Quantitative analysis of pertussis, tetanus, and diphtheria antibodies in sera and breast milk from Tdap vaccinated women using a qualified multiplex assay.

Pertussis (whooping cough) is a reemergent, highly contagious respiratory infection of public health concern. Infants prior to initiation of their primary vaccination series are the most vulnerable to severe infection, and even death. Vaccination during pregnancy is an efficacious means of reducing infection in infants. This approach relies on boosting maternal immunity and passive transfer of antibodies to the infant via placenta and breast milk. Similarly, maternal vaccination post-partum can enhance maternal-infant immunity. To support the analysis of pertussis immunity in the context of maternal-infant immunization, we developed a high throughput multiplex assay for simultaneous quantification of serum IgG antibodies against pertussis vaccine antigens: pertussis toxin (PT), filamentous hemagglutinin (FHA), pertactin (PRN), and fimbriae (FIM2/3), and against tetanus (TT) and diphtheria toxoids (DT), using the Meso Scale Discovery (MSD) platform. The assay was qualified, and specificity, sensitivity, accuracy, precision, linearity, and robustness were demonstrated. The assay was subsequently adapted for quantification of IgG and IgA in breast milk. Applied to a serological survey of pregnant women living in the United States and sub-Saharan Africa, this method revealed differences in magnitude and breadth of antibody profile, consistent with history of vaccination. A longitudinal analysis of Tdap responses in women vaccinated post-partum demonstrated a rapid increase in serum IgG that remained elevated for up to 24 months. Likewise, high levels of vaccine-specific IgA and IgG antibodies were present in breast milk, although they exhibited faster decay. This multiplex MSD assay is a reliable and practical tool for quantification of pertussis, tetanus, and diphtheria antibodies in serum and breast milk in serosurveys or vaccine studies. IMPORTANCE: Pertussis (whooping cough) has reemerged in recent years. Vaccination during pregnancy is an effective approach to prevent illness during the first months of life. We developed a multiplex assay for quantification of pertussis, tetanus, and diphtheria serum antibodies using the Meso Scale Discovery (MSD) platform; the method was qualified, and specificity, precision, accuracy, linearity, and limits of quantification were defined. It was also adapted for quantification of antibodies in breast milk. We successfully determined serostatus in women from different regions and with different vaccination histories, as well as responses to Tdap in blood and breast milk post-partum. This is the first description of a multiplex assay for the quantification of pertussis, tetanus, and diphtheria antibodies in breast milk.

Successful transfer of passive immunity: the natural alternative to antibiotics for boosting the survival of intensively reared dairy goat kids.

In dairy operations, antibiotics have traditionally been used to treat, prevent, and control diseases. However, given the mounting global crisis of antimicrobial resistance (AMR), farmers are urged to re-assess and reduce their reliance on antibiotics. Thus, this randomized, double-blinded cohort study aimed to estimate the prevalence of failed and successful transfer of passive immunity (FTPI and STPI) in dairy goat kids reared under commercial conditions, and the effects of antibiotic metaphylaxis on the pre-weaning (≤42 d old) mortality in FTPI and STPI kids. Plasma concentration of immunoglobulin G at 1d old (pIgG-24 h) was measured in 747 male Saanen kids for the determination of FTPI and STPI (pIgG-24 h < 12 and ≥12 g/L, respectively). Kids were then randomly divided into two groups: those receiving a single penicillin injection at 1 d old (PEN), and those receiving no treatment (CTR). The mean (±SD) pIgG-24 h and initial BW (IBW) were 17 ± 9.8 g/L and 4.1 ± 0.64 kg. The prevalence of FTPI was 29% (220/747 kids). Gastrointestinal complications were the primary cause of death (41%), followed by septicemia (22%) and arthritis (17%). A single penicillin injection reduced preweaning mortality by 55% (10 vs 22%, PEN vs CTR). However, results suggest that such a decline was mainly driven by the improved survival rates among FTPI kids, which increased by 19% (from 62% in CTR-FTPI to 82% in PEN-FTPI), as opposed to an 8% increase among STPI kids (from 85% in CTR-STPI to 93% in PEN-STPI). Additionally, the odds of mortality ≤ 42 d old were threefold higher in the CTR-FTPI group when compared to both the CTR-STPI and PEN-FTPI groups, suggesting a potential parity between STPI and PEN for mortality rate reduction. Taken together, the results indicate that although metaphylactic antibiotics can halve preweaning mortality, similar improvements are likely to be achieved via increased STPI rates. Furthermore, by targeting metaphylactic interventions to high-risk groups (i.e., those displaying signs of inadequate colostrum intake and/or low birth BW), farmers could reduce treatment costs and mitigate AMR risks. While these findings carry considerable weight for commercial dairy goat practices, their applicability to other systems (i.e., extensive, semi-intensive, mohair, meat systems) warrants further investigation.

