Immunogenicity and safety of an E. coli-produced bivalent human papillomavirus (type 16 and 18) vaccine: A randomized controlled phase 2 clinical trial

BackgroundThis study aimed to investigate the dosage, immunogenicity and safety profile of a novel human papillomavirus (HPV) types 16 and 18 bivalent vaccine produced by E. coli.MethodsThis randomized, double-blinded, controlled phase 2 trial enrolled women aged 18–25 years in China. Totally 1600 eligible participants were randomized to receive 90 μg, 60 μg, or 30 μg of the recombinant HPV 16/18 bivalent vaccine or the control hepatitis B vaccine on a 0, 1 and 6 month schedule. The designated doses are the combined micrograms of HPV16 and 18 VLPs with dose ratio of 2:1. The immunogenicity of the vaccines was assessed by measuring anti-HPV 16 and 18 neutralizing antibodies and total IgG antibodies. Safety of the vaccine was assessed.ResultsAll but one of the seronegative participants who received 3 doses of the HPV vaccines seroconverted at month 7 for anti-HPV 16/18 neutralizing antibodies and IgG antibodies. For HPV 16, the geometric mean titers (GMTs) of the neutralizing antibodies were similar between the 60 μg (GMT = 10,548) and 90 μg (GMT = 12,505) HPV vaccine groups and were significantly higher than those in the 30 μg (GMT = 7596) group. For HPV 18, the GMTs of the neutralizing antibodies were similar among the 3 groups. The HPV vaccine was well tolerated. No vaccine-associated serious adverse events were identified.ConclusionThe prokaryotic-expressed HPV vaccine is safe and immunogenic in women aged 18–25 years. The 60 μg dosage formulation was selected for further investigation for efficacy.Clinical trials registration: NCT01356823.     

Immunogenicity and safety of an AS03-adjuvanted H7N1 vaccine in adults 65 years of age and older: A phase II,observer-blind,randomized, controlled trial

BackgroundH7 influenza strains can cause severe and often fatal human infections, especially in the elderly. This phase II, observer-blind, randomized trial (www.ClinicalTrials.gov: NCT01949090) assessed the immunogenicity and safety of a novel AS03-adjuvanted H7N1 vaccine that may serve as a model H7-subtype vaccine.Methods360 adults ≥65 years of age in stable health received either 1 of 4 adjuvanted A/mallard/Netherlands/12/2000 split virion vaccine formulations (3.75 μg or 7.5 μg hemagglutinin adjuvanted with either AS03_A or AS03_B) or saline placebo, given as a 2-dose series. Immunogenicity was assessed using hemagglutination-inhibition (HI) and microneutralization (MN) assays for the per-protocol cohort, comprising 332 participants at 21 days post-each dose, 332 at month 6, and 309 at month 12 (HI assay only). Safety was assessed up to month 12 for all participants who had received ≥1 dose (360 participants).ResultsFor H7N1 HI antibody assessment at day 42 (21 days post-dose 2), seroprotection rates (SPR) in the vaccinated groups were 69.6%–88.7%, seroconversion rates (SCR) 69.6%–88.5%, mean geometric increase (MGI) 11.0–18.9, and HI geometric mean titers (GMTs) 55.0–104.8. These parameters declined by month 6 and month 12. Microneutralization GMTs were 46.2–74.7 in the vaccinated groups at day 42, while vaccine response rate (VRR; proportion with ≥4-fold increase in MN titer) was 46.4%–81.5%. For the cross-reactive H7N9 strain, at day 42, HI GMT were 64.3–201.3, SPR 78.6%–96.3%, SCR 79.3%–96.3%, and MGI 14.1–37.7; MN GMTs were 44.0–85.6, and VRR 46.4–85.2%.The most frequent solicited symptom was injection site pain (41.7%–65.0% of vaccine recipients). In total, 40 participants reported 67 serious adverse events; none were considered causally related to vaccination.ConclusionsIn adults aged ≥65 years, the adjuvanted H7N1 vaccine was immunogenic after 2 doses, and had an acceptable safety profile.www.ClinicalTrials.gov: NCT01949090.     

