Neonatal Immunity Research Articles

Neonatal immune cells have heightened responses following in-utero exposure to chorioamnionitis or COVID-19.

Chorioamnionitis alters neonatal immune responses. Gestational COVID-19 infection is associated with adverse pregnancy outcomes, but its impact on neonatal immunity is unclear. We hypothesized that gestational COVID-19 exposure would result in exaggerated neonatal immune responses, similar to chorioamnionitis-exposed neonates. Term umbilical cord blood mononuclear cells (CBMCs) were isolated from neonates exposed to chorioamnionitis, gestational COVID-19 or unexposed controls. CBMCs were cultured and stimulated with heat-killed Escherichia coli, Streptococcus agalactiae or Staphylococcus epidermidis. A multiplexed protein assay was used to measure cytokine levels in cell culture supernatants and flow cytometry was used to evaluate cellular-level cytokine expression. Both chorioamnionitis-exposed and COVID-19 exposed CBMCs demonstrated upregulation of IL-1β and IL-6 compared to unexposed CBMCs, while only COVID-19 exposure resulted in IL-8 upregulation. There were no differences between chorioamnionitis-exposed and COVID-19 exposed CBMCs when these groups were directly compared. Flow cytometry demonstrated immune cell subset specific differences in cytokine expression between the exposure groups. The fetal/neonatal response to maternal inflammation differed based on immune cell subset and etiology of inflammation, but the global neonatal cytokine responses were similar between exposure groups. This suggests that targeting perinatal inflammation rather than the specific etiology may be a possible therapeutic approach. Neonatal immune cells have similar pathogen-associated global cytokine responses, but different cell-level immune responses, following in-utero exposure to chorioamnionitis or COVID-19. This is the first study to directly compare immune responses between neonates exposed to chorioamnionitis and COVID-19. This suggests that the fetal/neonatal cellular response to perinatal inflammation differs based on the etiology and severity of maternal inflammation, but still results in a similar overall inflammatory profile regardless of the cause of perinatal inflammation.

IL6 suppresses vaccine responses in neonates by enhancing IL2 activity on T follicular helper cells

The inability of neonates to develop CD4+FoxP3-CXCR5hiPD-1hi T follicular helper (TFH) cells contributes to their weak vaccine responses. In previous studies, we measured diminished IgG responses when IL-6 was co-injected with a pneumococcal conjugate vaccine (PCV) in neonatal mice. This is in sharp contrast to adults, where IL-6 improves vaccine responses by downregulating the expression of IL-2Rβ on TFH cells and protecting them from the inhibitory effect of IL-2. In this study, we found that splenic IL-6 levels rapidly increased in both adult and neonatal mice following immunization, but the increase in neonatal mice was significantly more than that of adult mice. Moreover, immunized neonatal TFH cells expressed significantly more IL-2 as well as its receptors, IL-2Rα and IL-2Rβ, than the adult cells. Remarkably, IL-6 co-injection with PCV vaccine further increased the production of IL-2 and the expression of its receptors by neonatal TFH cells, whereas excess IL-6 had totally opposite effect in immunized adult mice. Underscoring the role of IL-6 in activating the IL-2 mediated suppression of vaccine responses, immunization of IL-6 knock-out neonates led to improved antibody responses accompanied by expanded TFH cells as well as lower levels of IL-2 and IL-2 receptors on TFH cells. Moreover, CpG containing PCV improved TFH response in neonates by suppressing the expression of IL-2 receptors on TFH cells and inhibiting IL-2 activity. These findings unveil age-specific differences in IL-6 mediated vaccine responses and highlight the need to consider age-related immunobiological attributes in designing vaccines.

Quantitative mechanistic model reveals key determinants of placental IgG transfer and informs prenatal immunization strategies.