Maternally transmitted anti-measles antibodies, and susceptibility to disease among infants in Chandigarh, India: A prospective birth cohort study.

Prior to the age of measles vaccination, infants are believed to be protected against measles by passively transferred maternal antibodies. However, the quantity and quality of such protection have not been well established in the Indian setting. We undertook this study to characterize the transfer and decline in maternal anti-measles antibodies among infants, and determine their susceptibility to measles. In this population-based, birth-cohort study, we enrolled pregnant women and their newborn infants, from a catchment area of 30 Anganwadis in Chandigarh, India. We collected maternal blood at delivery, and infant blood samples at birth, and 3, 6, and 9 months of age. Anti-measles IgG antibodies were measured using quantitative ELISA. We assessed antibody decline using log-linear models. In total, 428 mother-infant dyads were enrolled, and data from 413 dyads were analyzed. At birth, 91.5% (95% CI: 88.8, 94.2) of infants had protective antibody levels, which declined to 26.3% (95% CI: 21.0%, 31.9) at 3 months, 3.4% (95% CI: 0.9, 5.9) at 6 months, and 2.1% (95% CI: 0.1, 4.1) at 9 months. Younger mothers transferred lower levels of antibodies to their infants. We concluded that the majority of infants are susceptible to measles as early as three months of age, much earlier than their eligibility to receive measles vaccination.

Epidemiología y características de la infección por SARS-COV-2 en el recién nacido y la gestante. Transferencia transplacentaria de inmunoglobulina / Epidemiology and characteristics of SARS-CoV-2 infection in the newborn and pregnant woman. Transplacemental transfer of immunoglobulins

Introducción La infección por SARS-CoV-2 durante la gestación y su repercusión en el recién nacido eran, en los primeros meses de la pandemia, desconocidas. Recientes estudios han aportado información sobre la afectación clínica en el recién nacido y su evolución. En este trabajo se muestra cómo varía la inmunidad pasiva en el recién nacido con relación al momento de infección SARS-CoV-2 materno. Población y método Estudio observacional, prospectivo y longitudinal en un hospital de tercer nivel. Se recogieron datos epidemiológicos y clínicos de las madres y sus recién nacidos desde mayo del 2020 hasta junio del 2021. Resultados Se ha incluido a un total de 109 madres y 109 neonatos. El 28,4% de las infecciones maternas fueron en el primer trimestre, el 24,8% en el segundo y el 58,8% en el tercero. El 56% de las infecciones maternas fueron sintomáticas, solo una gestante con infección respiratoria grave ingresó en Cuidados Intensivos. La edad gestacional media de los recién nacidos fue de 39 semanas, con un peso medio de 3.232g y un perímetro craneal de 35cm. Ocho recién nacidos hijos de madre con SARS-CoV-2 requirieron ingreso en la UCI neonatal: 2 por ictericia, 2 por distrés respiratorio, uno por prematuridad moderada y 3 por otras causas no relacionadas con infección atribuible a SARS-CoV-2. Los anticuerpos tipo IgG fueron positivas en el 56,9% de los recién nacidos. De las madres infectadas durante el primer trimestre, las IgG fueron positivas en el 32,2% de los recién nacidos, en el segundo trimestre resultaron positivos el 81,5% y en el tercero, el 58,8%. Ningún neonato presentó IgM positivas. Conclusiones La infección por SARS-CoV-2 durante la gestación proporciona anticuerpos IgG a la mitad de los recién nacidos. La presencia de anticuerpos en el recién nacido es más probable cuando la infección se ha producido en el segundo trimestre de gestación (AU)

