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For decades, breast implants have been available for breast reconstructions and breast augmentations to improve the patients' health-related quality of life. Silicone implants (SI) have been used since the middle of the last century for breast reconstruction, for example after breast cancer, for birth defects, gender confirmation procedures, or for breast augmentation. Every year, several hundred SI are performed in Iceland for these purposes, but no central register is maintained. It can be estimated that at least 1000 - 3000 women have SI in Iceland and that around 300 Icelandic patients get SI every year. This informal review article discusses the so-called ASIA syndrome, the immunological effects of silicone and the possible relationship of SI to autoimmune diseases, symptoms, and diagnosis. In the methodology, this paper does not rely on the strict conditions of systematic reviews, but the authors relied only on peer-reviewed sources through PubMed, UpToDate and Scopus. The keywords used are silicon, silicon implant, silicon particles, immune response, autoimmunity, autoinflammation, Autoimmune/inflammatory syndrome induced by aduvants, ASIA, ASIA syndrome, breast implant illness. The paper reviews known facts about the disease, its characteristics, and statistical aspects.

Background: Coexistence of childhood asthma, eczema and allergic rhinitis is higher than can be expected by chance, suggesting a common mechanism. Data on allergic multimorbidity from a pan-European, population-based birth cohort study have been lacking. This study compares the prevalence and early-life risk factors of these diseases in European primary school children., Methods: In the prospective multicentre observational EuroPrevall-iFAAM birth cohort study, we used standardized questionnaires on sociodemographics, medical history, parental allergies and lifestyle, and environmental exposures at birth, 12 and 24 months. At primary school age, parents answered ISAAC-based questions on current asthma, rhinitis and eczema. Allergic multimorbidity was defined as the coexistence of at least two of these., Results: From 10,563 children recruited at birth in 8 study centres, we included data from 5,572 children (mean age 8.2 years; 51.8% boys). Prevalence estimates were as follows: asthma, 8.1%; allergic rhinitis, 13.3%; and eczema, 12.0%. Allergic multimorbidity was seen in 7.0% of the whole cohort, ranging from 1.2% (Athens, Greece) to 10.9% (Madrid, Spain). Risk factors for allergic multimorbidity, identified with AICc, included family-allergy-score, odds ratio (OR) 1.50 (95% CI 1.32-1.70) per standard deviation; early-life allergy symptoms, OR 2.72 (2.34-3.16) for each symptom; and caesarean birth, OR 1.35 (1.04-1.76). Female gender, OR 0.72 (0.58-0.90); older siblings, OR 0.79 (0.63-0.99); and day care, OR 0.81 (0.63-1.06) were protective factors., Conclusion: Allergic multimorbidity should be regarded as an important chronic childhood disease in Europe. Some of the associated early-life factors are modifiable and may be considered for prevention strategies., (© 2021 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

A detailed understanding of the antibody response against SARS-CoV-2 is of high importance, especially with the emergence of novel vaccines. A multiplex-based assay, analyzing IgG, IgM, and IgA antibodies against the receptor binding domain (RBD), spike 1 (S1), and nucleocapsid proteins of the SARS-CoV-2 virus was set up. The multiplex-based analysis was calibrated against the Elecsys ® Anti-SARS-CoV-2 assay on a Roche Cobas ® instrument, using positive and negative samples. The calibration of the multiplex based assay yielded a sensitivity of 100% and a specificity of 97.7%. SARS-CoV-2 specific antibody levels were analyzed by multiplex in 251 samples from 221 patients. A significant increase in all antibody types (IgM, IgG, and IgA) against RBD was observed between the first and the third weeks of disease. Additionally, the S1 IgG antibody response increased significantly between weeks 1, 2, and 3 of disease. Class switching appeared to occur earlier for IgA than for IgG. Patients requiring hospital admission and intensive care had higher levels of SARS-CoV-2 specific IgA levels than outpatients. These findings describe the initial antibody response during the first weeks of disease and demonstrate the importance of analyzing different antibody isotypes against multiple antigens and include IgA when examining the immunological response to COVID-19., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Brynjolfsson, Sigurgrimsdottir, Einarsdottir, Bjornsdottir, Armannsdottir, Baldvinsdottir, Bjarnason, Gudlaugsson, Gudmundsson, Sigurdardottir, Love, Kristinsson and Ludviksson.)

