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.

Assessment of Maternal and Neonatal SARS-CoV-2 Viral Load, Transplacental Antibody Transfer, and Placental Pathology in Pregnancies During the COVID-19 Pandemic.

Importance: Biological data are lacking with respect to risk of vertical transmission and mechanisms of fetoplacental protection in maternal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Objective: To quantify SARS-CoV-2 viral load in maternal and neonatal biofluids, transplacental passage of anti-SARS-CoV-2 antibody, and incidence of fetoplacental infection. Design, Setting, and Participants: This cohort study was conducted among pregnant women presenting for care at 3 tertiary care centers in Boston, Massachusetts. Women with reverse transcription-polymerase chain reaction (RT-PCR) results positive for SARS-CoV-2 were recruited from April 2 to June 13, 2020, and follow-up occurred through July 10, 2020. Contemporaneous participants without SARS-CoV-2 infection were enrolled as a convenience sample from pregnant women with RT-PCR results negative for SARS-CoV-2. Exposures: SARS-CoV-2 infection in pregnancy, defined by nasopharyngeal swab RT-PCR. Main Outcomes and Measures: The main outcomes were SARS-CoV-2 viral load in maternal plasma or respiratory fluids and umbilical cord plasma, quantification of anti-SARS-CoV-2 antibodies in maternal and cord plasma, and presence of SARS-CoV-2 RNA in the placenta. Results: Among 127 pregnant women enrolled, 64 with RT-PCR results positive for SARS-CoV-2 (mean [SD] age, 31.6 [5.6] years) and 63 with RT-PCR results negative for SARS-CoV-2 (mean [SD] age, 33.9 [5.4] years) provided samples for analysis. Of women with SARS-CoV-2 infection, 23 (36%) were asymptomatic, 22 (34%) had mild disease, 7 (11%) had moderate disease, 10 (16%) had severe disease, and 2 (3%) had critical disease. In viral load analyses among 107 women, there was no detectable viremia in maternal or cord blood and no evidence of vertical transmission. Among 77 neonates tested in whom SARS-CoV-2 antibodies were quantified in cord blood, 1 had detectable immunoglobuilin M to nucleocapsid. Among 88 placentas tested, SARS-CoV-2 RNA was not detected in any. In antibody analyses among 37 women with SARS-CoV-2 infection, anti-receptor binding domain immunoglobin G was detected in 24 women (65%) and anti-nucleocapsid was detected in 26 women (70%). Mother-to-neonate transfer of anti-SARS-CoV-2 antibodies was significantly lower than transfer of anti-influenza hemagglutinin A antibodies (mean [SD] cord-to-maternal ratio: anti-receptor binding domain immunoglobin G, 0.72 [0.57]; anti-nucleocapsid, 0.74 [0.44]; anti-influenza, 1.44 [0.80]; P < .001). Nonoverlapping placental expression of SARS-CoV-2 receptors angiotensin-converting enzyme 2 and transmembrane serine protease 2 was noted. Conclusions and Relevance: In this cohort study, there was no evidence of placental infection or definitive vertical transmission of SARS-CoV-2. Transplacental transfer of anti-SARS-CoV-2 antibodies was inefficient. Lack of viremia and reduced coexpression and colocalization of placental angiotensin-converting enzyme 2 and transmembrane serine protease 2 may serve as protective mechanisms against vertical transmission.

Assessment of the immunocrit method to detect failure of passive immunity in newborn foals.