Introduction SARS-CoV-2 infection during pregnancy and its impact on the newborn were, in the first months of the pandemic, unknown. Recent studies have provided information on the clinical involvement in the newborn and its evolution. This work shows how passive immunity varies in the newborn in relation to the moment of maternal SARS-CoV-2 infection during pregnancy. Population and method Observational, prospective and longitudinal study in a third level hospital. Epidemiological and clinical data from mothers and their newborns were collected from May 2020 to June 2021. Results A total of 109 mothers and 109 neonates have been included. 28.4% of maternal infections were in the first trimester, 24.8% during the second and 58.8% in the third. 56% of maternal infections were symptomatic and only one pregnant woman with severe respiratory infection was admitted to intensive care. The mean gestational age of the newborns was 39 weeks, with a mean weight of 3232g and a head circumference of 35cm. Eight newborns born from mothers with SARS-CoV-2 required admission to the neonatal ICU: 2 due to jaundice, 2 due to respiratory distress, 1 due to moderate prematurity, and 3 due to other causes unrelated to infection attributable to SARS-CoV-2. IgG-type antibodies were positive in 56.9% of newborns. Of the mothers infected during the 1st trimester, IgG were positive in 32.2% of the newborns, in the second trimester 81.5% were positive and in the third 58.8%. No neonate had positive IgM. Conclusions SARS-CoV-2 infection during pregnancy provides IgG antibodies to half of newborns. The presence of antibodies in the newborn is more likely when the infection has occurred in the second trimester of pregnancy (AU)

Evaluation of an immunochromatographic point-of-care test for the detection of failure of transfer of passive immunity in calves.

BACKGROUND: As calves are born without circulating immunoglobulin G (IgG) they depend on transfer of passive immunity via colostrum within the first hours of life. If calves are not sufficiently supplied with high qualitative colostrum they suffer from Failure of Transfer of Passive Immunity (FTPI). The objectives of this study were to evaluate a calf-side point-of-care test to detect calves with FTPI and to evaluate the cut-offs for a positive test result. Two hundred fifty calves from 11 dairy farms (born between September 2021 and September 2022) were included, whereof 23 were excluded due to incomplete data. Twelve to 16 h post partum the farmers carried out a point-of-care test (FASTest® IgG bovine, Megacor, Austria) using a whole blood sample. Between the 3rd and the 6th day of age, all calves were physically examined and blood samples were collected to carry out further point-of-care tests using whole blood supernatant and plasma and for measuring the Brix values in serum and plasma. Brix values in serum were used as reference for the evaluation of the point-of-care test between the 3rd and the 6th day of age, as radial immunodiffusion assays could not be conducted simultaneously. RESULTS: Brix values were not normally distributed (median at 8.6% and 9.3% in serum and plasma). In this study, the cut-off values for the point-of-care tests using whole blood supernatant and plasma were at 8.3% Brix in serum. FASTest® IgG bovine shows high sensitivities of 90% and 84% and specificities of 70% and 72% for whole blood supernatant and plasma. CONCLUSIONS: Of the 227 investigated calves, 39.7% showed Brix values of < 8.4% (cut-off for FTPI) which indicates an urgent need to improve colostrum management. The results of the study suggest that the FASTest® IgG bovine is a suitable on-farm method to assess FTPI in whole blood supernatant and plasma of calves between the 3rd and the 6th day of age. However, the results also show that FASTest® IgG bovine is not adequate to test for FTPI using whole blood at 12 to 16 h post partum.

Comparison of turbidometric immunoassay, refractometry, and gamma-glutamyl transferase to radial immunodiffusion for assessment of transfer of passive immunity in high-risk beef calves.

BACKGROUND: Attainment of adequate transfer of passive immunity (TPI) is critical to health of calves; however, studies comparing available tools for measurement of TPI in individual beef animals are limited. OBJECTIVES: To report agreement between 4 tests evaluating individual TPI status in beef calves. ANIMALS: One hundred ninety-six beef calves born to cows and heifers presenting for calving management or dystocia. METHODS: Retrospective study to assess serum immunoglobulin (IgG) concentrations via turbidimetric immunoassay (TI), gamma-glutamyl transferase (GGT), serum total protein (TP), and single radial immunodiffusion (RID; reference standard). Test agreement was evaluated using Passing-Bablok regression, Bland-Altman analysis, Cohen's kappa, and receiver operating characteristic (ROC) curves with and without covariate adjustment to determine optimal thresholds. RESULTS: Correlation between RID and test results varied: TI, ρ = 0.757; TP, ρ = 0.715; GGT: ρ = 0.413. For the TI compared to RID, regression analysis identified a constant (intercept = -0.51 [CI: -2.63, 3.05]) and proportional (slope = 1.87 [CI: 1.69, 2.08]) bias. Based on ROC, TI concentrations of ≤9.89 and ≤13.76 g/L, and TP concentrations of ≤5.5 and ≤6.0 g/dL, indicated IgG concentrations <18.0 and <25.0 g/L, respectively. CONCLUSIONS AND CLINICAL IMPORTANCE: Within this cohort of calves, TI demonstrated the best correlation with RID; however, significant bias was identified which led to frequent underestimation of IgG concentration. Serum total protein demonstrated less correlation with RID but had less misclassification than TI. Both TI and TP demonstrated less correlation for calves that received colostrum replacement prompting clinical awareness of colostrum type when evaluating individual TPI in beef calves.