Background: Hen's egg is one of the commonest causes of food allergy, but there are little data on its risk factors., Objective: To assess the risk factors, particularly eczema, for hen's egg allergy in the EuroPrevall birth cohort., Methods: In the pan-European EuroPrevall birth cohort, questionnaires were undertaken at 12 and 24 months or when parents reported symptoms. Children with suspected egg allergy were invited for skin prick testing, specific IgE assessment, and double-blind, placebo-controlled food challenge (DBPCFC) as indicated. Each egg allergy case (positive DBPCFC or egg-induced anaphylaxis) was allocated up to 2 age- and country-matched controls., Results: A total of 12,049 infants were recruited into the EuroPrevall birth cohort, and 9,336 (77.5%) were followed until 2 years. A total of 86 infants had egg allergy (84 by DBPCFC) and were matched with 140 controls. Independently associated with egg allergy were past/current eczema (adjusted odds ratio, 9.21; 95% CI, 2.65-32.04), Scoring Atopic Dermatitis (1.54 per 5 units; 1.28-1.86), antibiotics in the first week of life (6.17; 1.42-26.89), and current rhinitis (3.02; 1.04-8.78). Increasing eczema severity was associated with an increasing likelihood of egg allergy. Eczema was reported to have started 3.6 (SE, 0.5) months before egg allergy. Age of introduction of egg into the diet was not associated with egg allergy., Conclusions: Similar to peanut allergy, eczema was strongly associated with egg allergy development and the association increased with increasing eczema severity. The age of introduction of dietary egg was not a risk factor. The potential role of antibiotics in early life as a risk factor for egg allergy needs further examination., (Copyright © 2019. Published by Elsevier Inc.)

Background: Of the major peanut allergens, sensitivity to Ara h 2 has the highest prediction for clinical allergy. In this study, we evaluated sensitization to peanut components in Iceland and related Ara h 2-negative sensitization to clinical allergy., Methods: Ara h 1, Ara h 2, Ara h 3, Ara h 8, and Bet v 1 IgEs were measured (ImmunoCAP) in 220 peanut IgE (Pn-IgE)-positive serum samples. Ara h 2 IgE-negative individuals were invited to an open peanut challenge and evaluated for Ara h 6 and 9 sensitization (ISAC microarray)., Results: The Ara h 2 IgE-negative group (52.3%, 115/220) was older (p = 0.04) and more likely to have a history of pollen allergy than the Ara h 2-positive group (p < 0.001). Of the Ara h 2-negative participants, 24.3% were already consuming peanuts and 38.3% were unavailable. Of the 43 who underwent an open peanut challenge, 79% were negative, 14% were positive, and 7% were inconclusive. Those who reacted to peanuts had a higher Ara h 1 IgE than that of the tolerant participants, and 3 were positive to Ara h 6 IgE, and 2 of those subjects were monosensitized. Ara h 8 may have caused a positive reaction, while Ara h 9 did not., Conclusions: Half of the peanut-sensitized individuals in Iceland were not sensitized to the major allergen Ara h 2. Ara h 1, Ara h 3, and Ara h 6 sensitizations resulted in a positive open peanut challenge and they are therefore clinically important for individuals with a peanut allergy in Iceland., (© 2018 S. Karger AG, Basel.)