BACKGROUND: In newborn foals the absorption of colostrum immunoglobulins in the small intestine is maximal up to 8 hours after birth and then progressively decreases to become null after 24 hours post-partum. Thus, equine practitioners need a simple, quick, inexpensive and reliable field test to identify foals affected by failure of passive transfer rather than an accurate method yielding quantitative results within the whole range of immunoglobulin concentrations. OBJECTIVE: As the validity of the immunocrit method to detect failure of passive transfer in foals had not been evaluated before, the objective of this study was to test the ability of this method to detect the concentration of immunoglobulins in a large number of foal serum samples. STUDY DESIGN: Assay validation using samples collected for clinical purposes. METHODS: The immunocrit test, using a 40% ammonium sulphate solution, was used to measure the concentration of immunoglobulins in serum samples from 211 newborn Thoroughbred foals. The results were compared, by statistical analysis, with those of agarose gel electrophoresis, a reference quantitative method. RESULTS: The values obtained by the immunocrit method were significantly correlated (R = .871; P < .001) with those measured by agarose gel electrophoresis. A cut-off value of 8 g/L of serum immunoglobulins by agarose gel electrophoresis and its equivalent of 9.5% for the immunocrit test was indicative of failure of passive transfer. The sensitivity and specificity of the immunocrit method at this cut-off point were 94% (95% CI, 90-97.3) and 82% (95% CI, 72.13-91.8) respectively. MAIN LIMITATIONS: Variable times of sample extraction after colostrum suckling, over the study period. CONCLUSIONS: The immunocrit test provides a quantitative, quick, inexpensive, reliable and objective method to detect failure of passive transfer of maternal immunity in newborn foals, which is easy to perform directly in horse farms, with minimum laboratory equipment.

The Impact of Early Postpartum Maternal Pertussis Vaccination on the Protection of Infants: A Randomized Clinical Trial.

BACKGROUND: Despite primary vaccination, infants under six months run a risk of infection with pertussis. OBJECTIVE: To determine the impact of early postpartum maternal pertussis vaccination on protecting infants from the disease. METHODS: All mothers (n=405) who gave birth to healthy term infants were educated on the cocoon strategy. The mothers who consented were immunized with the tetanus-diphtheria-acellular pertussis vaccine within the first three postpartum days. All infants received their pertussis vaccines according to the national schedule. The anti-pertussis IgG titers of infants of thirty vaccinated mothers were compared with those of thirty unvaccinated mothers. RESULTS: The pertussis antibody levels in the infants of vaccinated mothers were significantly higher than those of unvaccinated mothers at the mean infant age of 5.6 ± 1.2 months. Only 6 infants of vaccinated mothers exhibited pertussis-like symptoms, none of whom had positive pertussis PCR. Seventeen infants of unvaccinated mothers had pertussis-like symptoms, and 4 tested positive for pertussis PCR. CONCLUSION: Our results showed that maternal pertussis vaccination, administered within the first three postpartum days, may protect infants against pertussis in their first ten months.

A Mouse Model of Enterovirus D68 Infection for Assessment of the Efficacy of Inactivated Vaccine.

In recent years, enterovirus D68 (EVD68) has been reported increasingly to be associated with severe respiratory tract infections and acute flaccid myelitis (AFM) in children all over the world. Yet, no effective vaccines or antiviral drugs are currently available for EVD68. Although several experimental animal models have been developed, immunogenicity and protective efficacy of inactivated EVD68 vaccines has not been fully evaluated. To promote the development of vaccines, we established an Institute of Cancer Research (ICR) suckling mouse model of EVD68 infection in this study. The results showed that ICR neonatal mice up to about nine days of age were susceptible to infection with EVD68 clinical strain US/MO/14-18947 by intraperitoneal injection. The infected mice exhibited progressive limb paralysis prior to death and the mortality of mice was age- and virus dose-dependent. Tissue viral load analysis showed that limb muscle and spinal cord were the major sites of viral replication. Moreover, histopathologic examination revealed the severe necrosis of the limb and juxtaspinal muscles, suggesting that US/MO/14-18947 has a strong tropism toward muscle tissues. Additionally, ß-propiolactone-inactivated EVD68 vaccine showed high purity and quality and induced robust EVD68-specific neutralizing antibody responses in adult mice. Importantly, results from both antisera transfer and maternal immunization experiments clearly showed that inactivated EVD68 vaccine was able to protect against lethal viral infection in the mouse model. In short, these results demonstrate the successful establishment of the mouse model of EVD68 infection for evaluating candidate vaccines against EVD68 and also provide important information for the development of inactivated virus-based EVD68 vaccines.