Transfer of naturally acquired specific passive immunity against Anaplasma phagocytophilum in foals in Southeastern Pennsylvania and Northern Maryland.

BACKGROUND: Equine granulocytic anaplasmosis (EGA) is a common disease in adult horses, but clinical disease in foals is rarely reported. The relationship between equine maternal and neonatal antibodies to Anaplasma phagocytophilum is unclear. HYPOTHESIS/OBJECTIVES: That mares in an endemic region would be seropositive for A. phagocytophilum and that mare and foal serum IgG concentrations for A. phagocytophilum would correlate. Additionally, we hypothesized that foal IgG concentrations for A. phagocytophilum acquired by passive immunity would decline by 6 months of age. ANIMALS: Twenty-two healthy mare-foal pairs. METHODS: This prospective observational study investigated serum IgG concentrations specific for A. phagocytophilum in mares and foals using an immunofluorescent antibody test (IFA). The association between foal titer (as a binary variable) and age in months was assessed using a mixed-effects logistic regression. RESULTS: A positive correlation between newborn foal antibody titers and mare titers was identified at both the pre-foaling (τa = 0.38, τb = 0.50, P = .009) and foaling timepoints (τa = 0.36, τb = 0.47, P = .01). In A. phagocytophilum seropositive neonates, it was unlikely that a positive titer would be detected by 3 months of age (OR = 0.002, P = .02, 95% CI: 0.00001-0.38). Three out of 20 foals seroconverted between 3 and 6 months of age. CONCLUSIONS AND CLINICAL IMPORTANCE: Transfer of specific passive immunity to A. phagocytophilum occurred in 80% of foals born to seropositive mares and declined by 3 months of age. A. phagocytophilum infection should be considered in foals displaying clinical signs consistent with EGA.

Potential for Maternally Administered Vaccine for Infant Group B Streptococcus.

BACKGROUND: Natural history studies have correlated serotype-specific anti-capsular polysaccharide (CPS) IgG in newborns with a reduced risk of group B streptococcal disease. A hexavalent CPS-cross-reactive material 197 glycoconjugate vaccine (GBS6) is being developed as a maternal vaccine to prevent invasive group B streptococcus in young infants. METHODS: In an ongoing phase 2, placebo-controlled trial involving pregnant women, we assessed the safety and immunogenicity of a single dose of various GBS6 formulations and analyzed maternally transferred anti-CPS antibodies. In a parallel seroepidemiologic study that was conducted in the same population, we assessed serotype-specific anti-CPS IgG concentrations that were associated with a reduced risk of invasive disease among newborns through 89 days of age to define putative protective thresholds. RESULTS: Naturally acquired anti-CPS IgG concentrations were associated with a reduced risk of disease among infants in the seroepidemiologic study. IgG thresholds that were determined to be associated with 75 to 95% reductions in the risk of disease were 0.184 to 0.827 µg per milliliter. No GBS6-associated safety signals were observed among the mothers or infants. The incidence of adverse events and of serious adverse events were similar across the trial groups for both mothers and infants; more local reactions were observed in the groups that received GBS6 containing aluminum phosphate. Among the infants, the most common serious adverse events were minor congenital anomalies (umbilical hernia and congenital dermal melanocytosis). GBS6 induced maternal antibody responses to all serotypes, with maternal-to-infant antibody ratios of approximately 0.4 to 1.3, depending on the dose. The percentage of infants with anti-CPS IgG concentrations above 0.184 µg per milliliter varied according to serotype and formulation, with 57 to 97% of the infants having a seroresponse to the most immunogenic formulation. CONCLUSIONS: GBS6 elicited anti-CPS antibodies against group B streptococcus in pregnant women that were transferred to infants at levels associated with a reduced risk of invasive group B streptococcal disease. (Funded by Pfizer and the Bill and Melinda Gates Foundation; C1091002 ClinicalTrials.gov number, NCT03765073.).

Assessing failure of transfer of passive immunity by gamma-glutamyl-transferase activity and serum refractometry in holstein-friesian calves affected by neonatal diarrhea.

