SARS-CoV-2-Specific Antibody Detection for Seroepidemiology: A Multiplex Analysis Approach Accounting for Accurate Seroprevalence

Background. The COVID-19 pandemic necessitates better understanding of the kinetics of antibody production induced by infection with SARS-CoV-2. We aimed to develop a high-throughput multiplex assay to detect antibodies to SARS-CoV-2 to assess immunity to the virus in the general population. Methods. Spike protein subunits S1 and receptor binding domain, and nucleoprotein were coupled to microspheres. Sera collected before emergence of SARS-CoV-2 (n = 224) and of non-SARS-CoV-2 influenza-like illness (n = 184), and laboratory-confirmed cases of SARS-CoV-2 infection (n = 115) with various severities of COVID-19 were tested for SARS-CoV-2–specific IgG concentrations. Results. Our assay discriminated SARS-CoV-2–induced antibodies and those induced by other viruses. The assay specificity was 95.1%–99.0% with sensitivity 83.6%–95.7%. By merging the test results for all 3 antigens a specificity of 100% was achieved with a sensitivity of at least 90%. Hospitalized COVID-19 patients developed higher IgG concentrations and the rate of IgG production

Participation in and attitude towards the national immunization program in the Netherlands: data from population-based questionnaires

Contains fulltext : 108971.pdf (publisher's version ) (Open Access)BACKGROUND: Knowledge about the determinants of participation and attitude towards the National Immunisation Program (NIP) may be helpful in tailoring information campaigns for this program. Our aim was to determine which factors were associated with nonparticipation in the NIP and which ones were associated with parents' intention to accept remaining vaccinations. Further, we analyzed possible changes in opinion on vaccination over a 10 year period. METHODS: We used questionnaire data from two independent, population-based, cross-sectional surveys performed in 1995-96 and 2006-07. For the 2006-07 survey, logistic regression modelling was used to evaluate what factors were associated with nonparticipation and with parents' intention to accept remaining vaccinations. We used multivariate multinomial logistic regression modelling to compare the results between the two surveys. RESULTS: Ninety-five percent of parents reported that they or their child (had) participated in the NIP. Similarly, 95% reported they intended to accept remaining vaccinations. Ethnicity, religion, income, educational level and anthroposophic beliefs were important determinants of nonparticipation in the NIP. Parental concerns that played a role in whether or not they would accept remaining vaccinations included safety of vaccinations, maximum number of injections, whether vaccinations protect the health of one's child and whether vaccinating healthy children is necessary. Although about 90% reported their opinion towards vaccination had not changed, a larger proportion of participants reported to be less inclined to accept vaccination in 2006-07 than in 1995-96. CONCLUSION: Most participants had a positive attitude towards vaccination, although some had doubts. Groups with a lower income or educational level or of non-Western descent participated less in the NIP than those with a high income or educational level or indigenous Dutch and have been less well identified previously. Particular attention ought to be given to these groups as they contribute in large measure to the rate of nonparticipation in the NIP, i.e., to a greater extent than well-known vaccine refusers such as specific religious groups and anthroposophics. Our finding that the proportion of the population inclined to accept vaccinations is smaller than it was 10 years ago highlights the need to increase knowledge about attitudes and beliefs regarding the NIP

Umbilical vessels of preeclamptic women have low contents of both n-3 and n-6 long-chain polyunsaturated fatty acids