Trans-generational immune priming in the mealworm beetle protects eggs through pathogen-dependent mechanisms imposing no immediate fitness cost for the offspring.

Immune-challenged mothers can improve their offspring immunity through trans-generational immune priming (TGIP). In insects, TGIP endows the offspring with lifetime immunity, including the eggs, which are likely exposed soon after maternal infection. Egg protection may rely on the transfer of maternal immune effectors to the egg or/and the induction of egg immune genes. These respective mechanisms are assumed to have early-life fitness costs of different magnitude for the offspring. We provide evidence in the mealworm beetle Tenebrio molitor that enhanced egg immunity following a maternal immune challenge is achieved by both of these mechanisms but in a pathogen-dependent manner. While previously found having late-life fitness costs for the offspring, TGIP here improved egg hatching success and early larval survival, in addition of improving offspring immunity. These results suggest that early-life of primed offspring is critical in the optimization of life history trajectory of this insect under trans-generational pathogenic threats.

Rotavirus specific maternal antibodies and immune response to RV3-BB neonatal rotavirus vaccine in New Zealand.

BACKGROUND: Maternal antibodies, acquired passively via placenta and/or breast milk, may contribute to the reduced efficacy of oral rotavirus vaccines observed in children in developing countries. This study aimed to investigate the effect of rotavirus specific maternal antibodies on the serum IgA response or stool excretion of vaccine virus after any dose of an oral rotavirus vaccine, RV3-BB, in parallel to a Phase IIa clinical trial conducted at Dunedin Hospital, New Zealand. At the time of the study rotavirus vaccines had not been introduced in New Zealand and the burden of rotavirus disease was evident. METHODS: Rotavirus specific IgG and serum neutralizing antibody (SNA) levels in cord blood and IgA levels in colostrum and breast milk samples collected ∼4 weeks, ∼20 weeks and ∼28 weeks after birth were measured. Infants were randomized to receive the first dose of vaccine at 0-5 d (neonatal schedule) or 8 weeks (infant schedule). Breast feeding was with-held for 30 minutes before and after vaccine administration. The relationship between rotavirus specific IgG and SNA levels in cord blood and IgA in colostrum and breast milk at the time of first active dose of RV3-BB vaccine and level of IgA response and stool excretion after 3 doses of vaccine was assessed using linear and logistic regression. RESULTS: Forty infants received 3 doses of RV3-BB rotavirus vaccine and were included in the analysis of the neonatal and infant groups. Rotavirus specific IgA in colostrum (neonatal schedule group) and breast milk at 4 weeks (infant schedule group) was identified in 14/21 (67%) and 14/17 (82%) of infants respectively. There was little evidence of an association between IgA in colostrum or breast milk IgA at 4 weeks, or between cord IgG or SNA level, and IgA response or stool excretion after 3 doses of RV3-BB, or after one dose (neonatal schedule) (all p>0.05). CONCLUSIONS: The level of IgA in colostrum or breast milk and level of placental IgG and SNA did not impact on the serum IgA response or stool excretion following 3 doses of RV3-BB Rotavirus Vaccine administered using either a neonatal or infant schedule in New Zealand infants.

Assessing the Evidence for Maternal Pertussis Immunization: A Report From the Bill & Melinda Gates Foundation Symposium on Pertussis Infant Disease Burden in Low- and Lower-Middle-Income Countries.

