16 had tested previously, and 43 did not correctly understand their result; there was association (p=0.025) between completed course of vaccinations and receipt of guidance. CONCLUSION: most DA received guidance about hepatitis B; however, a considerable portion did not complete the course of vaccinations and had negative anti-HBs test results; few DA had tested previously nor correctly interpreted the result; evidence was found of an alarming scenario in which there are severe shortcomings in DA hepatitis B immunization.

Lipopolysaccharide derived alginate coated Hepatitis B antigen loaded chitosan nanoparticles for oral mucosal immunization.

Mucosal administration of vaccine can produce a strong immune response. Antigens adhere to "M-cells", present at the intestinal mucosa and the M-cells produce immunity after actively transporting luminal antigens to the underlying immune cells. The objective of the present study was to prepare and characterize alginate coated chitosan nanoparticles (ACNPs) loaded with HBsAg as an antigen to produce immunity; additionally anchored with lipopolysaccharide (LPS) as an adjuvant. Ionic gelation method was used to prepare chitosan nanoparticles (CNPs) which were loaded with HBsAg and stabilized by alginate coating to protect from gastric environment. Results showed that the prepared LPS-HB-ACNPs were small and spherical with mean particle size 605.23 nm, polydispersity index 0.234 and Zeta potential -26.2 mV and could effectively protect antigen at GIT in acidic medium. HB-ANCPs were stable during storage at 4 ± 1 and 27 ± 2 °C. Anchoring with LPS showed increased immunity as compared to other formulations. Additionally, NPs elicited significant sIgA at mucosal secretions and IgG antibodies in systemic circulation. Thus, the prepared LPS anchored alginate coated chitosan NPs may be a promising approach as a vaccine delivery system for oral mucosal immunization.

Adjuvant effect of Vernonia amygdalina leaf extract on host immune response to hepatitis B virus subunit vaccine.

Aim of the study: Adjuvants can increase the efficiency and reduce the number of required doses for hepatitis B vaccination. Thus the study was designed to investigate whether V. amygdalina leaf extract may be used as an adjuvant to the conventional hepatitis B surface antigen-based vaccine through humoral response analyses. Methodology: The toxicity/safety margin of V. amygdalina was determined using Lorke's method. Immunization was carried out in mice in two phases, phase 1 employed a 3-times vaccination schedule while phase 2 tested 2-times vaccination schedule. The humoral immune response was determined using ELISA test. The total white blood count, different white blood count, aspartate aminotransferase level, alanine aminotransferase level were determined and the body weight of the mice periodically monitored. Results: Our data show that V. amygdalina was not toxic up to the dose of 5000 mg/kg bodyweight (bw). At a concentration of 250 mg/kg bw as an adjuvant in a three times vaccination schedule, it increased IgM, IgG1 and IgA antibody responses. In a 2-times vaccination schedule, 1000 mg/kg of V. amygdalina as an adjuvant to hepatitis B vaccine was able to elicit effective antibody production (0.174±0.002) significantly (P <0.05) higher than the conventional hepatitis B vaccine group (0.109±0.002) which received 3-times vaccine dose. It equally enhanced innate cell-mediated immune response by increasing total white blood cell, neutrophil and lymphocyte counts. The adjuvant-vaccine combination did not produce side effects as the aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were within the normal ranges. The liver excised from the sacrificed mice at the end of the vaccination series showed no sign of congestion, inflammation or colour change. Periodic mice body weight monitoring showed similar growth pattern between the treatment and control groups. Conclusion: Results obtained suggest that V. amygdalina may serve as an effective adjuvant to hepatitis B virus vaccine.

Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) demonstrates distinct autoimmune and autoinflammatory disease associations according to the adjuvant subtype: Insights from an analysis of 500 cases.