Hardly published data are available to diagnose the failure of transfer of passive immunity (FTPI) in calves affected by neonatal calf diarrhea (NCD). This study evaluated the diagnostic performance and differences among optical serum total protein (STP) concentration and gamma-glutamyl-transferase (GGT) activity for assessing FTPI in diarrheic Holstein Friesian calves. 72 diarrheic and 19 healthy Holstein Friesian calves aged 1 to 10 days were enrolled. Each calf underwent a complete clinical examination and dehydration assessment. The effect of dehydration status and age on the correlation between the two methods under study (STP and GGT) and the gold standard (Immunoglobulin G [IgG] measured with RID) was investigated with Spearman's correlation index R for ranks. Serum total protein concentration and GGT activity were analyzed by receiver operating characteristic (ROC) curve analysis to identify the optimal cut-off point to distinguish between diarrheic calves with or without FTPI, also considering the effects of dehydration and age. The results show that GGT activity was affected by the age of calves, while STP was influenced by dehydration. The cut-offs to distinguish calves with IgG < 10 g/L were < 52 g/L of STP in normohydrated calves, < 58 g/L of STP in dehydrated calves, and < 124 IU/L of GGT in calves with aged between 3 and 10 days. In nondehydrated diarrheic calves, the STP refractometer showed better diagnostic accuracy.In dehydrated calves aged between 3 and 10 days, however, its accuracy drops, and it is advisable to use GGT activity.

Influence of Timing of Maternal Pertussis Immunization on the Avidity of Transferred Antibodies in Term and Preterm Neonates.

The timing of maternal pertussis vaccination influences the titers of cord-blood anti-pertussis antibodies. Whether it affects their avidity is unknown. We demonstrate in 298 term and 72 preterm neonates that antibody avidity is independent of the timing of maternal vaccination, whether comparing second with third trimester or intervals before birth.

Diagnostic accuracy of refractometry methods for estimating passive immunity status in neonatal beef calves.

BACKGROUND: Assessing the inadequate transfer of passive immunity (ITPI) in beef calves is crucial because calves with ITPI are at high risk for morbidity and mortality. OBJECTIVES: The aim of this study was to determine the accuracy of digital Brix (D-BRIX) and digital serum total protein (D-STP) refractometers to estimate different passive immunity status in beef calves and to determine the robustness of thresholds. METHODS: Blood samples were collected from 202 (1-7 days old) beef calves. Serum total solid percentages, total protein concentrations, and IgG concentrations were measured with the D-BRIX refractometer, D-STP refractometer, and gold standard radial immunodiffusion (RID) assay, respectively. Data were analyzed using diagnostic test accuracy, areas under the receiver operating characteristics curve, Cohen's kappa coefficient, and misclassification costs analysis to estimate IgG concentrations <10, <16, and <24 mg/mL. RESULTS: For the prediction of serum IgG concentrations <10, <16 and <24 mg/mL, the optimal cut-off values were determined to be <8.5% (Se: 100.0% (95% CI: 87.9-100.0); Sp: 94.2% [95% CI: 89.6-97.2]), <8.5% (Se: 92.1% [95% CI: 78.6-98.2]; Sp: 97.6% [95% CI: 93.9-99.3]), and <10.1% (Se: 88.8% [95% CI: 79.7-94.7]; Sp: 67.2% [95% CI: 58.1-75.4]), respectively, for the D-BRIX refractometer; and <5.2 g/dL (Se: 100.0% [95% CI: 87.9-100.0]; Sp: 93.6% [95% CI: 88.9-96.8]), <5.2 g/dL (Se: 92.1% [95% CI: 78.6-98.2]; Sp: 97.0% [95% CI: 93.0-99.0]), and <6.4 g/dL (Se: 87.5% [95% CI: 78.2-93.8]; Sp: 69.7% [95% CI: 60.7-77.7]), respectively, for the D-STP refractometer. CONCLUSIONS: The digital Brix and digital serum total protein refractometers can be used as monitoring tools for assessing passive immunity transfer in neonatal beef calves.

Sources of variance in the results of a commercial bovine immunoglobulin G radial immunodiffusion assay.

