Passive Transfer Of Maternal Immunity Research Articles

A Virus-like Particle-Based F4 Enterotoxigenic Escherichia coli Vaccine Is Inhibited by Maternally Derived Antibodies in Piglets but Generates Robust Responses in Sows.

F4-positive enterotoxigenic Escherichia coli is associated with diarrhea and poor growth outcomes in neonatal and newly weaned piglets and is thus a major economic and welfare burden in the swine industry. Vaccination of sows with F4 fimbriae protects against the neonatal disease via passive transfer of maternal immunity. However, this strategy does not protect against infection post-weaning. Consequently, prevention and treatment methods in weaner pigs heavily rely on the use of antimicrobials. Therefore, in order to reduce antimicrobial consumption, more effective prophylactic alternatives are needed. In this study, we describe the development of a capsid virus-like particle (cVLP)-based vaccine targeting the major F4 fimbriae subunit and adhesion molecule, FaeG, and evaluate its immunogenicity in mice, piglets, and sows. cVLP-display significantly increased systemic and mucosal antibody responses towards the recombinant FaeG antigen in mice models. However, in piglets, the presence of anti-F4 maternally derived antibodies severely inhibited the induction of active humoral responses towards the FaeG antigen. This inhibition could not be overcome, even with the enhanced immunogenicity achieved via cVLP display. However, in sows, intramuscular vaccination with the FaeG.cVLP vaccine was able to generate robust IgG and IgA responses that were comparable with a commercial fimbriae-based vaccine, and which were effectively transferred to piglets via colostrum intake. These results demonstrate that cVLP display has the potential to improve the systemic humoral responses elicited against low-immunogenic antigens in pigs; however, this effect is dependent on the use of antigens, which are not the targets of pre-existing maternal immunity.

Investigation of total immunoglobulin G concentration, heavy chain antibody levels, and neutrophil to lymphocyte ratio in female camels and their newborn calves.

Camels belong to a group of animals, where the structure of placenta does not allow intrauterine transfer of maternal immunoglobulins to the fetus and maternal immunity is exclusively transferred by colostrum to the newborn calf. There are few studies on the passive transfer of maternal immunity in the dromedary camel. This study determined total immunoglobulin G concentration, heavy chain antibody (HCAbs) levels, and neutrophils to lymphocytes ratio (NLR) in female camels and their newborn calves. For this, samples were collected from nine she-camels (blood and colostrum) and their calves (blood). IgG concentration and HCAb level were determined in mother serum and colostrum as well as in calf serum using ELISA. The NLR was calculated after the estimation of relative fractions of neutrophils and lymphocytes in collected blood samples using a blood cell analyzer. Both IgG and HCAbs were higher concentrated in camel colostrum than in mother serum. At parturition and before the first colostrum intake, calf serum did not contain any measurable concentration of IgG and only low levels of HCAbs. After colostrum consumption, a rise in IgG and HCAb levels was observed in calf serum. For total IgG, a minimum was reached on day 30 postnatum. While a significant increase in IgG concentration was seen on day 60 postnatum, no significant rise was measured in HCAbs at that age. Only post-colostrum IgG levels in calf serum correlated positively with IgG levels in mother colostrum. Directly after birth, newborn calves showed significantly higher NLR than their mothers. This indicates a pro-inflammatory nature of the calf immune response. The decrease of the NLR on day 60 postnatum may argue for the maturation of the calf immune response at this age.

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

In newborn foals the absorption of colostrum immunoglobulins in the small intestine is maximal up to 8hours after birth and then progressively decreases to become null after 24hours 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. 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. Assay validation using samples collected for clinical purposes. 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. 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 8g/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. Variable times of sample extraction after colostrum suckling, over the study period. 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.

Maternal Antiviral Immunoglobulin Accumulates in Neural Tissue of Neonates To Prevent HSV Neurological Disease.

ABSTRACTWhile antibody responses to neurovirulent pathogens are critical for clearance, the extent to which antibodies access the nervous system to ameliorate infection is poorly understood. In this study on herpes simplex virus 1 (HSV-1), we demonstrate that HSV-specific antibodies are present during HSV-1 latency in the nervous systems of both mice and humans. We show that antibody-secreting cells entered the trigeminal ganglion (TG), a key site of HSV infection, and persisted long after the establishment of latent infection. We also demonstrate the ability of passively administered IgG to enter the TG independently of infection, showing that the naive TG is accessible to antibodies. The translational implication of this finding is that human fetal neural tissue could contain HSV-specific maternally derived antibodies. Exploring this possibility, we observed HSV-specific IgG in HSV DNA-negative human fetal TG, suggesting passive transfer of maternal immunity into the prenatal nervous system. To further investigate the role of maternal antibodies in the neonatal nervous system, we established a murine model to demonstrate that maternal IgG can access and persist in neonatal TG. This maternal antibody not only prevented disseminated infection but also completely protected the neonate from neurological disease and death following HSV challenge. Maternal antibodies therefore have a potent protective role in the neonatal nervous system against HSV infection. These findings strongly support the concept that prevention of prenatal and neonatal neurotropic infections can be achieved through maternal immunization.