BACKGROUND: We investigated the pattern of reported immune diseases in the international ASIA syndrome registry. METHODS: Data from 500 subjects exposed to adjuvants from the ASIA syndrome international registry were analysed. RESULTS: The patient mean age was 43 ±â€¯17 years and 89% were female. Within the reported immune diseases, 69% were well-defined immune diseases (autoimmune, autoinflammation, and mixed pattern diseases). Among the well-defined immune diseases following the exposure to adjuvants, polygenic autoimmune diseases were significantly higher than autoinflammatory disorders (92.7% vs 5.8%, respectively, p < 0.001). Polygenic autoimmune diseases such as connective tissue diseases were significantly linked to the exposure to HBV vaccine (OR 3.15 [95%CI 1.08-9.23], p = 0.036). Polygenic autoinflammatory diseases were significantly associated with the exposure to influenza vaccination (OR 10.98 [95%CI 3.81-31.67], p < 0.0001). CONCLUSIONS: Immune conditions following vaccination are rare, and among these, polygenic autoimmune diseases represent the vast majority of the well-defined immune diseases reported under the umbrella ASIA syndrome. However, vaccines benefit outweighs their autoimmune side effects.

Hepatitis B seroprevalence in 10-25-year-olds in Mexico - the 2012 national health and nutrition survey (ENSANUT) results.

OBJECTIVES: To estimate hepatitis B virus (HBV) seroprevalence from natural infection or vaccination in 10-25-year-olds in Mexico, using the 2012 National Health and Nutrition Survey (ENSANUT). METHODS: Randomly selected serum samples (1,581) from adolescents and young adults, representative of 38,924,584 Mexicans, were analyzed to detect hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs) and hepatitis B core antibody (anti-HBc). Weighted HBV seroprevalence in the Mexican population and association with sociodemographic variables were calculated. RESULTS: Overall weighted seroprevalence from natural infection (positive for anti-HBs and anti-HBc) was 0.23% (95% confidence interval [95% CI] 0.10-0.52). No HBsAg was detected, indicating no acute or chronic infection. Vaccine-derived immunity (positive ≥ 10.0 mIU/ml for anti-HBs and negative to anti-HBc) was 44.7% (95% CI: 40.2-49.4) overall; lower in persons aged 20-25 years (40.83%) than in persons aged 10-19 years (47.7%). Among the population analyzed, 54.2% (95% CI: 49.6-58.8) were seronegative to HBV (negative for all three markers) and no sociodemographic risk factors were identified. CONCLUSIONS: HBV seroprevalence from natural infection was low. Vaccination-induced immunity was higher among Mexican adolescents than young adults, possibly due to vaccination policies since 1999.

Protamine Nanocapsules for the Development of Thermostable Adjuvanted Nanovaccines.

One of the main challenges in the development of vaccine has been to improve their stability at room temperature and eliminate the limitations associated with the cold chain storage. In this paper, we describe the development and optimization of thermostable nanocarriers consisting of an oily core with immunostimulating activity, containing squalene or α tocopherol surrounded by a protamine shell. The results showed that these nanocapsules can efficiently associate the recombinant hepatitis B surface antigen (rHBsAg) without compromising its antigenicity. Furthermore, the freeze-dried protamine nanocapsules were able to preserve the integrity and bioactivity of the associated antigen upon storage for at least 12 months at room temperature. In vitro studies evidenced the high internalization of the nanocapsules by immunocompetent cells, followed by cytokine secretion and complement activation. In vivo studies showed the capacity of rHBsAg-loaded nanocapsules to elicit protective levels upon intramuscular or intranasal administration to mice. Overall, our data indicate that protamine nanocapsules are an innovative thermostable nanovaccine platform for improved antigen delivery.