Background: Preschool wheeze is an important problem worldwide. No comparative population-based studies covering different countries have previously been undertaken., Objective: To assess the prevalence of early childhood wheeze across Europe and evaluate risk factors focusing on food allergy, breast feeding and smoke exposure., Methods: Infants from nine countries were recruited into the EuroPrevall birth cohort. At 12 and 24 months, data on wheeze, allergic signs/symptoms, feeding, smoke exposure, infections and day care attendance were collected using questionnaires. Poisson regression was used to assess risk factors for wheeze., Results: 12 049 infants were recruited. Data from the second year of life were available in 8805 (73.1%). The prevalence of wheeze in the second year of life ranged from <2% in Lodz (Poland) and Vilnius (Lithuania) to 13.1% (95% CI 10.7% to 15.5%) in Southampton (UK) and 17.2% (95% CI 15.0% 19.5%) in Reykjavik (Iceland). In multivariable analysis, frequent lower respiratory tract infections in the first and second years of life (incidence rate ratio (IRR) 1.9 (95% CI 1.3 to 2.6) and 2.5 (95% CI 1.9 to3.4), respectively), postnatal maternal smoking (IRR 1.6, 95% CI 1.1 to 2.4), day care attendance (IRR 1.6, 95% CI 1.1 to 2.5) and male gender (IRR 1.3, 95% CI 1.0 to 1.7) were associated with wheeze. The strength of their association with wheeze differed between countries. Food allergy and breast feeding were not independently associated with wheeze., Conclusion: The prevalence of early childhood wheeze varied considerably across Europe. Lower respiratory tract infections, day care attendance, postnatal smoke exposure and male gender are important risk factors. Further research is needed to identify additional modifiable risk factors that may differ between countries., Competing Interests: Competing interests: GR received grants from the EU FP6 Programme and UK Food Standards Agency during the conduct of the study; KEG has received educational grants from Nutrica and speaker fees from Nutrica and Abbott; TK has received grants from the EU FP7 Programme outside of the submitted work; STS received grants from Landspitali University Hospital Science Fund, GlaxoSmithKline and the Icelandic Student Innovation Fund during the conduct of the study and has received non-financial support from Novartis and Thermo Fisher outside of the submitted work; ENCM has received grants from the UK Biological and Biotechnological Sciences Research Council, DBV Technologies, Reacta Biotech Ltd, the Medical Research Council, Innovate and the North West Lung Centre Charity outside of the submitted work and is founding director of Reacta Biotech Ltd; KB has received funding for research activities from the European Union, German Research Foundation, Berliner Sparkasse, BEA-Stiftung, Food Allergy and Anaphylaxis Network, Food Allergy Initiative, Danone, Thermo Fisher and DST Diagnostics. Other authors have no competing interests to declare., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Consumption of oily fish or fish oil during pregnancy, lactation and infancy has been linked to a reduction in the development of allergic diseases in childhood., Methods: In an observational study, Icelandic children (n = 1304) were prospectively followed from birth to 2.5 years with detailed questionnaires administered at birth and at 1 and 2 years of age, including questions about fish oil supplementation. Children with suspected food allergy were invited for physical examinations, allergic sensitization tests, and a double-blind, placebo-controlled food challenge if the allergy testing or clinical history indicated food allergy. The study investigated the development of sensitization to food and confirmed food allergy according to age and frequency of postnatal fish oil supplementation using proportional hazards modelling., Results: The incidence of diagnosed food sensitization was significantly lower in children who received regular fish oil supplementation (relative risk: 0.51, 95% confidence interval: 0.32-0.82). The incidence of challenge-confirmed food allergy was also reduced, although not statistically significant (0.57, 0.30-1.12). Children who began to receive fish oil in their first half year of life were significantly more protected than those who began later (P = .045 for sensitization, P = .018 for allergy). Indicators of allergy severity decreased with increased fish oil consumption (P = .013). Adjusting for parent education and allergic family history did not change the results., Conclusion: Postnatal fish oil consumption is associated with decreased food sensitization and food allergies in infants and may provide an intervention strategy for allergy prevention., (© 2018 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Background: Blinded food challenges are considered the current gold standard for the diagnosis of food allergies. We used data from a pan-European multicenter project to assess differences between study centers, aiming to identify the impact of subjective aspects for the interpretation of oral food challenges., Methods: Nine study centers of the EuroPrevall birth cohort study about food allergy recruited 12 049 newborns and followed them for up to 30 months in regular intervals. Intensive training was conducted and every center visited to ensure similar handling of the protocols. Suspected food allergy was clinically evaluated by double-blind, placebo-controlled food challenges using a nine dose escalation protocol. The primary challenge outcomes based on physician's appraisal were compared to documented signs and symptoms., Results: Of 839 challenges conducted, study centers confirmed food allergy in 15.6% to 53.6% of locally conducted challenges. Centers reported 0 to 16 positive placebo challenges. Worsening of eczema was the most common sign when challenged with placebo. Agreement between documented objective signs and the challenge outcome assigned by the physician was heterogeneous, with Cohen's kappa spanning from 0.42 to 0.84., Conclusions: These differences suggest that the comparison of food challenge outcomes between centers is difficult despite common protocols and training. We recommend detailed symptom assessment and documentation as well as objective sign-based challenge outcome algorithms to assure accuracy and comparability of blinded food challenges. Training and supervision of staff conducting food challenges is a mandatory component of reliable outcome data., (© 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Background: Cow's milk allergy (CMA) is one of the most commonly reported childhood food problems. Community-based incidence and prevalence estimates vary widely, due to possible misinterpretations of presumed reactions to milk and differences in study design, particularly diagnostic criteria., Methods: Children from the EuroPrevall birth cohort in 9 European countries with symptoms possibly related to CMA were invited for clinical evaluation including cows' milk-specific IgE antibodies (IgE), skin prick test (SPT) reactivity and double-blind, placebo-controlled food challenge., Results: Across Europe, 12 049 children were enrolled, and 9336 (77.5%) were followed up to 2 years of age. CMA was suspected in 358 children and confirmed in 55 resulting in an overall incidence of challenge-proven CMA of 0.54% (95% CI 0.41-0.70). National incidences ranged from 1% (in the Netherlands and UK) to <0.3% (in Lithuania, Germany and Greece). Of all children with CMA, 23.6% had no cow's milk-specific IgE in serum, especially those from UK, the Netherlands, Poland and Italy. Of children with CMA who were re-evaluated one year after diagnosis, 69% (22/32) tolerated cow's milk, including all children with non-IgE-associated CMA and 57% of those children with IgE-associated CMA., Conclusions: This unique pan-European birth cohort study using the gold standard diagnostic procedure for food allergies confirmed challenge-proven CMA in <1% of children up to age 2. Affected infants without detectable specific antibodies to cow's milk were very likely to tolerate cow's milk one year after diagnosis, whereas only half of those with specific antibodies in serum 'outgrew' their disease so soon., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: The FAST (food allergy-specific immunotherapy) project aims at developing safe and effective subcutaneous immunotherapy for fish allergy, using recombinant hypoallergenic carp parvalbumin, Cyp c 1., Objectives: Preclinical characterization and good manufacturing practice (GMP) production of mutant Cyp (mCyp) c 1., Methods: Escherichia coli-produced mCyp c 1 was purified using standard chromatographic techniques. Physicochemical properties were investigated by gel electrophoresis, size exclusion chromatography, circular dichroism spectroscopy, reverse-phase high-performance liquid chromatography and mass spectrometry. Allergenicity was assessed by ImmunoCAP inhibition and basophil histamine release assay, immunogenicity by immunization of laboratory animals and stimulation of patients' peripheral blood mononuclear cells (PBMCs). Reference molecules were purified wild-type Cyp c 1 (natural and/or recombinant). GMP-compliant alum-adsorbed mCyp c 1 was tested for acute toxicity in mice and rabbits and for repeated-dose toxicity in mice. Accelerated and real-time protocols were used to evaluate stability of mCyp c 1 as drug substance and drug product., Results: Purified mCyp c 1 behaves as a folded and stable molecule. Using sera of 26 double-blind placebo-controlled food-challenge-proven fish-allergic patients, reduction in allergenic activity ranged from 10- to 5,000-fold (1,000-fold on average), but with retained immunogenicity (immunization in mice/rabbits) and potency to stimulate human PBMCs. Toxicity studies revealed no toxic effects and real-time stability studies on the Al(OH)3-adsorbed drug product demonstrated at least 20 months of stability., Conclusion: The GMP drug product developed for treatment of fish allergy has the characteristics targeted for in FAST: i.e. hypoallergenicity with retained immunogenicity. These results have warranted first-in-man immunotherapy studies to evaluate the safety of this innovative vaccine., (© 2015 S. Karger AG, Basel.)