Radial immunodiffusion (RID) is used to quantify IgG concentration in neonatal beef or dairy calf serum; variability has been noted that may affect the precision and accuracy of assay results. We determined the source, range, and homogeneity of variance in the results of a commercial bovine IgG RID assay (Triple J Farm). To estimate the variance in the precipitin ring diameter, we used 6 sera, measured 28 times across 8 plates and 4 lots, and 3 standards with known IgG concentrations, measured 75 times across 69 plates and 5 lots. The source of diameter variance was determined using variance partition coefficients for lot, plate, and repetition. We used 11 different methods to generate standard curves to convert RID precipitin ring diameters to IgG concentrations. The Levene test of homogeneity of variance (α = 0.1) was used to evaluate the equality of variance between the standards or serum precipitin ring diameters and calculated IgG concentrations. Lot and plate contributed minimally to the diameter variance. Precipitin ring diameters had equal variance. Calculated IgG concentrations for serum not requiring dilution had equal variance. A linear equation from aggregated standards, performed within the same day, had greater accuracy for the calculated IgG concentrations of the standards compared to other equation methods. Regardless of standard curve methodology or IgG concentration, variability inherent to the assay limits its clinical usefulness.

Transplacental transfer of total immunoglobulin G and antibodies to Plasmodium falciparum antigens between the 24th week of gestation and term.

Full-term newborns have antibody (Ab) repertoires and levels similar to their mothers to help protect them from environmental pathogens. Unfortunately, preterm babies, especially those born < 34 weeks, have reduced levels of protective antibodies. In Africa, antibodies to Plasmodium falciparum are important in protection from malaria. This study investigated the transfer of total IgG and antibodies to 9 P. falciparum antigens and tetanus toxoid between 24 weeks and term. Paired maternal and cord samples from 166 preterm (24-37 weeks) and 154 term deliveries were used. Transfer efficiency was expressed as the ratio of Ab levels in cord to maternal plasma (CMR). At 24-25 weeks, CMR ranged from 0.31 to 0.94 for the different antigens; the rate of transfer was similar for all antigens between 24 and 40 weeks; resulting in median CMR of 0.49-0.95 at term. Babies of mothers with hypergammaglobulinemia and normal IgG levels had similar amounts of IgG, supporting data that saturation of the neonatal Fc-receptor occurs at ~ 16 mg IgG/ml. Thus, babies born prior to 34-35 weeks in Africa are likely to have reduced Ab levels to some, but not all antigens. Since IgG transfer is Fc-mediated, why differences exist in CMR among the antigens warrants further investigation.

Waning of maternal antibody against measles virus in Shufu, China.

BACKGROUND: As measles vaccination coverage has increased, measles infection has shifted to the population of infants. We conducted a follow-up seroepidemiological study among mothers and their infants to evaluate measles seroprevalence and the persistence of maternal measles antibody in Shufu, Kashgar from 2018 to 2020. METHODS: Maternal venous blood and cord blood was obtained among mothers and their infants at 0, 3, 5, 8, 9, and 12 months of age. An enzyme-linked immunosorbent assay was used for quantitative measurement of measles antibodies. We analyzed the correlation between maternal and neonatal measles antibodies, and antibodies persistence after infants were born. RESULTS: The overall neonatal maternal ratio was 2.38 (95%CI: 2.05-2.71). The measles antibodies for mothers and newborns were 438.93 IU/mL (95%CI: 409.47-470.51 IU/mL) and 440.10 IU/mL (95%CI: 410.82-471.48 IU/mL), respectively. Neonatal measles antibodies were dropping after birth and then beginning to increase starting at 8 months of age. CONCLUSIONS: Infant measles antibody levels progressively declined after birth regardless of maternal measles antibody levels. Efforts should be carried out to eliminate measles.

Evaluation of 2 refractometers to estimate different passive immunity status in Simmental dairy calves.