Implementation of effective interventions has halved maternal and child mortality over the past 2 decades, but less progress has been made in reducing neonatal mortality. Almost 45% of under-5 global mortality now occurs in infants <1 month of age, with approximately 86% of neonatal deaths occurring in low- and lower-middle-income countries (LMICs). As an estimated 23% of neonatal deaths globally are due to infectious causes, maternal immunization (MI) is one intervention that may reduce mortality in the first few months of life, when direct protection often relies on passively transmitted maternal antibodies. Despite all countries including pertussis-containing vaccines in their routine childhood immunization schedules, supported through the Expanded Programme on Immunization, pertussis continues to circulate globally. Although based on limited robust epidemiologic data, current estimates derived from modeling implicate pertussis in 1% of under-5 mortality, with infants too young to be vaccinated at highest risk of death. Pertussis MI programs have proven effective in reducing infant pertussis mortality in high-income countries using tetanus-diphtheria-acellular pertussis (Tdap) vaccines in their maternal and infant programs; however, these vaccines are cost-prohibitive for routine use in LMICs. The reach of antenatal care programs to deliver maternal pertussis vaccines, particularly with respect to infants at greatest risk of pertussis, needs to be further evaluated. Recognizing that decisions on the potential impact of pertussis MI in LMICs need, as a first step, robust contemporary mortality data for early infant pertussis, a symposium of global key experts was held. The symposium reviewed current evidence and identified knowledge gaps with respect to the infant pertussis disease burden in LMICs, and discussed proposed strategies to assess the potential impact of pertussis MI.

Failure of Passive Immune Transfer in Calves: A Meta-Analysis on the Consequences and Assessment of the Economic Impact.

Low colostrum intake at birth results in the failure of passive transfer (FPT) due to the inadequate ingestion of colostral immunoglobulins (Ig). FPT is associated with an increased risk of mortality and decreased health and longevity. Despite the known management practices associated with low FPT, it remains an important issue in the field. Neither a quantitative analysis of FPT consequences nor an assessment of its total cost are available. To address this point, a meta-analysis on the adjusted associations between FPT and its outcomes was first performed. Then, the total costs of FPT in European systems were calculated using a stochastic method with adjusted values as the input parameters. The adjusted risks (and 95% confidence intervals) for mortality, bovine respiratory disease, diarrhoea and overall morbidity in the case of FPT were 2.12 (1.43-3.13), 1.75 (1.50-2.03), 1.51 (1.05-2.17) and 1.91 (1.63-2.24), respectively. The mean (and 95% prediction interval) total costs per calf with FPT were estimated to be €60 (€10-109) and €80 (€20-139) for dairy and beef, respectively. As a result of the double-step stochastic method, the proposed economic estimation constitutes the first estimate available for FPT. The results are presented in a way that facilitates their use in the field and, with limited effort, combines the cost of each contributor to increase the applicability of the economic assessment to the situations farm-advisors may face. The present economic estimates are also an important tool to evaluate the profitability of measures that aim to improve colostrum intake and FPT prevention.

Cost-effectiveness analysis of universal maternal immunization with tetanus-diphtheria-acellular pertussis (Tdap) vaccine in Brazil.

BACKGROUND: Pertussis incidence has increased significantly in Brazil since 2011, despite high coverage of whole-cell pertussis containing vaccines in childhood. Infants <4 months are most affected. This study aimed to evaluate the cost-effectiveness of introducing universal maternal vaccination with tetanus-diphtheria-acellular pertussis vaccine (Tdap) into the National Immunization Program in Brazil. METHODS: Economic evaluation using a decision tree model comparing two strategies: (1) universal vaccination with one dose of Tdap in the third trimester of pregnancy and (2) current practice (no pertussis maternal vaccination), from the perspective of the health system and society. An annual cohort of newborns representing the number of vaccinated pregnant women were followed for one year. Vaccine efficacy were based on literature review. Epidemiological, healthcare resource utilization and cost estimates were based on local data retrieved from Brazilian Health Information Systems. Costs of epidemiological investigation and treatment of contacts of cases were included in the analysis. No discount rate was applied to costs and benefits, as the temporal horizon was one year. Primary outcome was cost per life year saved (LYS). Univariate and best- and worst-case scenarios sensitivity analysis were performed. RESULTS: Maternal vaccination of one annual cohort, with vaccine effectiveness of 78%, and vaccine cost of USD$12.39 per dose, would avoid 661 cases and 24 infant deaths of pertussis, save 1800 years of life and cost USD$28,942,808 and USD$29,002,947, respectively, from the health system and societal perspective. The universal immunization would result in ICERs of USD$15,608 and USD$15,590 per LYS, from the health system and societal perspective, respectively. In sensitivity analysis, the ICER was most sensitive to discounting of life years saved, variation in case-fatality, disease incidence, vaccine cost, and vaccine effectiveness. CONCLUSION: The results indicate that universal maternal immunization with Tdap is a cost-effective intervention for preventing pertussis cases and deaths in infants in Brazil.