Purpose: Primary immunodeficiencies (PID) are rare heterogeneous diseases. Little is known about the prevalence of PID in Iceland and no national registry exists. The aim of the study was to describe the epidemiology of PID in Iceland., Methods: Using The European Society's for Immunodeficiencies (ESID) criteria for PID, information about individuals with a known PID between 1990 and 2010 in Iceland were collected from inpatient registries of the National University Hospital of Iceland, the Department of Immunology and from clinical immunologists. Selective IgA deficiency, mannan binding lectin deficiency and secondary immunodeficiencies were excluded, Results: Sixty six individuals met the study criteria, 35 of them (53%) were females. Four patients died during the study period from PID- or treatment related complications and two moved abroad. In the beginning of 2011 there were 60 individuals living in Iceland with a known PID diagnosis meeting ESID's criteria. Estimated prevalence for PID in the Icelandic population of 318.452 habitants was 18.8 for 100.000 inhabitants. Predominantly antibody disorders comprised the largest category of PID in Iceland., Conclusions: The prevalence of PID is high in Iceland compared to reports from other nations. Our patient data are easily accessible and a central laboratory measures the immune parameters. This high prevalence may indicate that PID is more common than generally recognized.

Assessing maternal dietary habits across Europe during pregnancy in relation to their national pregnancy recommendations. A collaborative, multi-centre, birth cohort study in nine European countries was conducted as part of European Union funded EuroPrevall project. Standardised baseline questionnaire data included details of food intake, nutritional supplement use, exposure to cigarette smoke during pregnancy and socio-demographic data. Pregnancy recommendations were collected from all nine countries from the appropriate national organisations. The most commonly taken supplement in pregnancy was folic acid (55.6 % Lithuania-97.8 % Spain) and was favoured by older, well-educated mothers. Vitamin D supplementation across the cohort was very poor (0.3 % Spain-5.1 % Lithuania). There were significant differences in foods consumed in different countries during pregnancy e.g. only 2.7 % Dutch mothers avoided eating peanut, while 44.4 % of British mothers avoided it. Some countries have minimal pregnancy recommendations i.e. Lithuania, Poland and Spain while others have similar, very specific recommendations i.e. UK, the Netherlands, Iceland, Greece. Allergy specific recommendations were associated with food avoidance during pregnancy [relative rate (RR) 1.18 95 % CI 0.02-1.37]. Nutritional supplement recommendations were also associated with avoidance (RR 1.08, 1.00-1.16). Maternal dietary habits and the use of dietary supplements during pregnancy vary significantly across Europe and in some instances may be influenced by national recommendations.

