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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. 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. 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. 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.).

Postnatal colonization of the body with microbes is assumed to be the main stimulus to postnatal immune development. By transiently colonizing pregnant female mice, we show that the maternal microbiota shapes the immune system of the offspring. Gestational colonization increases intestinal group 3 innate lymphoid cells and F4/80⁺CD11c⁺ mononuclear cells in the pups. Maternal colonization reprograms intestinal transcriptional profiles of the offspring, including increased expression of genes encoding epithelial antibacterial peptides and metabolism of microbial molecules. Some of these effects are dependent on maternal antibodies that potentially retain microbial molecules and transmit them to the offspring during pregnancy and in milk. Pups born to mothers transiently colonized in pregnancy are better able to avoid inflammatory responses to microbial molecules and penetration of intestinal microbes.

Abstract Maternal immune responses can promote allergy development in offspring, as shown in a model of increased susceptibility to asthma in babies of ovalbumin (OVA)-sensitized and -challenged mother mice. We investigated whether inflammatory responses to air pollution particles (diesel exhaust particles, DEP) or control “inert” titanium dioxide (TiO2) particles are enhanced during pregnancy and whether exposure to particles can cause increased neonatal susceptibility to asthma. Pregnant BALB/c mice (or nonpregnant controls) received particle suspensions intranasally at Day 14 of pregnancy. Lung inflammatory responses were evaluated 48 hours after exposure. Offspring of particle- or buffer-treated mothers were sensitized and aerosolized with OVA, followed by assays of airway hyperresponsiveness (AHR) and allergic inflammation (AI). Nonpregnant females had the expected minimal response to “inert” TiO2. In contrast, pregnant mice showed robust and persistent acute inflammation after both TiO2 and DEP. Genomic profiling identified genes differentially expressed in pregnant lungs exposed to TiO2. Neonates of mothers exposed to TiO2 (and DEP, but not PBS) developed AHR and AI, indicating that pregnancy exposure to both “inert” TiO2 and DEP caused increased asthma susceptibility in offspring. We conclude that (1) pregnancy enhances lung inflammatory responses to otherwise relatively innocuous inert particles; and (2) exposures of nonallergic pregnant females to inert or toxic environmental air particles can cause increased allergic susceptibility in offspring.

Neurological disorders are among the main clinical problems affecting preterm children and often result in the development of communication and learning disabilities later in life. Several factors are of importance for brain development, however the role of immunoglobulins (passive immunity transfer) has not yet been investigated. Piglets are born agammaglobulinemic, as a result of the lack of transfer of maternal immunoglobulins in utero, thus, they serve as an ideal model to mimic the condition of immunoglobulin deficiency in preterm infants. Thirty six, unsuckled newborn piglets were fed an infant formula or colostrum and supplemented orally or intravenously with either species-specific or foreign immunoglobulin and then compared to both newborn and sow-reared piglets. Two days after the piglets were born behavioural tests (novel recognition and olfactory discrimination of conspecifics scent) were performed, after which the piglets were sacrificed and blood, cerebrospinal fluid and hippocampi samples were collected for analyses. Both parameters of neuronal plasticity (neuronal maturation and synapse-associated proteins) and behavioural test parameters appeared to be improved by the appearance of species-specific porcine immunoglulin in the circulation and cerebrospinal fluid of the piglets. In conclusion, we postulate possible positive clinical effects following intravenous infusion of human immunoglobulin in terms of neuronal plasticity and cognitive function in preterm infants born with low blood immunoglobulin levels.

•Maternal Abs may inhibit the infant’s humoral immune response to several antigens.•Infant CMI responses in presence of maternal Abs are less extensively studied.•Maternal Abs allow priming of CMI responses after infant vaccination.•Exact mechanisms and influences of maternal Abs on T cells remain unknown. During the last few decades, maternal immunization as a strategy to protect young infants from infectious diseases has been increasingly recommended, yet some issues have emerged. Studies have shown that for several vaccines, such as live attenuated, toxoid and conjugated vaccines, high maternal antibody titers inhibit the infant’s humoral immune response after infant vaccination. However, it is not clear whether this decreased antibody titer has any clinical impact on the infant’s protection, as the cellular immune responses are often equally important in providing disease protection and may therefore compensate for diminished antibody levels. Reports describing the effect of maternal antibodies on the cellular immune response after infant vaccination are scarce, probably because such studies are expensive, labor intensive and utilize poorly standardized laboratory techniques. Therefore, this review aims to shed light on what is currently known about the cellular immune responses after infant vaccination in the presence of high (maternal) antibody titers both in animal and human studies. Overall, the findings suggest that maternally derived antibodies do not interfere with the cellular immune responses after infant vaccination. However, more research in humans is clearly needed, as most data originate from animal studies.