Correlation of serum IgG concentration in foals and refractometry index of the dam's pre- and post-parturient colostrums: an assessment for failure of passive transfer in foals.

The object of this study was to evaluate the usefulness of measuring the differences in the values of the serum total protein (DVSTP) concentration of foals and the refractometry index (DVRI) of the milk of dams before and after nursing of the colostrum for assessing failure of passive transfer (FPT) in foals. Serum samples from 31 foals were collected before the first nursing and other 1 to 6 times between 4 and 24 hr after birth. Paired colostrum and milk samples were collected from 14 of their dams at the same time. Serum samples were analyzed for IgG concentration using a single radial immunodiffusion (SRID) test (98 samples) and total protein concentration using a temperature-compensating refractometer (98 samples). Colostrum and milk samples were analyzed for refractometry index (RI) using a Brix refractometer (71 samples). DVSTP concentration and DVRI were significantly correlated with serum IgG concentration. The negative predictive values (NPVs) of DVSTP concentration for detecting serum IgG concentrations<400 mg/dl and<800 mg/dl were 98.2% and 91.3% when the cutoff value is set to 0.4 mg/dl and 0.8 mg/dl, respectively. Furthermore, the NPVs of DVRI for detecting serum IgG concentrations<400 mg/dl and<800 mg/dl were 97.3% and 96.3% when the cutoff value is set to 6% and 10%, respectively. The results suggest that measurement of DVRI is useful in assessing FPT as an initial "stall-side" screening test, because it is easy, inexpensive to perform and allows for rapid interpretation.

[Evaluation of serological status of children following hepatitis B vaccination during infancy]. / Süt Çocuklugunda Hepatit B Asisi Uygulanan Çocuklarda Serolojik Durumun Degerlendirilmesi.

The aims of this study were to determine anti-HBs positivity in children who had received three doses of hepatitis B vaccine during infancy and to evaluate the factors that may affect the serological status. Local ethics committee approval was obtained at the beginning of the study. The study was carried out between December 2005 and October 2007 among children attending the outpatient clinics of medical school hospital. The study encompassed 912 children (393 female, 519 male; aged 1-5 years old) who had been immunized with three doses of intramuscular recombinant hepatitis B vaccine during infancy. All of the children were born to HBsAg negative mothers and did not have any known immune system problems. Sociodemographic characteristics and passive smoking status were gathered by a questionnaire. Anthropometric measurements were taken, and a detailed physical examination was carried out for each child. Blood samples were obtained to check serum HBsAg, anti-HBs and anti-HBc levels by commercial micro-ELISA (Sanofi Diagnostics Pasteur, Sydney) method. Levels of anti-HBs ≥ 10 mIU/ml were defined as seropositivity. In seronegative children, anti-HBs levels were re-checked 4 weeks after receiving one booster dose of hepatitis B vaccine. Of the children 877 (96.2%) were found anti-HBs positive, while all of them were negative for anti-HBc or HBsAg. Of children 34.8% were 12-23 months; 28.7% were 24-36 months; and 36.5% were 37-60 months-old, and anti-HBs negativity rate was higher in the older age group with a statistically significant difference (1.4%, 3.9% and 4.2%, respectively; p= 0.003). Anti-HBs antibodies were found negative in 2.8% of children who were born by vaginal route and in 5.8% of children who were born by cesarean section, the difference being statistically significant (p= 0.016). There were no significant differences between anti-HBs seropositivity and gender, working/ educational status of the mothers and the presence of smoking parents in the family (p> 0.05). Logistic regression analysis indicated that the factors that affect antibody levels in vaccinated children were the duration of breastfeeding only (4.77 ± 1.53 months in anti-HBs positives and 3.69 ± 2.13 months in negatives; p= 0.008), birth weight (3328.18 ± 318 g in anti-HBs positives and 3135.27 ± 488 g in negatives; p= 0.037) and pregnancy parity (anti-HBs was negative in 3.4% of children born from mothers who had < 2 parities, and 8.2% of children born from mothers who had < 3 parities; p= 0.037). The remaining 35 (3.8%) children with undetectable antibody levels became seropositive after one dose of hepatitis B vaccination, with the antibody levels of ≥ 100 mIU/ml. This response underlined the presence of immune memory in vaccinated children. The results of this study indicated that almost all 1-5 years old children who had received three doses of hepatitis B vaccine during infancy were protected from hepatitis B virus infection. It was concluded that similar studies should be carried out in different settings.