Safety and immunogenicity of a trivalent recombinant PcpA,PhtD, and PlyD1 pneumococcal protein vaccine in adults,toddlers, and infants: A phase I randomized controlled study

BackgroundPneumococcal protein vaccines (PPrVs) may provide improved protection over currently available polysaccharide and conjugated polysaccharide vaccines. Here, we examined the safety and immunogenicity of a trivalent recombinant PPrV containing PcpA, PhtD, and PlyD1.MethodsThis was a phase I, single-center, randomized, observer-blind study with safety review between cohorts. Adults (18–50 years; n = 30) and then toddlers (12–13 months; n = 30) were randomized 2:1 to receive aluminum-adjuvanted trivalent PPrV (PPrV + adj) containing 50 μg per antigen or placebo. Infants (42–49 days; n = 220) were next randomized to be injected at 6, 10, and 14 weeks of age with 10 μg PPrV + adj or placebo (n = 60; 2:1); 25 μg PPrV + adj, 25 μg unadjuvanted PPrV, or placebo (n = 100; 2:2:1); and 50 μg PPrV + adj or placebo (n = 60; 2:1). Solicited reactions were recorded for 7 days and unsolicited adverse events for 30 days after each vaccination. Concentrations of antibodies to the three vaccine antigens were measured by enzyme-linked immunosorbent assay.ResultsTenderness/pain was the most frequent injection-site reaction. Abnormal crying and irritability (infants), loss of appetite (toddlers), and headache, malaise, and myalgia (adults) were the most frequent systemic reactions. Reactions were mostly mild or moderate, resolved within 3 days, were not adjuvant- or dose-dependent, and were not increased by repeated vaccination. No immediate adverse events, hypersensitivity reactions, or treatment-related serious adverse events were reported. In all PPrV + adj cohorts, at least 75% of subjects had a ≥2-fold increase in all three antibody concentrations. In infants, antibody concentrations were higher with PPrV + adj than with unadjuvanted PPrV, higher with three than two vaccinations, and similar at the different vaccine doses.ConclusionsThe candidate trivalent PPrV was safe and immunogenic in adults, toddlers, and infants. Addition of aluminum adjuvant improved immunogenicity in infants without changing the safety profile.     

Immunogenicity and safety of an AS03-adjuvanted H5N1 pandemic influenza vaccine in Korean adults: A phase IV,randomized, open-label,controlled study

BackgroundAS03-adjuvanted H5N1 pandemic influenza vaccines have been assessed in an extensive clinical development program conducted in North America, Europe, and Asia including children from 6 months of age, adults, and elderly adults. We evaluated AS03-H5N1 in Korean adults 18 through 60 years of age.MethodsThis Phase IV, randomized, study was conducted to assess the immunogenicity, reactogenicity, and safety of two doses (3.75 μg of hemagglutinin antigen) of A/Indonesia/5/2005 (H5N1) adjuvanted with AS03 given 21 days apart in Korean adults. Antibody responses were assessed using hemagglutination-inhibition (HI) assays against the vaccine strain and a vaccine-heterologous strain (A/Vietnam/1194/2004) 21 days after the second dose. A control group (safety) received a licensed seasonal inactivated trivalent influenza vaccine (TIV). Reactogenicity was assessed for 7 days after each vaccination, and unsolicited adverse events were assessed for 182 days following vaccination in both study groups (NCT01730378).ResultsAS03-H5N1 was immunogenic and elicited robust HI antibody responses with seroconversion rates of 100% for the vaccine strain and 69.1% for the heterologous strain (N = 81). HI antibody responses fulfilled the European licensure criteria for immunogenicity (primary endpoint). The incidence of local and systemic solicited adverse events (reactogenicity) was higher with AS03-H5N1 than TIV. There was no apparent difference in the rate of unsolicited adverse events in the AS03-H5N1 and TIV groups.ConclusionThe results indicate that AS03-H5N1 vaccine is immunogenic with reactogenicity and safety findings that are consistent with the established profile of AS03-H5N1 vaccine.     