Background: Pneumococcal polysaccharide vaccine (PPV) is used in children at high risk of IPD. PPV is generally not considered to induce immunologic memory, whereas pneumococcal conjugate vaccines (PCVs) elicit protective antibody responses in infants and induce immunologic memory. Little is known about the characteristics of immune responses to PCV in children who previously received PCV and PPV in series., Objective: To characterize immune responses to 13-valent pneumococcal CRM197 conjugate vaccine (PCV13; serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) in children vaccinated in infancy with 9-valent pneumococcal-meningococcal C-CRM197 conjugate combination vaccine (PCV9-MnCC), followed by a toddler dose of PCV9-MnCC or 23-valent pneumococcal polysaccharide vaccine (PPV23)., Methods: Children (n=89) who received PCV9-MnCC in infancy and PPV23 or PCV9-MnCC at age 12 months in a previous (2002-2003) study were vaccinated at age 7.5 years with PCV13; groups PPV23/PCV13 (n=50) and PCV9/PCV13 (n=39). Immunoglobulin (Ig)G antibodies, avidity, and opsonophagocytic activity (OPA) were measured before and at 1 and 4 weeks postvaccination., Results: One week postvaccination, IgG levels increased significantly for all serotypes in both groups, and >97% of vaccinees achieved IgG ≥0.35μg/ml 4 weeks after PCV13 vaccination. The PCV9/PCV13 group had higher IgG responses compared with the PPV23/PCV13 group. The upper limits of the 95% confidence intervals of the PPV23/PCV13:PCV9/PCV13 IgG geometric mean concentration ratios were <1.0 for serotypes 1, 4, 5, 9V, 18C, and 23F at 1 week. OPA and avidity results supported these findings., Conclusions: PPV23 vaccination of toddlers may compromise subsequent responses to pneumococcal conjugate vaccines. The clinical relevance of this finding is unclear., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Selective IgA deficiency (SIgAD) is the most common primary immunodeficiency in Caucasians with a prevalence of 1/600 and is generally considered a mild disorder. In this study, the clinical status of 32 adults with SIgAD was investigated and compared to 63 age- and gender matched controls, randomly selected from a population database. The SIgAD individuals reported significantly more often contracting various upper and lower respiratory infections, with 8 (25.0 %) having been diagnosed with ≥1 pneumonia in the preceding two years, compared to one (1.6 %) control (p < 0.001). Furthermore, the SIgAD individuals were found to have increased proneness to infections and increased prevalence of allergic diseases and autoimmunity, with a total of 84.4 % being affected by any of these diseases, compared to 47.6 % of the controls (p < 0.01). This study challenges the common statement of SIgAD being a mild form of immunodeficiency. It also highlights the importance of using matched controls in PID clinical research to better detect clinically important manifestations.

The FAST project (Food Allergy Specific Immunotherapy) aims at the development of safe and effective treatment of food allergies, targeting prevalent, persistent and severe allergy to fish and peach. Classical allergen-specific immunotherapy (SIT), using subcutaneous injections with aqueous food extracts may be effective but has proven to be accompanied by too many anaphylactic side-effects. FAST aims to develop a safe alternative by replacing food extracts with hypoallergenic recombinant major allergens as the active ingredients of SIT. Both severe fish and peach allergy are caused by a single major allergen, parvalbumin (Cyp c 1) and lipid transfer protein (Pru p 3), respectively. Two approaches are being evaluated for achieving hypoallergenicity, i.e. site-directed mutagenesis and chemical modification. The most promising hypoallergens will be produced under GMP conditions. After pre-clinical testing (toxicology testing and efficacy in mouse models), SCIT with alum-absorbed hypoallergens will be evaluated in phase I/IIa and IIb randomized double-blind placebo-controlled (DBPC) clinical trials, with the DBPC food challenge as primary read-out. To understand the underlying immune mechanisms in depth serological and cellular immune analyses will be performed, allowing identification of novel biomarkers for monitoring treatment efficacy. FAST aims at improving the quality of life of food allergic patients by providing a safe and effective treatment that will significantly lower their threshold for fish or peach intake, thereby decreasing their anxiety and dependence on rescue medication.