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

INTRODUCTION: Hepatitis B virus (HBV) infection acquired during pregnancy can pose a risk to the infant at birth that can lead to significant and lifelong morbidity. Hepatitis B vaccine (HepB) is recommended for anyone at increased risk for contracting HBV infection, including pregnant women. Limited data are available on the safety of HepB administration during pregnancy. OBJECTIVES: To assess the frequency of maternal HepB receipt among pregnant women and evaluate the potential association between maternal vaccination and pre-specified maternal and infant safety outcomes. METHODS: We examined a retrospective cohort of pregnancies in the Vaccine Safety Datalink (VSD) resulting in live birth outcomes from 2004 through 2015. Eligible pregnancies in women aged 12-55 years who were continuously enrolled from 6 months pre-pregnancy to 6 weeks postpartum in VSD integrated health systems were included. We compared pregnancies with HepB exposure to those with other vaccine exposures, and to those with no vaccine exposures. High-risk conditions for contracting HBV infection were identified up to one-year prior to or during the pregnancy using ICD-9 codes. Maternal and fetal adverse events were also evaluated according to maternal HepB exposure status. RESULTS: Among over 650,000 pregnancies in the study period, HepB was administered at a rate of 2.1 per 1000 pregnancies (n = 1399), commonly within the first 5 weeks of pregnancy. Less than 3% of the HepB-exposed group had a high-risk ICD-9 code indicating need for HepB; this was similar to the rate among HepB unvaccinated groups. There were no significant associations between HepB exposure during pregnancy and gestational hypertension, gestational diabetes, pre-eclampsia/eclampsia, cesarean delivery, pre-term delivery, low birthweight or small for gestational age infants. CONCLUSIONS: Most women who received maternal HepB did not have high-risk indications for vaccination. No increased risk for the adverse events that were examined were observed among women who received maternal HepB or their offspring.

Maternal folic acid supplementation and antibody persistence 5 years after hepatitis B vaccination among infants.

BACKGROUND: Maternal exposure to dietary factors during pregnancy may modulate the immunity of offspring by epigenetic programming. But the relationship between intrauterine environment and persistence of protective antibody after hepatitis B vaccination has not been reported. This study was to investigate the 5-year persistence of protective antibody response after primary hepatitis B vaccination, and its relationship with maternal folic acid supplementation. MATERIALS AND METHODS: A total of 1461 children who completed a 3-dose 10 µg recombinant hepatitis B vaccine at birth and did not infect hepatitis B virus were followed up. Logistic regression and mediation analysis was used to explore the relationship between 5-year persistence of protective antibody and maternal nutrition. RESULTS: Of 1403 children who did not revaccinated during the follow-up, 76.1% had protective hepatitis B surface antibody (anti-HBs) levels. Twenty percent of mothers did not take folate during pregnancy. Mediation analysis showed a total effect of folic acid supplementation on good persistence (odds ratio: 1.10, 95% CI: 1.03-1.17, p = 0.0010), a direct effect was 1.07 (95% CI: 1.01-1.13, p = 0.0128) and an indirect effect was 1.03 (95% CI: 1.00-1.06, p = 0.0672); the proportion of good persistence mediated by primary response was 30.3%. CONCLUSION: This study indicated a good protective anti-HBs persistence at year 5 after 10 µg recombination hepatitis B vaccination in infants. Maternal folic acid supplementation may improve the persistence of protective antibodies through other pathways. Multi-center cohort studies should be conducted to verify this conclusion.

Efficacy of Arsenicum album 30cH in preventing febrile episodes following DPT-HepB-Polio vaccination - a randomized, double-blind, placebo-controlled clinical trial.

BACKGROUND: Among the post-immunization adverse events, especially of Diphtheria-Pertusis-Tetanus (DPT), fever is a common systemic reaction. There is anecdotal support for the use of the homeopathic medicine Arsenicum album in preventing post-vaccination fever. The investigators intended to evaluate its efficacy in preventing febrile episodes following vaccination. METHODS: In the community medicine out-patient of Mahesh Bhattacharyya Homoeopathic Medical College and Hospital, West Bengal, India, between August 2014 and January 2017, a double-blind, randomized, placebo-controlled trial was conducted on 120 children (verum: 60, placebo: 60) who presented for the 2nd and 3rd dose of DPT-HepB-Polio vaccination and reported febrile episodes following the 1st dose. Intervention used was Arsenicum album 30cH 6 doses or placebo (indistinguishable from verum), thrice daily for two subsequent days. Parents were advised to report any event of febrile attacks within 48h of vaccination, either directly or over telephone. RESULTS: The groups were comparable at baseline. Children reporting fever after the 2nd dose was 29.8% and 30.4% respectively for the homeopathy group and control group respectively [Relative Risk (RR)=1.008] with no significant difference (P=0.951) between groups. Again after the 3rd dose, children reporting fever were 31.5% and 28.3% respectively for the homeopathy group and control group respectively (RR=0.956) with no significant difference (P=0.719) between groups. CONCLUSION: Empirically selected Arsenicum album 30cH could not produce differentiable effect from placebo in preventing febrile episodes following DPT-HepB-Polio vaccination. [Trial registration: CTRI/2017/02/007939].