Adolescent confidence in immunisation: Assessing and comparing attitudes of adolescents and adults

IntroductionThere is limited knowledge of adolescent views and attitudes towards immunisation. Our study investigated adolescent attitudes to immunisation and compared differences in vaccination attitudes between adolescents and adults.MethodsThis study was a cross-sectional, national online survey. Recruitment was stratified by state and gender to ensure findings were nationally representative. Regression analyses were performed to assess and compare adolescent and adult views on vaccine benefits, community protection, risks, side effects, sources of information, and decision-making preference.ResultsIn 2013, 502 adolescents and 2003 adults completed the online survey. Lower levels of vaccine confidence were observed in adolescents with adolescents less likely to believe vaccines are beneficial and/or safe compared to adults (p = 0.043). Compared to females, males were less confident of vaccine benefits (p < 0.05) but less concern about vaccine side effects (p < 0.05). Adolescents were more concerned about vaccine side effects than adults for pain (p < 0.001), redness or swelling (p < 0.001), and fever (p = 0.006). Adolescents were less likely than adults to consider health professionals (p < 0.001) and the media (e.g. internet) (p = 0.010) as important sources of information, and were more likely to seek information from social networks (p < 0.001) including families and schools. Although 62.0% of adolescents agreed that parents should make the decision about vaccination for them, adolescents were more likely to prefer a joint decision with parents (p < 0.001) or by themselves (p = 0.007) compared with adults.ConclusionAdolescents have a lesser understanding of vaccine safety and benefits than adults and have higher concerns about potential vaccine reactions. Improving adolescent awareness and knowledge of the benefits and risks of vaccination through school-based educational programs may improve confidence in and uptake of vaccines for adolescents and increase vaccine confidence in the next generation of parents.     

Immunogenicity and safety of a tetravalent E. coli O-antigen bioconjugate vaccine in animal models

BackgroundExtra-intestinal pathogenic Escherichia coli (ExPEC) are major human pathogens; however, no protective vaccine is currently available. We assessed in animal models the immunogenicity and safety of a 4-valent E. coli conjugate vaccine (ExPEC-4V, serotypes O1, O2, O6 and O25 conjugated to Exotoxin A from Pseudomonas aeruginosa (EPA)) produced using a novel in vivo bioconjugation method.MethodsThree doses of ExPEC-4V (with or without aluminum hydroxide) were administered to rabbits (2 μg or 20 μg per O-antigen, subcutaneously), mice (0.2 μg or 2 μg per O-antigen, subcutaneously) and rats (0.4 μg or 4 μg per O-antigen, intramuscularly). Antibody persistence and boostability were evaluated in rats using O6-EPA monovalent conjugate (0.4 μg O-antigen/dose, intramuscularly). Toxicity was assessed in rats (16 μg total polysaccharide, intramuscularly). Serum IgG and IgM antibodies were measured by ELISA.ResultsRobust antigen-specific IgG responses were observed in all animal models, with increased responses in rabbits when administered with adjuvant. O antigen-specific antibody responses persisted up to 168 days post-priming. Booster immunization induced a rapid recall response. Toxicity of ExPEC-4V when administered to rats was considered to be at the no observed adverse effect level.ConclusionsExPEC-4V conjugate vaccine showed good immunogenicity and tolerability in animal models supporting progression to clinical evaluation.     

Evaluation of anthrax vaccine safety in 18 to 20 year olds: A first step towards age de-escalation studies in adolescents

Background/objectivesAnthrax vaccine adsorbed (AVA, BioThrax^®) is recommended for post-exposure prophylaxis administration for the US population in response to large-scale Bacillus anthracis spore exposure. However, no information exists on AVA use in children and ethical barriers exist to performing pre-event pediatric AVA studies. A Presidential Ethics Commission proposed a potential pathway for such studies utilizing an age de-escalation process comparing safety and immunogenicity data from 18 to 20 year-olds to older adults and if acceptable proceeding to evaluations in younger adolescents. We conducted exploratory summary re-analyses of existing databases from 18 to 20 year-olds (n = 74) compared to adults aged 21 to 29 years (n = 243) who participated in four previous US government funded AVA studies.MethodsData extracted from studies included elicited local injection-site and systemic adverse events (AEs) following AVA doses given subcutaneously at 0, 2, and 4 weeks. Additionally, proportions of subjects with ≥4-fold antibody rises from baseline to post-second and post-third AVA doses (seroresponse) were obtained.ResultsRates of any elicited local AEs were not significantly different between younger and older age groups for local events (79.2% vs. 83.8%, P = 0.120) or systemic events (45.4% vs. 50.5%, P = 0.188). Robust and similar proportions of seroresponses to vaccination were observed in both age groups.ConclusionsAVA was safe and immunogenic in 18 to 20 year-olds compared to 21 to 29 year-olds. These results provide initial information to anthrax and pediatric specialists if AVA studies in adolescents are required.     