Transplacental antibody transfer is crucially important in shaping neonatal immunity. Recently, prenatal maternal immunization has been employed to boost pathogen-specific immunoglobulin G (IgG) transfer to the fetus. Multiple factors have been implicated in antibody transfer, but how these key regulators work together to elicit selective transfer is pertinent to engineering vaccines for mothers to optimally immunize their newborns. Here, we present the first quantitative mechanistic model to uncover the determinants of placental antibody transfer and inform personalized immunization approaches. We identified placental FcγRIIb expressed by endothelial cells as a limiting factor in receptor-mediated transfer, which plays a key role in promoting preferential transport of subclasses IgG1, IgG3, and IgG4, but not IgG2. Integrated computational modeling and in vitro experiments reveal that IgG subclass abundance, Fc receptor (FcR) binding affinity, and FcR abundance in syncytiotrophoblasts and endothelial cells contribute to inter-subclass competition and potentially inter- and intra-patient antibody transfer heterogeneity. We developed an in silico prenatal vaccine testbed by combining a computational model of maternal vaccination with this placental transfer model using the tetanus, diphtheria, and acellular pertussis (Tdap) vaccine as a case study. Model simulations unveiled precision prenatal immunization opportunities that account for a patient's anticipated gestational length, placental size, and FcR expression by modulating vaccine timing, dosage, and adjuvant. This computational approach provides new perspectives on the dynamics of maternal-fetal antibody transfer in humans and potential avenues to optimize prenatal vaccinations that promote neonatal immunity.

Investigating the impact of Sinopharm COVID-19 vaccination on antibody response in pregnant women and their newborns.

This study aims to investigate the levels of receptor-binding domain (RBD), spike, and neutralizing antibodies in pregnant women who received the Sinopharm vaccine and their newborns. A cross-sectional study was conducted at a tertiary center, Mashhad, Iran. We included 88 pregnant women who had received at least two doses of the Sinopharm vaccine. Maternal and umbilical cord blood samples taken at delivery were analyzed for antibodies using ELISA tests. Antibody levels did not vary significantly between women with two or three vaccine doses. Only 1.1% of mothers had undetectable levels of RBD antibodies, but detectable antibodies were observed in all newborns. A significant linear correlation was found between the levels of neutralizing antibodies (r = 0.7, p < 0.001) and RBD antibodies (r = 0.833, p < 0.001) in mothers and their newborns, but not for Spike antibodies (r = 0.214, p = 0.045). In mothers, high titers of antispike and RBD antibodies were observed at the time of delivery. The high titers of RBD and antispike antibodies were found in cord blood, suggesting potential neonatal immunity. Detectable levels of antibodies were found in both groups, regardless of the timing of vaccination. The Sinopharm vaccine generates detectable levels of antibodies in pregnant women, which are efficiently transferred to their newborns. The number of vaccine doses (two or three) did not significantly impact the levels of detectable antibodies. This underscores Sinopharm's potential efficacy in protecting pregnant women and their infants from COVID-19.

Ultra-High Temperature Treatment of Liquid Infant Formula, Systemic Immunity, and Kidney Development in Preterm Neonates.

Ready-to-feed liquid infant formulas (IFs) are increasingly being used for newborn preterm infants when human milk is unavailable. However, sterilization of liquid IFs by ultra-high temperature (UHT) introduces Maillard reaction products (MRPs) that may negatively affect systemic immune and kidney development. UHT-treated IF without and with prolonged storage (SUHT) are tested against pasteurized IF (PAST) in newborn preterm pigs as a model for preterm infants. After 5 days, blood leukocytes, markers of systemic immunity and inflammation, kidney structure and function are evaluated. No consistent differences between UHT and PAST pigs are observed. However, SUHT increases plasma TNFα and IL-6 and reduces neutrophils and in vitro response to LPS. In SUHT pigs, the immature kidneys show minor upregulation of gene expressions related to inflammation (RAGE, MPO, MMP9) and oxidative stress (CAT, GLO1), together with glomerular mesangial expansion and cell injury. The increased inflammatory status in SUHT pigs appears unrelated to systemic levels of MRPs. SUHT feeding may impair systemic immunity and affect kidney development in preterm newborns. The systemic effects may be induced by local gut inflammatory effects of MRPs. Optimal processing and length of storage are critical for UHT-treated liquid IFs for preterm infants.