Background/aim: The true prevalence and risk factors of food allergies in children are not known because estimates were based predominantly on subjective assessments and skin or serum tests of allergic sensitization to food. The diagnostic gold standard, a double-blind placebo-controlled food provocation test, was not performed consistently to confirm suspected allergic reactions in previous population studies in children. This protocol describes the specific aims and diagnostic protocol of a birth cohort study examining prevalence patterns and influential factors of confirmed food allergies in European children from different regions., Methods: Within the collaborative translational research project EuroPrevall, we started a multi-center birth cohort study, recruiting a total of over 12 000 newborns in nine countries across Europe in 2005-2009. In addition to three telephone interviews during the first 30 months, parents were asked to immediately inform the centers about possible allergic reactions to food at any time during the follow-up period., Results: All children with suspected food allergy symptoms were clinically evaluated including double-blind placebo-controlled food challenge tests. We assessed sensitization to different food allergens by measurements of specific serum immunoglobulin E and skin prick tests, collect blood, saliva or buccal swabs for genetic tests, breast milk for measurement of food proteins/cytokines, and evaluate quality-of-life and economic burden of families with food allergic children., Conclusions: This birth cohort provides unique data on prevalence, risk factors, quality-of-life, and costs of food allergies in Europe, leading to the development of more informed and integrated preventative and treatment strategies for children with food allergies.

The influence of age on the generation and persistence of specific memory B cells after vaccination with Neisseria meningitidis type C polysaccharide (MenC-PS) conjugate is unknown. MenC-PS-specific B cells could be directly enumerated by fluorochrome-labeled MenC-PS and flow cytometry in blood up to at least 4 years after vaccination, ranging from 0.01% to 0.78% of total B cells and did not correlate with age at vaccination. The percentage of MenC-specific memory B cells out of total memory B cells correlated with total MenC-specific B-cells and with frequencies of IgA(+) plus IgG(+) MenC-specific AbSC, but not with MenC-specific Ab., (Copyright 2010 Elsevier Ltd. All rights reserved.)

This randomized trial compares safety and immunogenicity when vaccinating infants with a pneumococcal-meningococcal conjugate vaccine in two doses vs. three doses. Infants (N=223) received 9vPnC-MnCC (CRM197-conjugated pneumococcal serotypes 1, 4, 5, 6B, 9V, 14, 18C, 19F, 23F and meningococcal C polysaccharides) either at 3 and 5 or 3, 4 and 5 months and a booster with either 9vPnC-MnCC or 23-valent pneumococcal-polysaccharide vaccine (23vPPS) and CRM197-MnCC, at 12 months. Safety was monitored and IgG measured at 3, 6, 12 and 13 months in all subjects and serum bactericidal activity (SBA) in half. The 9vPnC-MnCC vaccine was safe and induced significant IgG to all components. Three doses induced higher antibody GMCs (geometric mean concentrations) at 6 months to seven of nine pneumococcal serotypes. This was most significant for 6B and 23F (p<0.001), that also showed lower rate of responders>0.35 (6B, 23F) and >0.5 microg/mL (6B). Antibody GMCs remained lower following 9vPnC-MnCC booster in subjects primed with two doses although only significant for serotype 18C. Significant memory responses were observed 1 week after the 23vPPS toddler dose. MnCC-IgG GMC was lower after two doses, however with comparable SBA. This study shows that the 9vPnC-MnCC vaccine is safe and induces successful immunological memory, whether given in two or three primary doses.

Background: There is uncertainty regarding the prevalence of allergies to plant food., Objective: To assess the prevalence of allergies to plant food according to the different subjective and objective assessment methods., Methods: Our systematic search of population-based studies (since 1990) in the literature database MEDLINE focused on fruits, vegetables/legumes, tree nuts, wheat, soy, cereals, and seeds. Prevalence estimates were categorized by food item and method used (food challenges, skin prick test, serum IgE, parent/self-reported symptoms), complemented by appropriate meta-analyses., Results: We included 36 studies with data from a total of over 250,000 children and adults. Only 6 studies included food challenge tests with prevalences ranging from 0.1% to 4.3% each for fruits and tree nuts, 0.1% to 1.4% for vegetables, and < 1% each for wheat, soy, and sesame. The prevalence of sensitization against any specific plant food item assessed by skin prick test was usually < 1%, whereas sensitization assessed by IgE against wheat ranged as high as 3.6% and against soy as high as 2.9%. For fruit and vegetables, prevalences based on perception were generally higher than those based on sensitization, but for wheat and soy in adults, sensitization was higher. Meta-analyses showed significant heterogeneity between studies regardless of food item or age group., Conclusion: Population-based prevalence estimates for allergies to plant products determined by the diagnostic gold standard are scarce. There was considerable heterogeneity in the prevalence estimates of sensitization or perceived allergic reactions to plant food.