A randomized clinical trial in adults and newborns in South Africa to compare the safety and immunogenicity of bacille Calmette-Guérin (BCG) vaccine administration via a disposable-syringe jet injector to conventional technique with needle and syringe

IntroductionIntradermal bacille Calmette-Guérin (BCG) vaccination by needle-free, disposable-syringe jet injectors (DSJI) is an alternative to the Mantoux method using needle and syringe (NS). We compared the safety and immunogenicity of BCG administration via the DSJI and NS techniques in adults and newborn infants at the South African Tuberculosis Vaccine Initiative (SATVI) research site in South Africa.MethodThirty adults and 66 newborn infants were randomized 1:1 to receive intradermal BCG vaccine (0.1 mL in adults; 0.05 mL in infants) via DSJI or NS. Wheal diameter (mm) and skin fluid deposition at the site of injection (SOI) were measured immediately post-vaccination. Adverse events and SOI reactogenicity data were collected 30 min and 1, 2, 4, and 12 weeks after vaccination for adults and at 30 min and 4, 10, and 14 weeks for infants. Blood was collected in infants at 10 and 14 weeks to assess BCG-specific T-cell immune responses.ResultsMore infant BCG vaccinations by DSJI deposited >5 μL fluid on the skin surface, compared to NS (49% versus 9%, p = 0.001). However, all 12 infant vaccinations that did not produce any SOI wheal occurred in the NS group (36%, p < 0.001). Median wheal diameter, in participants for which an SOI wheal formed, did not differ significantly between groups in infants (combined 3.0 mm IQR 2.0 to 4.0, p = 0.59) or in adults (combined 9.0 mm IQR 7.0 to 10.0, p = 0.13). Adverse events were similar between study arms. Proportion of participants with BCG scars after three months did not differ in adults (combined 97%, p = 0.67) or infants (combined 62%, p = 0.13). Frequencies of BCG-specific clusters of differentiation 4 (CD4) and clusters of differentiation 8 (CD8) T-cells co-expressing IFN-γ, TNF-α, IL-2, and/or IL-17 were not different in the DSJI and NS groups.ConclusionBCG vaccination of newborn infants via DSJI was more likely to deliver an appropriate intradermal wheal at the SOI as compared to NS, despite leaving more fluid on the surface of the skin. Safety, reactogenicity, and antigen-specific T-cell immune responses did not differ between DSJI and NS techniques.     

Decennial administration in young adults of a reduced-antigen content diphtheria,tetanus, acellular pertussis vaccine containing two different concentrations of aluminium

BackgroundRegular booster vaccination might be necessary throughout life to protect against pertussis infection. Nevertheless the duration of protection after booster vaccination remains unclear. In this study, antibody persistence up to 10 years after previous vaccination of adolescents (N = 478) with combined reduced-antigen-content diphtheria-tetanus-acellular pertussis vaccine (dTpa, Boostrix™, GlaxoSmithKline Belgium) containing 0.5 mg, 0.3 mg or 0.133 mg of aluminium was assessed. The immunogenicity, reactogenicity and safety of a decennial booster dTpa dose were also investigated.MethodsYoung adults vaccinated as adolescents in the initial booster study were invited to participate in an assessment of antibody persistence at years 8.5 and 10, and to receive a dTpa booster dose at year 10 with immunogenicity assessment one month later. Those who originally received the 0.5 mg or 0.3 mg formulations received the same vaccine at year 10. Those in the 0.133 mg group received the 0.5 mg formulation. Reactogenicity and safety endpoints were captured until 30 days after booster vaccination.ResultsPrior to the decennial booster at year 8.5 and year 10, all participants had seroprotective antibodies for diphtheria (ELISA or neutralisation assay) and tetanus. At least 77.8% were seropositive for anti-pertussis toxin (PT) antibodies at year 8.5 and 82.8% at year 10. All participants were seropositive for antibodies for filamentous haemagglutinin and pertactin at both time points. The decennial booster dose induced robust increases in antibody GMCs to all antigens. The post-booster anti-PT geometric mean concentration was 82.5 EL.U/ml (95%CI 67.0–101.6) and 124.0 (103.5–148.5) in the 0.3 mg and 0.5 mg groups, respectively. The reactogenicity and safety profile of the decennial booster dose was consistent with the known safety profile of dTpa. No serious adverse events were reported.ConclusionsDecennial booster vaccination with either of the two licensed formulations of dTpa was highly immunogenic and well tolerated in young adults. Either formulation could be confidently used as a decennial booster.This study is registered at www.clinicaltrials.gov NCT01147900     