Epidemiology, control and management of an EBHS outbreak in captive hares.

Here we describe an outbreak of European brown hare syndrome (EBHS) in a captive hare population. The EBHS outbreak occurred in March 2009, at the beginning of the breeding season. Overall mortality was 53% out of an original population of 61 animals. Animals between five and eleven months showed a significantly higher mortality rate than other age classes. Pregnant females either aborted their foetuses and survived or died pregnant. All foetuses (n=10) of the pregnant hares were PCR positive for EBHSV. Only one offspring born during the outbreak survived. Shortly after the outbreak, the surviving hares developed a specific anti-EBHSV titre between 1:80 and 1:2560, which dropped to 1:10-1:160 nine months later. Hares between one and three years of age developed a significantly higher titre than hares younger than one year or older than four years. Offspring born after the outbreak showed a lower titre of 1:10, indicating passive antibody transfer via placenta and milk. After two months, the titre was not detectable any longer. In December 2009, the captive population was vaccinated against EBHS virus with inactivated virus prepared from the organs of infected hares. The titres after the first vaccination ranged from 1:10 to 1:640, and after the second vaccination from 1:10 to 1:320. To estimate the effect of EBHS on reproduction, we compared the breeding seasons 2008 and 2009. Several possible sources of infection of the colony are discussed, but the definite cause could not be determined.

Observational study to investigate vertically acquired passive immunity in babies of mothers vaccinated against H1N1v during pregnancy.