Optimisation of the zinc sulphate turbidity test for the determination of immune status

Failure of passive transfer of maternal immunity occurs in calves that fail to absorb sufficient immunoglobulins from ingested colostrum. The zinc sulphate turbidity test has been developed to test bovine...

Comparison of rapid laboratory tests for failure of passive transfer in the bovine

BackgroundFailure of passive transfer of maternal immunity via colostrum can occur in the bovine, and a number of blood tests have been developed to test calves for this failure. It is not clear which test is most suitable for this purpose. The objective was to examine the most commonly used tests for failure of passive transfer and to decide which is most suitable for routine laboratory use. 126 serum samples were taken from calves of dairy cows after birth but prior to colostrum feeding, and at 48 h of age. Five different tests were compared against radial immunodiffusion which is considered the appropriate reference method. These tests were serum gamma-glutamyltransferase levels, serum protein levels, serum globulin levels, an enzyme linked immunosorbent assay and the zinc sulphate turbidity test.ResultsThe tests examined displayed high sensitivity but widely varying specificity. Examination of the use of different cut-off points allowed some improvement in specificity at the expense of sensitivity, but the tests which had performed best at the original cut-off points still displayed the best performance. Gamma-glutamyltransferase levels as a measure of colostrum absorption returned, in this study, the best balance between sensitivity and specificity. The ELISA used in this study and serum globulin levels displayed performance similar to the gamma-glutamyltransferase levels. Serum total protein was less successful than others examined at providing both sensitivity and specificity but may, when performed via refractometer, be useful for on-farm testing. As currently performed the poor sensitivity for which the zinc sulphate turbidity test is most often criticized is evident. Modification of the cut-off point to increase specificity is less successful at balancing these parameters than the ELISA, gamma-glutamyltransferase levels, and globulin levels.ConclusionsGamma-glutamyltransferase levels, ELISA testing and circulating globulin levels performed best in detecting failure of passive transfer in serum samples, although all three had some practical considerations.

Passive transfer of maternal immunity in the dromedary (Camelus dromedarius), involvement of heavy chain antibodies.

In many mammalian species, newborns are agammaglobulinemic; thus, colostrum and milk are the main sources of early protective antibodies. These antibodies are produced in the mother's serum and transferred to mammalian glands a few days before parturition. Here, we have studied the transfer of immunity from a she-camel immunized with human serum albumin (HSA) to her calf via colostrum and milk. Our results show that HSA-specific antibodies are produced in the mother's serum and are subsequently transferred to her colostrum. These specific antibodies are then transferred by suckling to the calf. The calf serum did not contain HSA-reactive antibodies at parturition and before the first feed, after suckling, a rise in reactivity was observed peaking at 24 h postpartum. The involvement of heavy chain antibodies (HCAbs) in the process of immunity transfer was also examined, and it was found that they were also transferred from the colostrum to the calf serum like conventional antibodies.

Prenatal passive transfer of maternal immunity in Asian elephants (Elephas maximus)

Asian (Elephas maximus) and African (Loxodonta africana) elephants exhibit characteristics of endotheliochorial placentation, which is common in carnivore species and is associated with modest maternal to fetal transplacental antibody transfer. However, it remains unknown whether the bulk of passive immune transfer in elephants is achieved prenatally or postnatally through ingestion of colostrum, as has been documented for horses, a species whose medical knowledgebase is often extrapolated for elephants. To address this issue, we took advantage of the fact that many zoo elephants are immunized with tetanus toxoid and/or rabies vaccines as part of their routine health care, allowing a comparison of serum antibody levels against these antigens between dams and neonates. Serum samples were collected from 3 newborn Asian elephant calves at birth (before ingestion of colostrum); 2–4 days after birth; and 2–3 months of age. The findings indicate that the newborns had anti-tetanus toxoid and anti-rabies titers that were equivalent to or higher than the titers of their dams from birth to approximately 3 months of age, suggesting that the majority of maternal-to-fetal transfer is transplacental and higher than expected based on the architecture of the Asian elephant placenta.