An accelerated rabies vaccine schedule based on toll-like receptor 3 (TLR3) agonist PIKA adjuvant augments rabies virus specific antibody and T cell response in healthy adult volunteers

BackgroundRabies is a fatal disease where post-exposure prophylaxis (PEP) is crucial in preventing infection. However, deaths even after appropriate PEP, have been reported. The PIKA Rabies vaccine adjuvant is a TLR3 agonist that activates B and T cells leading to a robust immune response.MethodsWe conducted a phase I, open label, randomized study in healthy adults to assess the safety and immunogenicity of the PIKA Rabies vaccine and an accelerated vaccine regimen. Thirty-seven subjects were randomized into 3 groups: control vaccine classic regimen, PIKA vaccine classic regimen and PIKA vaccine accelerated regimen. Subjects were followed up for safety, rabies virus neutralizing antibodies (RVNA) and T cell responses.ResultsBoth the control and PIKA Rabies vaccine were well tolerated. All adverse events (AEs) were mild and self-limiting. Seventy-five percent of subjects in the PIKA accelerated regimen achieved a RVNA titer ⩾0.5 IU/mL on day 7, compared to 53.9% in the PIKA classic regimen (p = 0.411) and 16.7% in control vaccine classic regimen (p = 0.012). The PIKA rabies vaccine elicited multi-specific rabies CD4 mediated T cell response already detectable ex vivo at day 7 after vaccination and that was maintained at day 42.ConclusionThe investigational PIKA rabies vaccine was well tolerated and more immunogenic than the commercially available vaccine in healthy adults.Clinical trial registry: The study was registered with clinicaltrials.gov NCT02657161.     

Rabies vaccine preserved by vaporization is thermostable and immunogenic

A rabies vaccine that is thermostable over a range of ambient environmental temperatures would be highly advantageous, especially for tropical regions with challenging cold-chain storage where canine rabies remains enzootic resulting in preventable human mortality. Live attenuated rabies virus (RABV) strain ERAG333 (R333E) was preserved by vaporization (PBV) in a dry, stable foam. RABV stabilized using this process remains viable for at least 23 months at 22 °C, 15 months at 37 °C, and 3 h at 80 °C. An antigen capture assay revealed RABV PBV inactivated by irradiation contained similar levels of antigen as a commercial vaccine. Viability and antigen capture testing confirmed that the PBV process stabilized RABV with no significant loss in titer or antigen content. Live attenuated and inactivated RABV PBV both effectively induced RABV neutralizing antibodies and protected mice from peripheral RABV challenge. These results demonstrate that PBV is an efficient method for RABV stabilization.     

Pneumococcal carriage among children after four years of routine 10-valent pneumococcal conjugate vaccine use in Brazil: The emergence of multidrug resistant serotype 6C