OBJECTIVE: The primary objective was to determine the proportion of babies who acquired passive immunity to A/H1N1v, born to mothers who accepted vaccination as part of the national vaccination programme while pregnant (during the second and/or third trimesters) against the novel A/H1N1v influenza virus (exposed group) compared with unvaccinated (unexposed) mothers. DESIGN: An observational study at three sites in the UK. The purpose was to determine if mothers immunised against A/H1N1v during the pandemic vaccination period transferred that immunity to their child in utero. SETTING: Three sites in the UK [Queen's Medical Centre, Nottingham; City Hospital, Nottingham (both forming University Hospitals Nottingham), and Leicester Royal Infirmary (part of University Hospitals Leicester)]. PARTICIPANTS: All pregnant women in the second and third trimester presenting at the NHS hospitals above to deliver were eligible to participate in the study. Women were included regardless of age, social class, ethnicity, gravida and parity status, past and current medical history (including current medications), ethnicity, mode of delivery and pregnancy outcome (live/stillbirth). INTERVENTIONS: At enrolment, participants provided written consent and completed a questionnaire. At parturition, venous cord blood was obtained for serological antibody analysis. Serological analysis was undertaken by the Respiratory Virus Unit (RVU), Health Protection Agency (HPA) Centre for Infections, London. MAIN OUTCOME MEASURES: The primary end point in the study was the serological results of the cord blood samples for immunity to A/H1N1v. Regarding a suitable threshold for the determination of a serological response consistent with clinical protection, this issue is somewhat complex for pandemic influenza. The European Medicines Agency (EMEA) Committee for Human Medicinal Products (CHMP) judges that a haemagglutination inhibition (HI) titre of 1 : 40 is an acceptable threshold. However, this level was set in the context of licensing plain trivalent seasonal vaccine, where a titre of 1 : 40 is but one of several related immunogenicity criteria, and supported by paired sera capable of demonstrating a fourfold rise in antibody titre in response to vaccination. The current study mainly investigated the effects of an AS03-adjuvanted monovalent vaccine, and it was not possible to obtain paired sera where the initial sample was taken before vaccination (in vaccinated subjects). Of possibly greater relevance is the fact that it has been established from the study of early outbreaks of pandemic influenza in secondary schools in the UK (HPA, unpublished observations) that an HI antibody titre of 1 : 32 seems to be the threshold for a humoral response to 'wild-type' A/H1N1v infection. On that basis, a threshold of 1 : 32 is at least as appropriate as one of 1 : 40, especially in unvaccinated individuals. Given the difficulties that would accrue by applying thresholds of 1 : 32 in unvaccinated patients and 1 : 40 in vaccinated patients, we have therefore applied a threshold of 1 : 32 and 1 : 40, to increase the robustness of our findings. Differences arising are described. A microneutralisation (MN) titre of 1 : 40 may be also used, although it is not part of the CHMP criteria for vaccine licensure. Nonetheless, we utilised this analysis as a secondary end point, based on a conservative threshold of 1 : 60. RESULTS: Reverse cumulative distribution percentage curves for haemagglutinin dilution and MN titres demonstrate background immunity in babies of unvaccinated mothers of 25%-30%. Humoral immunity in babies of vaccinated mothers was present in 80% of the group. The difference in positive immunity between the babies of unvaccinated and vaccinated mothers was statistically significant (chi-squared test, p < 0.001). CONCLUSIONS: Our findings reveal a highly significant difference in HI titres between babies born to mothers vaccinated with pandemic-specific vaccine against A/H1N1v during the 2009-10 pandemic period. The subjects recruited were comparable from a baseline perspective and thus do not represent different groups that otherwise could have introduced bias into the study. Continued circulation of 2009 A/H1N1-like viruses is uncertain, but is possible as seasonal influenza in years to come. It is possible that future seasonal waves may display increased virulence. Given the adverse outcomes experienced for a small proportion of pregnant women during the influenza pandemic of 2009-10, this study provides useful evidence to support vaccination in pregnancy to protect both the mother and baby. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Immune response in goats to two commercial foot-and-mouth disease vaccines and the assessment of maternal immunity in their kids.

In this investigation, the immune response of goats to two commercial foot-and-mouth disease vaccines (FMDV) was compared. Highest mean antibody titre was observed on days 60 and 21 in goats vaccinated with two doses of algel (group 1) and oil adjuvant (group 2) quadrivalent vaccines, respectively. There was no significant (P > 0.05) difference in mean antibody titre between the two vaccine groups. However, the antibody titres for type O fell below the protective titres by day 180 and 270 for groups 1 and 2, respectively. The mean maternal antibody titre was 0.610 +/- 0.0 immediately after birth. The highest mean maternal antibody titre was observed at 24 h after birth for all serotypes and then steadily declined. The maternal immunity of kids born to the vaccinated does was persistent up to 90 days after birth. There was no significant (P > 0.05) difference in mean maternal antibody titre between the two groups of goats for all four serotypes throughout the study period. The protective maternal antibody titre for serotype O was maintained only up to 1 week after birth, where for the other three serotypes A, C and Asia1 the protective maternal antibody titre was maintained up to 4 weeks of birth. Oil adjuvant vaccine may be used for control of FMDV in goats and the animals have to be revaccinated after 9 months, whereas the kids must be vaccinated at around 3-4 months after birth. Goats must be included in the FMDV control programmes and the same schedule for cattle can be followed.

Maternal antibodies reduce costs of an immune response during development.