Background: There is uncertainty about the prevalence of food allergy in communities., Objective: To assess the prevalence of food allergy by performing a meta-analysis according to the method of assessment used., Methods: The foods assessed were cow's milk, hen's egg, peanut, fish, shellfish, and an overall estimate of food allergy. We summarized the information in 5 categories: self-reported symptoms, specific IgE positive, specific skin prick test positive, symptoms combined with sensitization, and food challenge studies. We systematically searched MEDLINE and EMBASE for publications since 1990. The meta-analysis included only original studies. They were stratified by age groups: infant/preschool, school children, and adults., Results: A total of 934 articles were identified, but only 51 were considered appropriate for inclusion. The prevalence of self-reported food allergy was very high compared with objective measures. There was marked heterogeneity between studies regardless of type of assessment or food item considered, and in most analyses this persisted after age stratification. Self-reported prevalence of food allergy varied from 1.2% to 17% for milk, 0.2% to 7% for egg, 0% to 2% for peanuts and fish, 0% to 10% for shellfish, and 3% to 35% for any food., Conclusion: There is a marked heterogeneity in the prevalence of food allergy that could be a result of differences in study design or methodology, or differences between populations., Clinical Implications: We recommend that measurements be made by using standardized methods, if possible food challenge. We need to be cautious in estimates of prevalence based only on self-reported food allergy.

Background: Previous studies show that 6-9% of young adults in Reykjavik are sensitised to the house dust mite (HDM) Dermatophagoides pteronyssinus (D. pteronyssinus). However, only negligible amounts of HDM and HDM allergens were detected in their homes. The study investigates what characterizes these individuals., Methods: We investigated all participants in the European Community Respiratory Health Surveys I and II (ECRHS I and II) with D. pteronyssinus specific IgE, in the years 1991-92. A grass positive but D. pteronyssinus negative control group was recruited from the same cohort. A detailed questionnaire was administered and the specific IgE (Pharmacia CAP system) against six D. pteronyssinus cross-reactive allergens was measured., Results: Of 601 ECRHS I participants with available IgE results, 88% returned for ECRHS II, 8.4 years later. Of 49 individuals with D. pteronyssinus specific IgE in ECRHS I, 24 had become negative in ECRHS II. Compared with controls, HDM sensitive subjects were more often men who had lived on farms or kept aquaria fish in childhood. Of those with specific IgE against D. pteronyssinus in ECRHS I and II, 75% had detectable IgE antibodies (>or=0.35 kU/l) to cross-reactive allergens compared with none in the control group (p<0.0001): Lepidoglyphus destructor (L. destructor) (67%), shrimp (58%), cockroach (33%), mosquito (17%), tropomyosin (17%) and blood worm (4%)., Conclusions: Icelanders with specific IgE to D. pteronyssinus are more often men who spent time on farms in childhood and today have high prevalence of IgE antibodies cross-reactive to D. pteronyssinus.

Background: Development of protein-conjugated pneumococcal vaccines for infants has led to formulations that are immunogenic in the age group at highest risk for pneumococcal diseases. This study focuses on the search for an optimal formulation., Methods: In a randomized trial Icelandic infants (n = 160) were immunized at age 3, 4 and 6 months with one of two octavalent pneumococcal conjugate vaccines (serotypes 3, 4, 6B, 9V, 14, 18C, 19F and 23F conjugated to diphtheria toxoid (PncD) or tetanus protein (PncT) followed with a booster of either the same conjugate or 23-valent polysaccharide vaccine at 13 months. Safety data were collected after each vaccination, and IgG responses (enzyme-linked immunosorbent assay) were measured at 3, 4, 6, 7, 13 and 14 months., Results: Both conjugates were safe and caused fewer local reactions than the routine vaccines (P < 0.0001). At 7 months both groups had significant IgG response to all serotypes. The geometric mean concentration range was 0.35 to 4.09 and 0.65 to 3.38 microg/ml for PncD and PncT, respectively, with 88.2 to 100% and 92.4 to 100% of subjects reaching > or = 0.15 microg/ml. The PncD gave better primary responses to serotypes 3, 9V and 18C, whereas PncT gave better response to serotype 4. Similar responses were induced to the other serotypes. Good booster IgG responses were obtained in all vaccine groups; 97.5 to 100% of subjects reached > or = 1 microg/ml., Conclusions: Both octavalent pneumococcal conjugates were safe and immunogenic in infants. Based on the results from this and similar trials, a mixed diphtheria and tetanus pneumococcal conjugate vaccine was designed to provide the optimal immune response to each serotype.