BackgroundIn 2010, the 10-valent pneumococcal conjugate vaccine (PCV10) was introduced free of charge in Brazil as part of the public immunization program. Here we investigated the carriage prevalence, colonization risk factors, capsular types, and antimicrobial resistance among pneumococcal isolates obtained from children in Brazil four years after routine PCV10 use.MethodsBetween September and December 2014, we conducted a cross-sectional study among children < 6 years old who attended one public and two private clinics in Niterói, RJ, Brazil to evaluate pneumococcal nasopharyngeal carriage. Antimicrobial susceptibility and capsular types were determined for all isolates.ResultsOf 522 children, 118 (22.6%) were pneumococcal carriers. Being ≥ 2 years old, attending childcare center, presenting with any symptoms, having acute or chronic respiratory disease, and residing in a slum were associated with pneumococcal carriage. The most prevalent capsular types were 6C (14.5%), 15B/C (11.5%), 11A/D (9.2%), and 6A (7.6%). PCV10 serotypes represented 2.5%. All isolates were susceptible to levofloxacin, rifampicin, and vancomycin. Penicillin non-susceptible pneumococci (PNSP) comprised 39%, with penicillin and ceftriaxone MICs ranging from 0.12–8.0 μg/ml and 0.012–1.0 μg/ml, respectively. The 33 (28%) erythromycin-resistant isolates (MICs of 1.5 to >256 μg/ml) displayed the cMLS_B (72.7%) or M (27.3%) phenotypes, harboring the erm(B) and/or mef(A/E) genes. High non-susceptibility rates (>20%) to clindamycin, erythromycin, penicillin, and tetracycline were largely explained by the prevalence of multidrug resistant (MDR) serotype 6C isolates.ConclusionsEffects of universal childhood PCV10 use on carriage were evident, with the near elimination of PCV10 serotypes. The emergence of MDR serotype 6C isolates, however, is a concern. Ongoing surveillance to monitor serotype 6C increase in invasive diseases is warranted.     

Immunogenicity and safety of a quadrivalent inactivated influenza vaccine compared with two trivalent inactivated influenza vaccines containing alternate B strains in adults: A phase 3, randomized noninferiority study

BackgroundVaccination is the most effective means of influenza prevention. Efficacy of trivalent vaccines may be enhanced by including both B strain lineages. This phase 3, double-blind study assessed the immunogenicity and safety/tolerability of a quadrivalent inactivated influenza vaccine (IIV4) versus the United States (US)-licensed 2014–2015 trivalent inactivated influenza vaccine (IIV3-Yamagata [IIV3-YAM]; Afluria) and IIV3 containing the alternate Victoria B strain (IIV3-VIC) in adults ≥18 years.MethodsParticipants (n = 3484) were randomized 2:1:1 and stratified by age to receive IIV4 (n = 1741), IIV3-YAM (n = 871), or IIV3-VIC (n = 872). The primary objective was to demonstrate noninferiority of the immunological response to IIV4 versus IIV3-YAM and IIV3-VIC. Noninferiority was assessed by hemagglutination inhibition geometric mean titer (GMT) ratio (IIV3/IIV4; upper bound of two-sided 95% confidence interval [CI] ≤ 1.5) and seroconversion rate (SCR) difference (IIV3 – IIV4; upper bound of two-sided 95% CI ≤ 10%) for vaccine strains. Solicited local and systemic adverse events (AEs) were assessed for 7 days postvaccination, AEs recorded for 28 days postvaccination, and serious AEs for 6 months postvaccination.ResultsIIV4 elicited a noninferior immune response for matched strains, and superior response for unmatched B strains not contained in IIV3 comparators. Adjusted GMT ratios (95% CI) for A/H1N1, A/H3N2, B/YAM, and B/VIC strains were 0.93 (0.88, 0.99), 0.93 (0.88, 0.98), 0.87 (IIV3-YAM; 0.82, 0.93), and 0.95 (IIV3-VIC; 0.88, 1.03), respectively. Corresponding values for SCR differences (95% CI) were −1.1 (−4.5, 2.3), −1.7 (−5.0, 1.7), −3.2 (IIV3-YAM; −7.4, 0.9), and −1.6 (IIV3-VIC; −5.8, 2.5). AEs were generally mild and experienced by 52.9% of participants. Serious AEs were reported with a slightly higher frequency with IIV4 (2.3%) versus IIV3-YAM (1.6%) and IIV3-VIC (1.5%).ConclusionsIIV4 demonstrated immunological noninferiority to the US-licensed IIV3, and superiority for unmatched B strains not contained in IIV3 comparators. Safety/tolerability profiles were similar across vaccine groups.Funding: Seqirus; Clinicaltrials.gov: NCT02214225.     