BackgroundThe World Health Organization (WHO) recommends the discontinuation of oral poliovirus vaccine after eradication of wild poliovirus. Studies assessing inactivated poliovirus vaccine (IPV) immunogenicity in tropical countries, using the WHO Expanded Programme on Immunization (EPI) schedule, have been limited MethodsWe conducted a randomized clinical trial in Ponce, Puerto Rico. Infants were assigned to 1 of 2 study arms: those in the EPI arm received IPV at 6, 10, and 14 weeks of age, and those in the US arm received IPV at 2, 4, and 6 months of age. Neutralizing antibody titers against poliovirus types 1, 2, and 3 were tested on serum specimens obtained before administration of the first dose of IPV and 28–45 days after administration of the last dose of IPV ResultsSeroconversion rates for the EPI (n=225) and US (n=230) arms, respectively, were 85.8% and 99.6% for poliovirus type 1 (P<.001), 86.2% and 100% for poliovirus type 2 (P<.001), and 96.9% and 99.1% for poliovirus type 3 (P=.08). Seroconversion rates were lower among infants in the EPI arm who had high maternal antibody levels for all 3 poliovirus types (P<.001) ConclusionsThe EPI schedule resulted in lower seroconversion rates for poliovirus types 1 and 2. These results are relevant for tropical countries planning to use IPV in a posteradication environment

Enterotoxaemia is a disease with a high associated mortality rate, affecting beef and veal calves worldwide, caused by C. perfringens alpha toxin and perfringolysin. A longitudinal study was conducted to determine the dynamics of antibodies against these toxins in 528 calves on 4 beef and 15 veal farms. The second study aimed to determine the effect of solid feed intake on the production of antibodies against alpha toxin and perfringolysin. The control group only received milk replacer, whereas in the test group solid feed was provided. Maternal antibodies for alpha toxin were present in 45% of the veal calves and 66% of the beef calves. In beef calves a fluent transition from maternal to active immunity was observed for alpha toxin, whereas almost no veal calves developed active immunity. Perfringolysin antibodies significantly declined both in veal and beef calves. In the second study all calves were seropositive for alpha toxin throughout the experiment and solid feed intake did not alter the dynamics of alpha and perfringolysin antibodies. In conclusion, the present study showed that veal calves on a traditional milk replacer diet had significantly lower alpha toxin antibodies compared to beef calves in the risk period for enterotoxaemia, whereas no differences were noticed for perfringolysin.

In 2013, pertussis immunization (Tdap) for pregnant women was implemented in Colombia to protect newborns in response to increased pertussis incidence. To assess the effect of Tdap maternal immunization on the concentration of mother/umbilical cord antibodies and the occurrence of pertussis in infants during their first six months of life. A cohort study in eight randomly selected hospitals in Medellin and metropolitan area of Antioquia, Colombia was conducted in 2015–2016. IgG PT antibody levels in paired maternal and umbilical cord sera were measured from 805 mothers immunized recruited during labor and 200 mothers recruited during the prenatal care before immunization and followed until delivery. Antibodies were analyzed by commercial ELISA kits. 896 infants were followed to detect acute respiratory infections and paroxysms of coughing, inspiratory whoop, apnea, cyanosis or post-tussive vomiting. For laboratory confirmation, B. pertussis- specific real time PCR was performed. We observed a high prevalence of titers >100 IU/mL (mother: 18.40% [95% CI 16–21%]; umbilical cord: 23.1% [95% CI 19.2–27.4%]), positive correlation of umbilical cord and maternal antibodies, higher antibody concentration in vaccinated than in non-vaccinated mothers and significant difference in antibody levels before and after vaccination (Wilcoxon test p = 0.000). The trans placental transport ratio was higher if the mother was vaccinated between 26 and 30 weeks of pregnancy and maximum eight weeks before delivery. Two cases of pertussis were confirmed in infants (incidence of 1.99 per 1000). The expected effect of Tdap maternal vaccination against pertussis was observed.