Diverging Maternal and Cord Antibody Functions From SARS-CoV-2 Infection and Vaccination in Pregnancy.

Maternal immunity impacts the infant, but how is unclear. To understand the implications of the immune exposures of vaccination and infection in pregnancy for neonatal immunity, we evaluated antibody functions in paired peripheral maternal and cord blood. We compared those who in pregnancy received mRNA coronavirus disease 2019 (COVID-19) vaccine, were infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the combination. We found that vaccination enriched a subset of neutralizing activities and Fc effector functions that was driven by IgG1 and was minimally impacted by antibody glycosylation in maternal blood. In paired cord blood, maternal vaccination also enhanced IgG1. However, Fc effector functions compared to neutralizing activities were preferentially transferred. Moreover, changes in IgG posttranslational glycosylation contributed more to cord than peripheral maternal blood antibody functional potency. These differences were enhanced with the combination of vaccination and infection as compared to either alone. Thus, Fc effector functions and antibody glycosylation highlight underexplored maternal opportunities to safeguard newborns.

B-1 B Cell-Derived Natural Antibodies against N-Acetyl-d-Glucosamine Suppress Autoimmune Diabetes Pathogenesis.

Environmental factors and host microbiota strongly influence type 1 diabetes (T1D) progression. We report that neonatal immunization with group A Streptococcus suppresses T1D development in NOD mice by promoting clonal expansion of N-acetyl-d-glucosamine (GlcNAc)-specific B-1 B cells that recognize pancreatic β cell-derived Ags bearing GlcNAc-containing posttranslational modifications. Early exposure to Lancefield group A cell-wall carbohydrate Ags increased production of GlcNAc-reactive serum Abs and enhanced localization of innate-like GlcNAc-specific B cells to pancreatic tissue during T1D pathogenesis. We show that B-1 B cell-derived GlcNAc-specific IgM engages apoptosis-associated β cell Ags, thereby suppressing diabetogenic T cell activation. Likewise, adoptively transferring GlcNAc-reactive B-1 B cells significantly delayed T1D development in naive recipients. Collectively, these data underscore potentially protective involvement of innate-like B cells and natural Abs in T1D progression. These findings suggest that previously reported associations of reduced T1D risk after GAS infection are B cell dependent and demonstrate the potential for targeting the natural Ab repertoire in considering therapeutic strategies for T1D.

M2-polarized macrophages prevent preterm birth and improve neonatal survival and immunity

M2-polarized macrophages prevent preterm birth and improve neonatal survival and immunity

Pregnancy-induced transfer of pathogen-specific Tcells from mother to fetus in mice.

Neonatal health is determined by the transfer of maternal antibodies from the mother to the fetus. Besides antibodies, maternal cells cross the placental barrier and seed into fetal organs. Contrary to maternal antibodies, maternal microchimeric cells (MMc) show a high longevity, as they can persist in the offspring until adulthood. Recent evidence highlights that MMc leukocytes promote neonatal immunity against early-life infections in mice and humans. As shown in mice, this promotion of immunity was attributable to an improved fetal immune development. Besides this indirect effect, MMc may be pathogen-specific and thus, directly clear pathogen threats in the offspring postnatally. By using ovalbumin recombinant Listeria monocytogenes (LmOVA), we here provide evidence that OVA-specific T cells are transferred from the mother to the fetus, which is associated with increased activation of T cells and a milder course of postnatal infection in the offspring. Our data highlight that maternally-derived passive immunity of the neonate is not limited to antibodies, as MMc have the potential to transfer immune memory between generations.

SARS-CoV-2 vaccination, booster, and infection in pregnant population enhances passive immunity in neonates

The effects of heterogeneous infection, vaccination and boosting histories prior to and during pregnancy have not been extensively studied and are likely important for protection of neonates. We measure levels of spike binding antibodies in 4600 patients and their neonates with different vaccination statuses, with and without history of SARS-CoV-2 infection. We investigate neutralizing antibody activity against different SARS-CoV-2 variant pseudotypes in a subset of 259 patients and determined correlation between IgG levels and variant neutralizing activity. We further study the ability of maternal antibody and neutralizing measurements to predict neutralizing antibody activity in the umbilical cord blood of neonates. In this work, we show SARS-CoV-2 vaccination and boosting, especially in the setting of previous infection, leads to significant increases in antibody levels and neutralizing activity even against the recent omicron BA.1 and BA.5 variants in both pregnant patients and their neonates.