Background: Preeclampsia is characterized by enhanced platelet aggregation and vasoconstriction and is related to an elevated ratio of thromboxane A(2) to prostacyclin I-2. Objective: We investigated whether altered eicosanoid production in preeclamptic women could be explained by the fatty acid composition of umbilical vessel walls and platelets. Design: The fatty acid composition of maternal and umbilical platelets and of umbilical arteries and veins in 27 preeclamptic women and 24 normotensive women was determined. Between-group differences were analyzed with linear discriminant analysis, the Kruskal-Wallis test, or analysis of covariance with gestational age as the covariate. Results: Platelets of preeclamptic women contained lower amounts of 20:5n-3 and a higher ratio of 20:4n-6 to 20:5n-3 than did platelets of normotensive women. Additionally, linear discriminant analysis revealed higher amounts of 20:4n-6 in platelets of preeclamptic women. Umbilical arteries and veins in preeclamptic women contained lower amounts of long-chain polyunsaturated fatty acids (PUFAs) of the n-3 series, n-6 long-chain PUFAs, and 20:3n-6 than did umbilical arteries and veins of normotensive women. Umbilical arteries also had lower amounts of 20:4n-6, higher amounts of 20:3n-9, and a higher ratio of 20:3n-9 to 20:4n-6. Conclusions: Low amounts of long-chain n-3 and n-6 PUFAs in umbilical vessels of preeclamptic women with adequate n-6 status may indicate insufficient transplacental transfer of long-chain PUFAs, The low amounts of 20:4n-6, high amounts of 20,3n-9, and high ratio of 20:3n-9 to 20:4n-6 in umbilical arteries may unfavorably affect local prostacyclin production. Low amounts of 20:3n-6 in umbilical arteries and veins and low amounts of 20:5n-3 in maternal platelets may contribute to the dominance of eicosanoids derived from 20:4n-6

PIENTER 2-project: tweede onderzoek naar de bescherming tegen infectieziekten waartegen in het Rijksvaccinatieprogramma wordt ingeent

Dit rapport bevat een erratum d.d. 2 maart 2010In 2006 en 2007 heeft het RIVM in opdracht van het ministerie van VWS het tweede PIENTER-project uitgevoerd. Dit staat voor Peiling Immunisatie Effect Nederland ter Evaluatie van het Rijksvaccinatieprogramma. Het doel is te onderzoeken of Nederland goed beschermd is tegen infectieziekten waartegen in het Rijksvaccinatieprogramma (RVP) wordt ingeent. De resultaten van het onderzoek kunnen bijdragen aan eventuele verbeteringen van het RVP en zullen groepen personen met minder goede bescherming tegen infectieziekten aan het licht brengen. Dit rapport beschrijft de opzet van dit onderzoek en geeft achtergrondinformatie over de deelnemers. De deelnemers waren tussen de 0 en 79 jaar en woonden verspreid door heel Nederland. Zij hebben een vragenlijst ingevuld over hun persoonlijke gegevens, gezondheid en doorgemaakte ziekten. Daarnaast is er bloed afgenomen om te kijken hoeveel antistoffen de deelnemers hebben tegen de ziekten uit het RVP. Tot slot is aan hen gevraagd welke inentingen ze hebben gehad. Er is een extra groep mensen uitgenodigd uit de groep niet-westerse migranten en uit de groep orthodox-gereformeerden die vaccinatie afwijzen. Dit onderzoek verschaft inzicht in de mate van afweer tegen ziekten die mensen verkrijgen nadat ze zijn gevaccineerd of de ziekte hebben doorgemaakt, en in het voorkomen van infectieziekten. In totaal zijn er 24.147 personen uitgenodigd en daarvan was 33 procent bereid om mee te doen aan het onderzoek. Van 7904 personen is bloed aanwezig dat in het laboratorium zal worden onderzocht op de aanwezigheid van antistoffen tegen alle infectieziekten van het RVP en andere infectieziekten. De resultaten van het bloedonderzoek en de vragenlijst gegevens zullen worden vergeleken met die van het eerste PIENTER-onderzoek, dat tien jaar eerder is uitgevoerd, en zullen apart worden gerapporteerd.In 2006 and 2007 the RIVM carried out the second PIENTER-study by order of the Ministry of Health, Welfare and Sports (VWS). PIENTER is a Dutch acronym for: Peiling Immunisatie Effect Nederland Ter Evaluatie van het Rijksvaccinatieprogramma. The aim of this study is to gain insight into how well the Dutch population is protected against vaccine-preventable diseases through the national immunization programme (NIP). The results will enable further improvements of the immunization programme to be made as well as identifying those population groups who are less protected. This report describes the design of the study and provides background information on the participants. The people who took part were between 0-79 years old and lived scattered throughout the Netherlands. They completed a questionnaire on their personal details, their state of health and any diseases they have had in the past. In addition, blood samples were taken from the participants to determine the antibody levels of the diseases covered by the programme. Finally, they were asked which vaccinations they have already had. An extra group of non-Western migrants and a group of orthodox-reformed individuals, who refuse vaccination on religious grounds, were also invited to participate. The study provides insight into disease protection levels that were obtained either through vaccination or because a person has had the disease itself. It also provides information on the spread of infectious diseases. In total, 24,147 people were invited to take part in the study. Thirty-three percent of those asked, agreed to participate. Currently, blood samples are available from 7,904 people that will be tested for the presence of antibodies against all of the infectious diseases covered by the programme as well as other infectious diseases. The blood results and questionnaire information will be compared with the results of the first PIENTER-study, which was performed ten years ago. The data will be reported separately.VW