Evidence Refuting the Existence of Autoimmune/Autoinflammatory Syndrome Induced by Adjuvants (ASIA).

Autoimmune/autoinflammatory syndrome induced by adjuvants (ASIA) was described in 2011. Over time the condition and its triggers have broadened to include several autoimmune disorders, the macrophagic myofasciitis syndrome, the Gulf war syndrome, the sick building syndrome, siliconosis, and the chronic fatigue syndrome. The aluminum-containing adjuvants in the hepatitis B vaccine and the human papillomavirus vaccine in particular have been stated to be the major causes of the disorder. Here, we review the specificity of the diagnostic criteria for ASIA. We also examine relevant human data, pertaining to causation, particularly from patients undergoing allergen-specific immunotherapy (IT). Patients undergoing allergen-specific IT receive 100 to 500 times more injected aluminum over 3 to 5 years, compared with hepatitis B and human papillomavirus vaccine recipients. In a large pharmacoepidemiological study, in contrast to case series of ASIA, patients receiving aluminum-containing allergen IT preparations were shown to have a lower incidence of autoimmune disease. In another clinical trial, there were no increases in exacerbations in a cohort of patients with systemic lupus erythematosus immunized with the hepatitis B vaccine. Current data do not support the causation of ASIA by vaccine adjuvants containing aluminum, which should be of reassurance to patients undergoing routine immunizations as well as to those undergoing allergen-specific IT.

National, Regional, State, and Selected Local Area Vaccination Coverage Among Adolescents Aged 13-17 Years - United States, 2016.

The Advisory Committee on Immunization Practices (ACIP) recommends that adolescents routinely receive tetanus, diphtheria, and acellular pertussis vaccine (Tdap), meningococcal conjugate vaccine (MenACWY), and human papillomavirus (HPV) vaccine (1) at age 11-12 years. ACIP also recommends catch-up vaccination with hepatitis B vaccine, measles, mumps, and rubella (MMR) vaccine, and varicella vaccine for adolescents who are not up to date with childhood vaccinations. ACIP recommends a booster dose of MenACWY at age 16 years (1). In December 2016, ACIP updated HPV vaccine recommendations to include a 2-dose schedule for immunocompetent adolescents initiating the vaccination series before their 15th birthday (2). To estimate adolescent vaccination coverage in the United States, CDC analyzed data from the 2016 National Immunization Survey-Teen (NIS-Teen) for 20,475 adolescents aged 13-17 years.* During 2015-2016, coverage increased for ≥1 dose of Tdap (from 86.4% to 88.0%) and for each HPV vaccine dose (from 56.1% to 60.4% for ≥1 dose). Among adolescents aged 17 years, coverage with ≥2 doses of MenACWY increased from 33.3% to 39.1%. In 2016, 43.4% of adolescents (49.5% of females; 37.5% of males) were up to date with the HPV vaccination series, applying the updated HPV vaccine recommendations retrospectively.† Coverage with ≥1 HPV vaccine dose varied by metropolitan statistical area (MSA) status and was lowest (50.4%) among adolescents living in non-MSA areas and highest (65.9%) among those living in MSA central cities.§ Adolescent vaccination coverage continues to improve overall; however, substantial opportunities exist to further increase HPV-associated cancer prevention.