Inadequate transfer of passive immunity (ITPI) is major risk for mortality, morbidity and decreased growth performance in dairy and beef calves. Refractometry method is used in estimating ITPI in dairy and beef calves but studies evaluating refractometers for Simmental dairy calves are limited. The objectives of this study were determining the accuracy of digital serum total protein refractometer (STP-REF) and digital Brix refractometer (BRIX-REF) in the estimating of different passive immunity status (<10, <18, <25 and <32 g/L) in Simmental dairy calves. Serum samples were collected from apparently healthy Simmental dairy calves aged 1-8 days (n = 291). Serum total solid percentages were measured using BRIX-REF, serum total protein concentrations were measured using STP-REF and serum IgG concentrations were measured using radial immunodiffusion (RID) assay as a reference test. Correlation coefficients were calculated between RID test and refractometers results, and each other. The diagnostic test performance of the refractometers at IgG concentrations of < 10, < 18, < 25 and < 32 g/L was measured by performing a receiver operating characteristics (ROC) analysis. The optimal thresholds of the refractometers were determined based on Youden's J statistics and after accounting for different costs between false positive and false negative cases using misclassification cost term analysis. The overall test performance and the agreement of the refractometers were assessed using area under the ROC curve and Cohen's kappa analysis. Optimal thresholds were determined as < 7.9, < 8.3, < 8.7, < 9.4% for the BRIX-REF, and < 4.6, < 5.2, < 5.4, < 5.8 g/dL for the STP-REF in estimating IgG concentrations of < 10, < 18, < 25, < 32 g/L, respectively. Se and Sp of BRIX-REF were 88.8% and 89.1% for < 7.9% Brix, 81.6% and 94.2% for < 8.3% Brix, 77.9% and 97.4% for < 8.7% Brix and 81.7% and 91.2% for < 9.4% Brix, respectively. Se and Sp of STP-REF 92.5% and 88.2% for < 4.6 g/dL; 92.1% and 87.1% for < 5.2 g/dL; 81.7% and 93.6% for < 5.4 g/dL; 79.0% and 94.1% for < 5.8 g/dL, respectively. Both, digital Brix and STP refractometers performed well to estimate the status of passive immunity in dairy Simmental calves.

Effect of Plasmodium Infection during Pregnancy on Passive Neonatal Immunity against Tetanus Toxoid and Rotavirus.

Passive immunity acquired through transplacental IgG transport is essential to protect infants against pathogens as childhood vaccination programs begins. Diarrhea caused by rotavirus and neonatal tetanus are common and potentially fatal childhood infections that can be prevented by transplacental IgG. However, it is not known whether maternal infections in pregnancy can reduce the transfer of these antibodies to the fetus. This study evaluated the effect of submicroscopic Plasmodium infection during pregnancy on the transfer of maternal IgG antibodies against rotavirus (anti-RV) and tetanus toxoid (anti-TT) to newborns of pregnant women residing in Puerto Libertador and Tierralta, Colombia. Expression of different immune mediators and levels of IgG against rotavirus and tetanus toxoid were quantified in pregnant women with and without Plasmodium infection during pregnancy. Submicroscopic infection at the time of delivery was associated with a cord-to-maternal ratio (CMR) > 1 for anti-RV and < 1 for anti-TT IgG, as well as with an increase in the expression of immune mediators of inflammation (IFN-γ), anti-inflammation (IL-10, TGF-ß), and regulation (FoxP3, CTLA-4). When compared by species, these findings (CMR > 1 for anti-RV and < 1 for anti-TT IgG) were conserved in submicroscopic Plasmodium vivax infections at delivery. The impact of Plasmodium infections on neonatal susceptibility to other infections warrants further exploration.

Bayesian latent class analysis of the characteristics of diagnostic tests to assess the passive immunity transfer status in neonatal Belgian Blue beef calves.

The aim of the current study was to assess the diagnostic characteristics of radial immunodiffusion (RID), capillary electrophoresis (CE) and digital brix refractometry (Bx) for the diagnosis of failure of passive transfer (FPT) of immunity in neonatal Belgian Blue beef calves in the absence of a gold standard using a Bayesian latent class model. Belgian blue beef calves (n = 202) from a large farm in the south of Belgium were blood-sampled at 48-72 h of age and tested for FPT. The true prevalence of FPT in this population of calves was 34.5 % (95 % BCI: 26.1-44.3) using a FPT cut-off point of 10 g IgG/L. This true prevalence increased to 66.3 (95 % BCI: 56.9-74.8) and 88.9 % (95 % BCI: 83.1-93.2) at FPT cut-off points of respectively 18 and 25 g IgG/L serum. The Bland-Altman plot comparing the RID and CE methods, revealed that the serum IgG concentrations obtained by RID were on average 2.25 (95 % CI 1.62-2.88) g/L higher than those measured by CE. Optimal cut-off values for CE, corresponding to the FPT values as measured by RID of 10, 18, and 25 g IgG/L serum, were respectively 10, 15, and 20 g IgG/L. The overall diagnostic accuracy of the three diagnostic tests was comparable at the FPT cut-off point of 10 g IgG/L serum (i.e. 85 %). At higher cut-off points for FPT, the RID and CE assays presumably performed better that the Bx method. In conclusion, we demonstrated that: (1) the CE method is a good alternative for the RID assay, the latter having important constraints when considering its practicality, and (2) the Bx method is a cheap and user-friendly indirect method to evaluate the FPT in new-born Belgian Blue beef calves.

Diagnostic accuracy of digital Brix and serum total protein refractometers in estimating different passive immunity levels in dairy calves.