Perfluoroalkyl acids in children and their mothers: Association with drinking water and time trends of inner exposures—Results of the Duisburg birth cohort and Bochum cohort studies

BackgroundPerfluoroalkyl acids (PFAAs) are widely distributed in the environment and humans are globally exposed with them. Contaminated drinking water can considerably contribute to the inner exposure levels.ObjectivesWe report the results of a human biomonitoring study with mother–child pairs living in two German cities, one city with PFAA contaminated drinking water in the sub μg/l-range (Bochum) and the other one without contamination (Duisburg). Furthermore, we studied time trends of exposure levels within the Duisburg cohort study.MethodsWe measured seven PFAAs (PFOS, PFOA, PFHxS, PFNA, PFBS, PFDeA, PFDoA) in blood samples by high performance liquid chromatography and tandem mass spectrometry. Samples were taken during pregnancy, from umbilical cord blood (2000–2002), 6–7 years (5th follow-up) and 8–10 years after birth (7th follow-up). The consumption of drinking water was recorded by a standardized questionnaire. Statistical analyses were calculated with multiple linear regression models.ResultsChildren and mothers from Bochum showed higher PFOS and PFOA plasma concentrations than from Duisburg. The median concentrations (μg/l) for children were: PFOS 4.7 vs. 3.3; PFOA 6.0 vs. 3.6 μg/l (p ≤ 0.05). Consumption of >0.7 l (children) and >0.9 l (mothers) drinking water/day was associated with 13–18% higher PFOS, PFOA and PFHxS concentrations in children (p ≤ 0.01), and 22% higher PFOA in mothers (p ≤ 0.05). Within the Duisburg cohort, PFAA levels in children peaked in the 5th follow-up study (medians (μg/l): cord plasma: 2.7 (PFOS); 1.9 (PFOA); 5th follow-up: 3.6 (PFOS); 4.6 (PFOA); 7th follow-up: 3.3 (PFOS); 3.6 (PFOA)). PFOS concentrations in mothers declined from pregnancy to the 5th follow-up (medians: 8.7 vs. 4.0 μg/l).ConclusionResidents exposed to PFOS and PFOA through drinking water showed significantly higher PFOS and PFOA concentrations in blood plasma. Although PFAA concentrations in the children slightly decreased from the 5th to the 7th follow-up, we detected increasing exposure trends with increasing age in the 7th follow-up.     

Associations between short-term exposure to particulate matter and ultrafine particles and myocardial infarction in Augsburg,Germany

BackgroundShort-term exposure to increased particulate matter (PM) concentration has been reported to trigger myocardial infarction (MI). However, the association with ultrafine particles remains unclear.ObjectivesWe aimed to assess the effects of short-term air pollution and especially ultrafine particles on registry-based MI events and coronary deaths in the area of Augsburg, Germany.MethodsBetween 1995 and 2009, the MONICA/KORA myocardial infarction registry recorded 15,417 cases of MI and coronary deaths. Concentrations of PM < 10 μm (PM₁₀), PM < 2.5 μm (PM_2.5), particle number concentration (PNC) as indicator for ultrafine particles, and meteorological parameters were measured in the study region. Quasi-Poisson regression adjusting for time trend, temperature, season, and weekday was used to estimate immediate, delayed and cumulative effects of air pollutants on the occurrence of MI. The daily numbers of total MI, nonfatal and fatal events as well as incident and recurrent events were analysed.ResultsWe observed a 1.3% risk increase (95%-confidence interval: [−0.9%; 3.6%]) for all events and a 4.4% [−0.4%; 9.4%] risk increase for recurrent events per 24.3 μg/m³ increase in same day PM₁₀ concentrations. Nonfatal events indicated a risk increase of 3.1% [−0.1%; 6.5%] with previous day PM₁₀. No association was seen for PM_2.5 which was only available from 1999 on. PNC showed a risk increase of 6.0% [0.6%; 11.7%] for recurrent events per 5529 particles/cm³ increase in 5-day average PNC.ConclusionsOur results suggested an association between short-term PM₁₀ concentration and numbers of MI, especially for nonfatal and recurrent events. For ultrafine particles, risk increases were notably high for recurrent events. Thus, persons who already suffered a MI seemed to be more susceptible to air pollution.     