Maternal antibodies are transferred from hens to the chicks via the egg. To gain insight into maternal antibody transfer and endogenous production of antibodies in broiler chicks, total IgY, IgA, IgM, as well as anti-Newcastle disease virus (NDV) and anti-infectious bronchitis (IBV) antibody levels were examined in the dams' plasma, egg yolks, egg whites, and chicks' plasma on d 3, 7, 14, and 21. Blood was collected from 39-wk-old breeder hens (line 1, n = 17; line 2, n = 21). Fertile eggs were used for antibody extraction from the egg yolks and egg whites (4 to 5 eggs/dam) and for hatching. Unvaccinated chicks (4 to 5 chicks/dam) were reared in a HEPA-filtered room and were bled on d 3, 7, 14 and 21. Based on ELISA methods, plasma levels of IgY and IgM were higher (P < 0.0001), and those of IgA were similar (P = 0.31), in line 2 compared with line 1. Egg yolk IgY and IgA, as well as egg white IgY, IgA, and IgM levels were higher in line 2 compared with line 1 (P < 0.0001). Independent of line of chicken, the percentage dam-to-chick (3 d) plasma transfer of IgY was estimated to be approximately 30%, with that for IgM and IgA less than 1%. Chicks synthesized IgM first, followed by IgA and IgY. Anti-NDV and anti-IBV antibodies were detected in the dams' plasma, egg yolks, and in the chicks' plasma on d 3 and 7, with line 2 having higher anti-IBV and lower anti-NDV levels than line 1 in all samples (P < 0.0001). In summary, IgY levels, total or antigen-specific, in the dams' plasma or eggs were found to be a direct indicator of maternal antibody transfer to the chicks' circulation, with an expected percentage transfer of approximately 30%. This knowledge, together with the observed time course of endogenous antibody production in broiler chicks, may find direct application in formulating strategies for protecting chicks, especially during the first few weeks of age when their immune system is not yet fully functional.

The objective of this study was to investigate the effect of method of feeding (nipple bottle vs. esophageal tube feeder) on passive transfer of immunoglobulin (Ig) G when either a large or small volume of colostrum was fed. Newborn bull calves were removed from the dam before suckling and randomly assigned to 1 of 4 colostrum replacer (CR) treatment groups: 1.5L (100g of IgG) of CR fed using a nipple bottle (group 1; n=24); 1.5L (100g of IgG) of CR fed using an esophageal tube feeder (group 2; n=24); 3.0L (200g of IgG) of CR fed using a nipple bottle (group 3; n=24), or 3.0L (200g of IgG) of CR fed using an esophageal tube feeder (group 4; n=25). Blood samples collected at 24h of age showed that serum IgG levels were significantly greater in calves fed large (3L) volumes of CR compared with calves fed small (1.5L) volumes of CR, regardless of feeding method. These differences were attributed to the larger mass of IgG ingested by calves fed 3L of CR (200g of IgG) compared with calves fed 1.5L of CR (100g of IgG). For calves fed small (1.5L) volumes of colostrum, serum total protein (TP, g/dL), serum IgG (IgG, mg/mL), acceptable passive transfer rates (APT, %), and apparent efficiency of absorption of IgG (AEA, %) were significantly greater for calves fed with a bottle (TP=5.3g/dL; IgG=12.5mg/mL; APT=100%; AEA=51.1%) compared with calves fed with an esophageal tube feeder (TP=5.0g/dL; IgG=9.8mg/mL; APT = 41.7%; AEA = 40.5%). However, for calves fed large (3L) volumes of colostrum, there was no difference in passive transfer indices for calves fed with a bottle (TP=5.8g/dL; IgG=19.7mg/mL; APT = 100%; AEA=41.1%) compared with calves fed with an esophageal tube feeder (TP=5.9g/dL; IgG=18.7mg/mL; APT=100%; AEA=39.0%).