COVID-19 vaccine induced poor neutralization titers for SARS-CoV-2 omicron variants in maternal and cord blood.

Maternally derived antibodies are crucial for neonatal immunity. Understanding the binding and cross-neutralization capacity of maternal and cord antibody responses to SARS-CoV-2 variants following COVID-19 vaccination in pregnancy can inform neonatal immunity. Here we characterized the binding and neutralizing antibody profile at delivery in 24 pregnant individuals following two doses of Moderna mRNA-1273 or Pfizer BNT162b2 vaccination. We analyzed for SARS-CoV-2 multivariant cross-neutralizing antibody levels for wildtype Wuhan, Delta, Omicron BA1, BA2, and BA4/BA5 variants. In addition, we evaluated the transplacental antibody transfer by profiling maternal and umbilical cord blood. Our results reveal that the current COVID-19 vaccination induced significantly higher RBD-specific binding IgG titers in cord blood compared to maternal blood for both the Wuhan and Omicron BA1 strain. Interestingly, the binding IgG antibody levels for the Omicron BA1 strain were significantly lower when compared to the Wuhan strain in both maternal and cord blood. In contrast to the binding, the Omicron BA1, BA2, and BA4/5 specific neutralizing antibody levels were significantly lower compared to the Wuhan and Delta variants. It is interesting to note that the BA4/5 neutralizing capacity was not detected in either maternal or cord blood. Our data suggest that the initial series of COVID-19 mRNA vaccines were immunogenic in pregnant women, and vaccine-elicited binding antibodies were detectable in cord blood at significantly higher levels for the Wuhan and Delta variants but not for the Omicron variants. Interestingly, the vaccination did not induce neutralizing antibodies for Omicron variants. These results provide novel insight into the impact of vaccination on maternal humoral immune response and transplacental antibody transfer for SARS-CoV-2 variants and support the need for bivalent boosters as new variants emerge.

The Neonatal Immune System and Respiratory Pathogens.

Neonates are more susceptible to some pathogens, particularly those that cause infection in the respiratory tract. This is often attributed to an incompletely developed immune system, but recent work demonstrates effective neonatal immune responses to some infection. The emerging view is that neonates have a distinctly different immune response that is well-adapted to deal with unique immunological challenges of the transition from a relatively sterile uterus to a microbe-rich world, tending to suppress potentially dangerous inflammatory responses. Problematically, few animal models allow a mechanistic examination of the roles and effects of various immune functions in this critical transition period. This limits our understanding of neonatal immunity, and therefore our ability to rationally design and develop vaccines and therapeutics to best protect newborns. This review summarizes what is known of the neonatal immune system, focusing on protection against respiratory pathogens and describes challenges of various animal models. Highlighting recent advances in the mouse model, we identify knowledge gaps to be addressed.