The free vaccination policy of influenza in Beijing,China: The vaccine coverage and its associated factors

BackgroundIn order to improve influenza vaccination coverage, the coverage rate and reasons for non-vaccination need to be determined. In 2007, the Beijing Government published a policy providing free influenza vaccinations to elderly people living in Beijing who are older than 60. This study examines the vaccination coverage after the policy was carried out and factors influencing vaccination among the elderly in Beijing.MethodsA cross-sectional survey was conducted through the use of questionnaires in 2013. A total of 1673 eligible participants were selected by multistage stratified random sampling in Beijing using anonymous questionnaires in-person. They were surveyed to determine vaccination status and social demographic information.ResultsThe influenza vaccination coverage was 38.7% among elderly people in Beijing in 2012. The most common reason for not being vaccinated was people thinking they did not need to have a flu shot. After controlling for age, gender, income, self-reported health status, and the acceptance of health promotion, the rate in rural areas was 2.566 (95% confidence interval [CI], 1.801–3.655, P < 0.010) times greater than that in urban areas. Different mechanisms of health education and health promotion have different influences on vaccination uptake. Those whom received information through television, community boards, or doctors were more likely to get vaccinated compared to those who did not (Odds Ratio [OR] = 1.403, P < 0.010; OR = 1.812, P < 0.010; OR = 2.647, P < 0.010).ConclusionThe influenza vaccine coverage in Beijing is much lower than that of developed countries with similar policies. The rural–urban disparity in coverage rate (64.1% versus 33.5%), may be explained by differing health provision systems and personal attitudes toward free services due to socioeconomic factors. Methods for increasing vaccination levels include increasing the focus on primary care and health education programs, particularly recommendations from doctors, to the distinct target populations, especially with a focus on expanding these efforts in urban areas.     

Waning vaccine protection against influenza A (H3N2) illness in children and older adults during a single season

BackgroundRecent studies have suggested that vaccine-induced protection against influenza may decline within one season. We reanalyzed data from a study of influenza vaccine effectiveness to determine if time since vaccination was an independent predictor of influenza A (H3N2).MethodsPatients with acute respiratory illness were actively recruited during the 2007–2008 season. Respiratory swabs were tested for influenza, and vaccination dates were determined by a validated immunization registry. The association between influenza RT-PCR result and vaccination interval (days) was examined using multivariable logistic regression, adjusting for calendar time, age and other confounders.ResultsThere were 629 vaccinated participants, including 177 influenza A (H3N2) cases and 452 test negative controls. The mean (SD) interval from vaccination to illness onset was 101.7 (25.9) days for influenza cases and 93.0 (29.9) days for controls. There was a significant association between vaccination interval and influenza result in the main effects model. The adjusted odds ratio (aOR) for influenza was 1.12 (CI 1.01, 1.26) for every 14 day increase in the vaccination interval. Age modified the association between vaccination interval and influenza (p = 0.005 for interaction). Influenza was associated with increasing vaccination interval in young children and older adults, but not in adolescents or non-elderly adults. Similar results were found when calendar week of vaccine receipt was assessed as the primary exposure variable.ConclusionsIdentification of influenza A (H3N2) was associated with increasing time since vaccination among young children and older adults during a single influenza season.     

Effect of change in sequence of administration of DTwP and Hepatitis B vaccines on perception of pain in infants: A randomized control trial

ObjectiveThis study was designed with objective to study pain response of infants to change in sequence of administration of Hepatitis B and DTwP vaccines.MethodsThis was a randomized parallel control trial. The study was carried out in the immunization clinic of the Department of Pediatrics, LLRM Medical College, Meerut. One hundred and thirty healthy term infants up to 4 months of age were injected either DTwP vaccine first or Hepatitis B vaccine first, followed one minute later by the other vaccine.ResultBaseline characteristics did not differ between the groups. The mean (SD) of AUC of MFCS and NIPS was significantly more in DF group as compared to HF group (for MFCS 25.5 ± 5.4 versus 22.5 ± 5.5, p < 0.01; for NIPS 31.77 ± 5.5 versus 27.64 ± 6.9, p < 0.01). Similarly mean (SD) of AUC of Heart rate and saturation of oxygen showed significant variation in DF group as compared to HF group (for heart rate 591.6 ± 55 versus 559.6 ± 49, p < 0.01; for SpO₂ 326.4 ± 12 versus 335 ± 8, p < 0.01).ConclusionThese results showed that infant experienced lesser pain when Hepatitis B was administered first than when DTwP vaccine was given first.     

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.