Effect of three low-dose fish oil supplements, administered during pregnancy, on neonatal long-chain polyunsaturated fatty acid status at birth

Adequate long-chain polyunsaturated fatty acid (LCP) status during pregnancy is important. We studied the effect of three low-dose fish oil supplements, administered during uncomplicated pregnancy, on neonatal LCP status at term delivery. Supplements were administered from the second trimester to delivery, either as fish oil capsules ('fish-1': 336 mg LCP omega3, n=15; and 'fish-3': 1,008 mg LCP omega3, n=20) or milk-based supplement ('Mum': 528 mg LCP omega3, n=24). Fifty-seven untreated women served as controls. Fatty acids of umbilical veins (UV) and arteries (UA) were measured. The fish-1 group showed no differences, compared to controls. The Mum group had higher 20:5 omega3,22:5 omega3,22:6 omega3, LCP omega3 and 22:6 omega3/22:5 omega6 in Wand UA. The fish-3 group had higher 22:5 omega3 and 22:6 omega3 (UA), LCP omega3 and 22:6 omega3/22:5 omega6 (UV and UA) and 20:3 omega6 (UV). A 500-1000 mg daily LCP omega3 supplement, taken either as a milk-based supplement or fish oil capsules, effectively increases fetal LCP omega3 status, without affecting LCP omega6 status. (C) 2001 Harcourt Publishers Ltd

BMR vaccin bij 14 maanden oude kinderen, intramusculaire versus subcutane toediening