Passive Immunity in Ontario Dairy Calves and Investigation of Its Association with Calf Management Practices

Adequate passive transfer of maternal immunoglobulin is important for optimal health and performance in newborn dairy calves. From June to October 2003 and January to April 2004, blood samples were collected from 961 dairy calves 0 to 8 d of age on 11 farms in southwestern Ontario. This was followed by a second study conducted from May to October 2004, in which similar samples were taken from 422 calves up to 8 d of age on 119 dairy farms throughout southern Ontario. For each sample collected, serum refractometry was used to evaluate serum total protein (TP) as a measure of passive transfer of maternal immunity. During each study, producers were asked to provide information on calf management practices, including details of colostrum feeding. Data were analyzed to assess the levels of maternal immunity present in the calves, and to investigate whether these were associated with any calf management or colostrum feeding practices used on the farms. Serum TP readings ranged from 3.5 to 9.8g/dL. Controlling for any effects of variation between farms, we found no statistically significant difference in serum TP levels, or risk of failure of passive transfer (FPT), between heifer and bull calves. The odds of FPT in calves on farms where more than 75% of cows were usually allowed to remain with their calves for more than 3h after calving were significantly higher than the odds of FPT in calves on farms where dams and calves were separated within 3h of the birth. Furthermore, an increased volume of colostrum given to calves within 6h of birth was significantly associated with a reduced risk of FPT in calves. Information from this work provides valuable insight into the efficiency of passive transfer in newborn dairy calves in southern Ontario.

Evaluation of inflammation and immunity in cats with spontaneous parvovirus infection: Consequences of recombinant feline interferon-ω administration

Administration of recombinant feline interferon-ω (rFeIFN) has been proposed for the prophylaxis of canine and feline parvovirosis. In the present study, the influence of the administration of rFeIFN on blood markers of inflammation (α-globulins, α 1-acid glycoprotein) and immune system activation (γ-globulins, IgG, IgM, specific anti-feline parvovirus IgG or IgM) was evaluated in a cattery developing an outbreak of feline panleukopenia due to feline parvovirus (FPV) infection few days after initial administration of rFeIFN. Kittens ( n = 23) were injected with rFeIFN (1 MU/kg subcutaneoulsy, once a day for 3 days) and their blood parameters were compared with those of 17 untreated cats. Cats that survived the outbreak were vaccinated and re-sampled 1 month after the last rFeIFN administration. Time of emergence of clinical signs and survival rate were not significantly different between the two groups. Controls and treated cats surviving the infection had high levels of γ-globulins, total- and anti-FPV specific IgGs, likely due to passive transfer of maternal immunity. Compared to controls, treated kittens had lower levels of α 1-globulins and higher mean values of γ-globulins and immunoglobulins. Data from samples collected after vaccination revealed a higher level of γ-globulins, total- and anti-FPV specific IgGs in treated kittens, compared with controls, suggesting that rFeIFN stimulates antibody production. Based on this results, rFeIFN should be administered to the queen, to increase passive maternal immunity, or to kittens before introduction in a potentially contaminated environment.

Effect of plasma transfusion on neutrophil function in healthy and septic foals

To evaluate the effect of plasma transfusion on phagocytosis and oxidative burst activity of peripheral blood neutrophils from healthy and septic equine neonates with sub-optimal passive transfer of maternal immunity. Nine healthy and seven septic foals with suboptimal passive transfer of maternal immunity (serum IgG < 8 g/L) presented to participating veterinary hospitals for plasma transfusion, and seven healthy foals less than 7 days of age and with circulating IgG concentrations > or = 8 g/L. Foals with serum IgG concentrations < 8 g/L were assessed as healthy or septic. Sepsis was recognised by positive bacterial cultures and/or sepsis scores of > or = 11. All foals received between 1 and 3 L of plasma to boost circulating IgG concentrations to > or = 8 g/L. Serum IgG concentrations were determined before and following transfusion by glutaraldehyde coagulation test and confirmed by single radial immunodiffusion assays. Neutrophil phagocytosis and oxidative burst activity were determined before plasma transfusion and at 0 h, 12 h, 24 h, 48 h and 5 d following treatment. Neutrophil function from seven healthy foals less than 7 d of age and with circulating IgG concentrations of > or = 8 g/L was similarly evaluated on a single occasion. Plasma treatment significantly increased circulating IgG concentrations for healthy and septic foals. Oxidative burst activity of neutrophils from septic foals was significantly increased 5 days following treatment, relative to 0 h post treatment. Other differences were not significant but suggested a transient decrease in phagocytosis by neutrophils from healthy foals and increased phagocytosis by neutrophils from septic foals immediately following transfusion. Oxidative burst activity of neutrophils from septic foals tended to be less than that of healthy foals at all sampling times. Serum IgG concentrations were not correlated with neutrophil phagocytosis, but were correlated with oxidative burst activity. Plasma transfusion did not improve neutrophil function of healthy foals, suggesting that such treatment may be of equivocal benefit for healthy neonates. Conversely, improved neutrophil function was observed following treatment of septic foals, suggesting that plasma transfusion was beneficial for these foals. Oxidative burst activity of neutrophils from septic foals was lower than that of neutrophils from healthy foals and was significantly improved 5 days post treatment, when compared with values obtained immediately following treatment.