The aim of this study was to determine the diagnostic accuracy of digital serum total protein (TP) and digital Brix refractometers in estimating different passive immunity levels (<10, <18, <25 mg/mL) in dairy calves. Blood samples were collected from 260 apparently healthy Holstein calves, aged 2-7 days. Serum IgG concentrations were measured using digital Brix and TP refractometers and the radial immunodiffusion (RID) assay, as the gold standard. Data were analyzed by a receiver operating characteristics (ROC) analysis, the area under the ROC curves (AUC) and Cohen's kappa (κ). Optimal thresholds were determined as < 8.4, < 9.0 and < 9.4% for the digital Brix refractometer, and < 5.0, < 5.4 and < 5.8 g/dL for the serum TP refractometer in estimating IgG concentrations of < 10, < 18, < 25 mg/mL, respectively. The sensitivity (Se) and specificity (Sp) of the Brix refractometer were 96.3% and 88.8% for < 8.4% Brix, 97.0% and 83.4% for < 9.0% Brix, and 85.5% and 77.8% for < 9.4% Brix, respectively. The Se and Sp of the serum TP refractometer were 96.3% and 90.1% for < 5.0 g/dL, 91.0% and 89.6% for < 5.4 g/dL, 79.6% and 85.2% for < 5.8 g/dL, respectively. The discriminant ability of the refractometers was moderately accurate in estimating IgG concentrations of < 10 and < 18 mg/mL, and highly accurate in estimating IgG concentrations of < 25 mg/mL. Both refractometers substantially agreed with RID-IgG results and almost perfectly agreed with each other. In conclusion, the digital Brix and digital serum TP refractometers offer a good utility for determining different passive immunity levels in dairy calves.

HIV-Associated Alterations of the Biophysical Features of Maternal Antibodies Correlate With Their Reduced Transfer Across the Placenta.

BACKGROUND: Human immunodeficiency virus (HIV) infection during pregnancy is associated with reduced transplacental transfer of maternal antibodies and increased risk of severe infections in children who are exposed and uninfected with HIV. The basis of this reduced transfer of maternal immunity has not yet been defined but could involve modifications in the biophysical features of antibodies. The objective of this study was to assess the impact of maternal HIV infection on the biophysical features of serum IgG and transplacental antibody transfer. METHODS: Maternal serum IgG subclass levels, Fc glycosylation, Fc receptor (FcR) binding, and transplacental transfer of pathogen-specific maternal IgG were measured in pregnant women with HIV (WWH) and pregnant women testing negative for HIV (WNH) in Cape Town, South Africa. RESULTS: Maternal antibody profiles were strikingly different between pregnant WWH and WNH. Antibody binding to FcγR2a and FcγR2b, IgG1 and IgG3 antibodies, and agalactosylated antibodies were all elevated in WWH, whereas digalactosylated and sialylated antibodies were reduced compared to pregnant WNH. Antibody features that were elevated in WWH were also correlated with reduced transplacental transfer of vaccine antigen-specific antibodies. CONCLUSIONS: HIV infection is associated with marked alterations of biophysical features of maternal IgG and reduced placental transfer, potentially impairing antimicrobial immunity.

Pregnancy enables antibody protection against intracellular infection.

Adaptive immune components are thought to exert non-overlapping roles in antimicrobial host defence, with antibodies targeting pathogens in the extracellular environment and T cells eliminating infection inside cells1,2. Reliance on antibodies for vertically transferred immunity from mothers to babies may explain neonatal susceptibility to intracellular infections3,4. Here we show that pregnancy-induced post-translational antibody modification enables protection against the prototypical intracellular pathogen Listeria monocytogenes. Infection susceptibility was reversed in neonatal mice born to preconceptually primed mothers possessing L. monocytogenes-specific IgG or after passive transfer of antibodies from primed pregnant, but not virgin, mice. Although maternal B cells were essential for producing IgGs that mediate vertically transferred protection, they were dispensable for antibody acquisition of protective function, which instead required sialic acid acetyl esterase5 to deacetylate terminal sialic acid residues on IgG variable-region N-linked glycans. Deacetylated L. monocytogenes-specific IgG protected neonates through the sialic acid receptor CD226,7, which suppressed IL-10 production by B cells leading to antibody-mediated protection. Consideration of the maternal-fetal dyad as a joined immunological unit reveals protective roles for antibodies against intracellular infection and fine-tuned adaptations to enhance host defence during pregnancy and early life.