In this study we compared the recommended subcutaneous administration of the RIVM MMR vaccine with the intramuscular administration for both safety and immunogenicity. Study subjects were 14 months old children, living in Amersfoort or Utrecht, who were eligible for their first MMR vaccination. The participants (N=67) were 'at random' assigned to one of the study groups based on route of administration of the vaccine (intramuscular or subcutaneous). Pain immediately after vaccination was the most reported adverse reaction. Serious pain was more often reported after subcutaneous vaccination. But because of the low number of participants in this study it is only an indication without an exact statistical foundation. It is known that adverse reactions due to infection by the vaccine virus are often seen in the second week after the MMR vaccination. In this study we also found a peak in the general health complaints in the second week after vaccination. The route of administration of the vaccine did not influence these complaints. It is difficult to assess which complaints are directly related to the MMR vaccine, because they often can not be distinguished from symptoms of common diseases in 14 months old children. Both subcutaneous and intramuscular administered MMR vaccine induced a good immune response. The levels of the ELISA antibodies against mumps and rubella after subcutaneous vaccination are the same as those after intramuscular vaccination. The titres against measles were somewhat higher after subcutaneous vaccination as compared to those after intramuscular injection, both for ELISA antibodies as well as antibodies measured with the virus neutralisation assay. However, this difference was not statistically significant. Besides, the injection route had no effect on the percentages of children with antibodies above the protective level against mumps (92%), measles (100%) and rubella (100%). This study shows that inadvertent intramuscular administration of MMR vaccine is no reason for revaccination. In the future it can be considered to adjust the instructions for use of the RIVM MMR vaccine so that both subcutaneous and intramuscular vaccination are allowed.In deze studie is de gebruikelijke en in de bijsluiter geadviseerde subcutane toedieningsroute van het BMR vaccin vergeleken met intramusculaire toediening, zowel wat betreft veiligheid als immunogeniciteit. De studie populatie bestond uit 14 maanden oude kinderen uit Amersfoort of Utrecht die in aanmerking kwamen voor hun eerste BMR vaccinatie. De deelnemers (N=67) werden 'at random' verdeeld over twee onderzoeksgroepen gebaseerd op de toedieningswijze van het vaccin (intramusculair of subcutaan). Pijn direct na vaccinatie was de meest gemelde lokale reactie. Heftige pijn kwam wat vaker voor na subcutane injectie. Het aantal deelnemers is echter te klein om dit statistisch te onderbouwen. Bijwerkingen door de infectieverschijnselen, die door het vaccinvirus veroorzaakt kunnen worden, treden met name op in de tweede week na de BMR vaccinatie. Ook in dit onderzoek was een piek in de algemene gezondheidsklachten te zien in de tweede week na vaccinatie. Deze klachten waren onafhankelijk van de toedieningsroute van het vaccin. Het is echter moeilijk te bepalen welke klachten een direct gevolg van de BMR vaccinatie zijn, omdat deze vaak niet te onderscheiden zijn van symptomen van ziektes die bij 14 maanden oude kinderen veel voorkomen. te een goede immuunrespons op. De hoogte van ELISA titers tegen bof en rubella lijkt onafhankelijk van de toedieningsroute van het vaccin. De antistoffen tegen mazelen lagen na subcutane vaccinatie op een iets hoger niveau dan na intramusculaire vaccinatie, zowel voor antistoffen gemeten met ELISA als met de virusneutralisatie assay. Dit verschil was echter niet statistisch significant. De toedieningsroute was niet van invloed op de percentages kinderen met antistoffen boven het als beschermend beschouwde niveau tegen zowel bof (92%), mazelen (100%) als rubella (100%). Dit onderzoek toont aan dat er geen reden voor revaccinatie is, wanneer het BMR vaccin per ongeluk intramusculair toegediend is. In de toekomst kan mogelijkerwijs in de bijsluiter van het RIVM BMR vaccin opgenomen worden dat het vaccin zowel subcutaan als intramusculair toegediend mag worden

The impact of prenatal exposure to parasitic infections and to anthelminthic treatment on antibody responses to routine immunisations given in infancy: Secondary analysis of a randomised controlled trial

Background Chronic parasitic infections are associated with active immunomodulation which may include by-stander effects on unrelated antigens. It has been suggested that pre-natal exposure to parasitic infections in the mother impacts immunological development in the fetus and hence the offspring’s response to vaccines, and that control of parasitic infection among pregnant women will therefore be beneficial. Methodology/Principal findings We used new data from the Entebbe Mother and Baby Study, a trial of anthelminthic treatment during pregnancy conducted in Uganda, to further investigate this hypothesis. 2705 mothers were investigated for parasitic infections and then randomised to albendazole (400mg) versus placebo and praziquantel (40mg/kg) during pregnancy in a factorial design. All mothers received sulfadoxine/pyrimethamine for presumptive treatment of malaria. Offspring received Expanded Programme on Immunisation vaccines at birth, six, 10 and 14 weeks. New data on antibody levels to diphtheria toxin, three pertussis antigens, Haemophilus influenzae type B (HiB) and Hepatitis B, measured at one year (April 2004 –May 2007) from 1379 infants were analysed for this report. Additional observational analyses relating maternal infections to infant vaccine responses were also conducted. Helminth infections were highly prevalent amongst mothers (hookworm 43.1%, Mansonella 20.9%, Schistosoma mansoni 17.3%, Strongyloides 11.7%, Trichuris 8.1%) and 9.4% had malaria at enrolment. In the trial analysis we found no overall effect of either anthelminthic intervention on the measured infant vaccine responses. In observational analyses, no species was associated with suppressed responses. Strongyloidiasis was associated with enhanced responses to pertussis toxin, HiB and Hep B vaccine antigens. Conclusions/Significance Our results do not support the hypothesis that routine anthelminthic treatment during pregnancy has a benefit for the infant’s vaccine response, or that maternal helminth infection has a net suppressive effect on the offspring’s response to vaccines.