Streptococcus pneumoniae serogroup 6 is an important cause of respiratory tract disease worldwide. Vaccination with 6B polysaccharide induces antibody response to the cross-reacting serotype 6A, but the protective capacity of 6A antibodies induced in infants remains unknown. In this study, passive immunization with serum samples obtained from infants vaccinated with an octavalent polysaccharide protein conjugate vaccine, PncT, protected mice against bacteremia and/or lung infection caused by intranasal challenge with serotypes 6B and 6A. Protective infant serum samples had significantly higher serotype-specific IgG levels and opsonic activity than did nonprotective serum samples. The protective level to either serotype was approximately 1 microg of specific IgG antibodies injected per mouse (corresponding to approximately 0.3 microg/mL). The protection was strongly related to opsonophagocytic antibody levels measured in vitro. These results demonstrate that PncT induces antibodies in infants that protect mice against invasive disease caused by the homologous serotype and by the cross-reacting serotype 6A.

Streptococcus pneumoniae is a major respiratory pathogen of infants, children, and the elderly. Polysaccharide vaccines have been useful in adult populations but do not elicit protective immunity in infants and young children. To enhance their immunogenicity, vaccines of pneumococcal polysaccharides conjugated to proteins are being developed. In this study antibody levels and opsonic activities were compared in sera of infants and adults injected with pneumococcal polysaccharide type 6B (Pn6B) conjugated to tetanus toxoid (TT) (Pn6B-TT). Healthy infants were injected with Pn6B-TT; group A was injected at 3, 4, and 6 months of age, and group B was injected at 7 and 9 months of age. A booster injection was given at 18 months. Adults were injected once. Antibodies were measured by enzyme-linked immunosorbent assay and radioimmunoassay, and their functional activities were measured by opsonophagocytosis of radiolabelled pneumococci. In adults, increases in immunoglobulin M (IgM), IgG, IgA, IgG1, and IgG2 to Pn6B were observed. Infants reached adult levels of IgG1 anti-Pn6B after the primary injections. After the booster injection the infant groups had total IgG- and IgM-Pn6B antibody levels similar to those of adults. After the booster injection, IgG1 was the dominant infant anti-Pn6B isotype and at a level higher than in vaccinated adults, but IgA and IgG2 antibodies remained at very low levels. Opsonic activity increased significantly after Pn6B-TT injections; the highest infant sera showed opsonic activity comparable to that of vaccinated adults. Overall, opsonic activity correlated best with total and IgG anti-Pn6B antibodies (r = 0.741, r = 0.653, respectively; n = 35) and was highest in sera with high levels of all Pn6B antibody isotypes. The results indicate the protective potential of a pneumococcal 6B polysaccharide protein conjugate vaccine for young infants.

Background: Streptococcus pneumoniae is a major cause of meningitis, bacteremia, pneumonia and otitis media. Pneumococcal polysaccharides are not immunogenic in infants, but improved immunogenicity of polysaccharide-protein conjugates has been demonstrated. Antibiotic-resistant pneumococci have increased the need for an effective vaccine., Objective: To study the safety and immunogenicity of a pneumococcal type 6B polysaccharidetetanus toxoid conjugate (Pn6B-TT) in infants and to assess the function of antibodies., Methods: Healthy infants were injected, Group A at 3, 4 and 6 months (n = 21) and Group B at 7 and 9 months (n = 19). Booster injection was given at 18 months. Antibodies were measured by enzyme-linked immunosorbent assay and radioimmunoassay, and functional activity was measured by opsonization of radiolabeled pneumococci. Nasopharyngeal cultures were obtained., Results: No significant adverse reactions were observed. Pn6B-IgG (enzyme-linked immunosorbent assay) increased to a geometric mean of 0.62 microgram/ml (P = 0.367, compared with prevaccination titers) in Group A at 7 months and 1.22 micrograms/ml (P < 0.001) in Group B at 10 months. Total Pn6B antibodies (radioimmunoassay) were 44 ng of antibody N/ml (P < 0.053) in Group A and 211 ng of antibody N/ml (P < 0.001) in Group B. A smaller increase in IgM and IgA anti-Pn6B was observed. Reinjection at 18 months elicited booster responses in total and IgG anti-Pn6B; 62% of those in Group A and 79% of those in Group B had > 300 ng of antibody N/ml. Opsonic activity, after initial and booster vaccinations, correlated with Pn6B-antibody titers. Three infants with nasopharyngeal cultures repeatedly positive for serogroup 6 had poor serum IgG responses., Conclusion: Our results demonstrate that Pn6B-TT is safe, elicits functional antibodies and memory responses in infants.