Compartments within the lymph node cortex of calves and adult cattle differ in the distribution of leukocyte populations: An immunohistochemical study using computer-assisted morphometric analysis

The combination of an immunohistochemical technique and a panel of monoclonal antibodies was used to investigate the presence of leukocyte populations in the distal jejunal lymph node of 3–4 week old calves and adult cattle. The application of computer-assisted morphometric analysis enabled information to be obtained on the distribution of leukocyte populations in lymphoid compartments of the lymph node cortex. Semi-quantitative estimates of the areas of staining in histological sections showed that calves possessed significantly fewer B-cells and CD4+ cells in the outer cortex and significantly fewer T-cells (CD4+, CD8+ and γδ T-cells) in the deep cortex. These findings were interpreted to be a possible consequence of immunosuppression resulting from the passive transfer of maternal immunity in colostrum. The presence of some B-cell follicles in the region defined as the deep cortex suggested the on-going differentiation of this predominantly T-cell compartment. The larger presence of interdigitating cells (IDC) in the deep cortex of calves than adults was suggested by significantly larger CD1+ populations and it was argued that this could be the result of the confrontation with exogenous antigen faced by calves in early postnatal life. Antigen presenting populations, pan MHC II + and MHC II DQ + populations, were increased in all compartments of calf lymph nodes but were not significantly different from the populations in adult lymph nodes. Variance component analysis of the data generated in the present study showed that the image analysis technique was an effective and statistically powerful approach to investigate leukocyte populations within the specific microenvironments of the lymph node.

Field methods for estimating serum immunoglobulin concentrations in newborn kids

Serum samples were collected from 41 newborn kids between 48–96 h of age after consumption of colostrum at birth. Serum immunoglobulin (Ig) concentrations were determined using a quantitative, spectrophotometric zinc sulfate turbidity assay, and total serum protein was determined using a refractometer. A qualitative sodium sulfite precipitation test was also performed to evaluate Ig content using 14%, 16% and 18% sodium sulfite solutions. Failure of passive transfer of maternal immunity (FPT) in newborn kids was defined as a serum Ig content of less than 1200 mg/dl, and 1200 mg/dl or above as successful passive transfer (SPT). Based on these criteria, and using a total serum protein level of 5.4 g/dl as the cutoff point, refractometry correctly identified 17 of 17 kids (100%) with FPT and 20 of 24 kids (83.3%) with SPT. Four kids (6.7%) with adequate serum Ig levels were misidentified as FPT. Sodium sulfite precipitation at 14% correctly identified 17 of 17 kids (100%) with FPT, but only 3 of 24 (12.5%) with SPT. Twenty-one of 24 kids (87.5%) with adequate serum Ig levels were misidentified as FPT. Sodium sulfite at 16% correctly identified all 17 kids with FPT and 19 of 24 kids (79.2%) with SPT. Five of 24 kids (20.8%) were misidentified as FPT. Sodium sulfite at 18% correctly identified all 17 kids with FPT and 22 of 24 kids (91.7%) with SPT. Only two of 24 kids (8.3%) were misidentified as FPT. It was concluded that the sodium sulfite precipitation test, with an 18% solution, was a useful method for screening young goat kids for FPT or confirming SPT in the field. Total protein determination of refractometry using a cutoff value of 5.4 g/dl was also an acceptable screening method but less reliable than the sodium sulfite precipitation test. When using either method as a screening test, it is recommended that serum from individuals with a provisional diagnosis of FPT be submitted to a laboratory for a quantitative determination of Ig concentration to avoid cases of misidentification.

Failure of passive transfer of colostral immunity in the foal: incidence, and the effect of stud management and plasma transfusions

The importance of colostrum for the passive transfer of maternal immunity to foals is well recognised. This survey reports the incidence of the failure of passive transfer of colostral immunity in thoroughbred foals in the United Kingdom during 1988 to 1990, and the effect of plasma transfusions on IgG levels in a group of them. The incidence of disease in these foals first month of life is also recorded.