Young vertebrates are dependent primarily on innate immunity and maternally derived antibodies for immune defense. This reliance on innate immunity and the associated inflammatory response often leads to reduced growth rates after antigenic challenge. However, if offspring have maternal antibodies that recognize an antigen, these antibodies should block stimulation of the inflammatory response and reduce growth suppression. To determine whether maternal and/or offspring antigen exposure affect antibody transmission and offspring growth, female Japanese quail (Coturnix japonica) and their newly hatched chicks were immunized. Mothers were immunized with lipopolysaccharide (LPS), killed avian reovirus vaccine (AR), or were given a control, phosphate-buffered saline, injection. Within each family, one-third of offspring were immunized with LPS, one-third were immunized with AR, and one-third were given the control treatment. Maternal immunization significantly affected the specific types of antibodies that were transmitted. In general, immunization depressed offspring growth. However, offspring immunized with the same antigen as their mother exhibited elevated growth in comparison to siblings immunized with a different antigen. This suggests that the growth suppressive effects of antigen exposure during development can be partially ameliorated by the presence of maternal antibodies, but in the absence of specific maternal antibodies, offspring are dependent on more costly innate immune defenses. Together, the results suggest that the local disease environment of mothers prior to reproduction significantly affects maternal antibody transmission and these maternal antibodies may allow offspring to partially maintain growth during infection in addition to providing passive humoral immune defense.

Use of Fourier-transform infrared spectroscopy for the diagnosis of failure of transfer of passive immunity and measurement of immunoglobulin concentrations in horses.

BACKGROUND: The economic, accurate, and rapid screening of foals for failure of transfer of passive immunity (FPT) is essential to ensure timely intervention. HYPOTHESIS: Infrared (IR) spectroscopy of foal sera and pattern recognition may be used to diagnose FPT and quantify serum IgG. SAMPLES: Sera from 194 foals (24-72 hours) with serum immunoglobulin G (IgG) concentrations determined previously by radial immunodiffusion assay (RID) were used. METHODS: IR spectra were recorded for the serum samples, and the data were randomly divided into training and independent test sets, each containing both FPT-positive (IgG <400 mg/dL) and non-FPT samples. A genetic optimal region selection algorithm and linear discriminant analysis were used to partition the training spectra, and the resulting classifier was then validated by comparing the IR-predicted FPT status for each of the test samples to that provided by the RID IgG assay. A quantitative IR-based assay for IgG was developed using partial least squares (PLS) and validated by testing its ability to predict IgG concentrations. RESULTS: Specificity, sensitivity, and accuracy for the combined data were 92.5, 96.8, and 95.9%, respectively. Corresponding positive (88.1%) and negative predictive (98.0%) values determined a success rate of 95-97% as compared to RID-based IgG concentrations. The IR-based quantitative assay yielded correlation coefficients for IR spectroscopy versus RID-based IgG concentrations of 0.90 and 0.86 for the training and test sets, respectively. CONCLUSIONS AND CLINICAL IMPORTANCE: The overall performance of the IR-based test was similar to that of the colorimetric assay and was superior and more economic than other available tests.

Rotavirus immunoglobulin levels among Indian mothers of two socio-economic groups and occurrence of rotavirus infections among their infants up to six months.

Rotavirus specific immunoglobulin levels were estimated and compared between mothers undergoing delivery from two socio-economic groups (n = 56 each) by direct/capture ELISA. IgG geometric mean titers (GMTs) of cord blood/mothers serum at delivery were significantly higher in the higher socio-economic group (HSG) as compared to the lower socio-economic group (LSG) (P < 0.01). Thirty-four mother-infant pairs (17 from each group) were followed-up up to 6 months for the occurrence of rotavirus infections. All follow-up LSG infants were low birth weight as against none from the HSG. Detection of virus by ELISA/RT-PCR and considering IgM/IgA seroconversion as an index of infection, 11 and 17 infants from HSG and LSG respectively had rotavirus infections. Two infants from LSG were hospitalized for severe rotavirus diarrhea but none from the HSG. Lower IgG levels in the LSG mother-infant pairs as compared to those of HSG, suggests a possible role of under nutrition in development of antibodies and immunity. Infants from the HSG who did not have rotavirus infections had significantly higher IgG GMTs in cord blood and serum samples at 6 months, than those HSG infants who had symptomatic/asymptomatic rotavirus infections (P < 0.05). In conclusion, fewer rotavirus infections occur when cord blood contains higher level of IgG antibodies, suggesting a role of protective immunity.