Association of Umbilical Cord Igg Covid Antibody Levels with Maternal Factors

Background: The transmission of SARS-CoV-2 from mother to fetus and the development of protective antibodies in newborns are critical aspects of maternal and neonatal care during the COVID-19 pandemic. Understanding the association between umbilical cord IgG COVID-19 antibody levels and maternal factors, including gestational age of acquiring infection, COVID-19 clinical category, and immunization status, can provide insights into neonatal immunity and guide strategies for optimizing maternal and neonatal care.&#x0D; Methods: This study aimed to investigate the association between umbilical cord IgG COVID-19 antibody levels and maternal factors in a cohort of pregnant women with confirmed SARS-CoV-2 infection. Maternal data, including gestational age of acquiring infection, COVID-19 clinical category, and immunization status, were collected. Umbilical cord blood samples were obtained at delivery, and IgG COVID-19 antibody levels were measured using standardized assays. Statistical analyses were performed to assess the associations between maternal factors and neonatal antibody levels.&#x0D; Results: Preliminary results showed that gestational age of acquiring infection was positively associated with umbilical cord IgG COVID-19 antibody levels (p&lt;0.001). Neonates born to mothers infected in the third trimester had significantly higher antibody levels compared to those infected in the first or second trimesters. Additionally, there was a significant positive correlation between COVID-19 clinical category and umbilical cord IgG antibody levels, with more severe maternal illness associated with higher neonatal antibody levels. Maternal immunization status also demonstrated a positive association with umbilical cord IgG COVID-19 antibody levels, indicating that vaccinated mothers had higher levels of antibodies transferred to their infants.&#x0D; Conclusion: This study highlights the association between umbilical cord IgG COVID-19 antibody levels and maternal factors, including gestational age of acquiring infection, COVID-19 clinical category, and immunization status. The findings suggest that infection in the third trimester, more severe maternal illness, and maternal immunization are associated with higher levels of neonatal antibodies. These results have important implications for understanding neonatal immunity and guiding maternal and neonatal care during the COVID-19 pandemic. Further research with larger cohorts is warranted to validate these findings and inform evidence-based strategies for optimizing maternal and neonatal outcomes.

Immune responses following neonatal vaccination with conserved F4 fragment of VtaA proteins from virulent Glaesserella parasuis adjuvanted with CAF®01 or CDA

Glaesserella parasuis is a Gram-negative bacterium that colonizes the upper airways of swine, capable of causing a systemic infection called Glässer’s disease. This disease is more frequent in young post-weaning piglets. Current treatments against G. parasuis infection are based on the use of antimicrobials or inactivated vaccines, which promote limited cross-protection against different serovars. For this reason, there is an interest in developing novel subunit vaccines with the capacity to confer effective protection against different virulent strains. Herein, we characterize the immunogenicity and the potential benefits of neonatal immunization with two different vaccine formulations based on the F4 polypeptide, a conserved immunogenic protein fragment from the virulence-associated trimeric autotransporters of virulent G. parasuis strains. With this purpose, we immunized two groups of piglets with F4 combined with cationic adjuvant CAF®01 or cyclic dinucleotide CDA. Piglets immunized with a commercial bacterin and non-immunized animals served as control groups. The vaccinated piglets received two doses of vaccine, at 14 days old and 21 days later. The immune response induced against the F4 polypeptide varied depending on the adjuvant used. Piglets vaccinated with the F4+CDA vaccine developed specific anti-F4 IgGs, biased towards the induction of IgG1 responses, whereas no anti-F4 IgGs were de novo induced after immunization with the CAF®01 vaccine. Piglets immunized with both formulations displayed balanced memory T-cell responses, evidenced upon in vitro re-stimulation of peripheral blood mononuclear cells with F4. Interestingly, pigs immunized with F4+CAF®01 controlled more efficiently a natural nasal colonization by a virulent serovar 4 G. parasuis that spontaneously occurred during the experimental procedure. According to the results, the immunogenicity and the protection afforded by F4 depend on the adjuvant used. F4 may represent a candidate to consider for a Glässer‘s disease vaccine and could contribute to a better understanding of the mechanisms involved in protection against virulent G. parasuis colonization.

The hormonal physiology of immune components in breast milk and their impact on the infant immune response

During pregnancy, the maternal body undergoes a considerable transformation regarding the anatomy, metabolism, and immune profile that, after delivery, allows for protection and nourishment of the offspring via lactation. Pregnancy hormones are responsible for the development and functionality of the mammary gland for breast milk production, but little is known about how hormones control its immune properties. Breast milk composition is highly dynamic, adapting to the nutritional and immunological needs that the infant requires in the first months of life and is responsible for the main immune modeling of breastfed newborns. Therefore, alterations in the mechanisms that control the endocrinology of mammary gland adaptation for lactation could disturb the properties of breast milk that prepare the neonatal immune system to respond to the first immunologic challenges. In modern life, humans are chronically exposed to endocrine disruptors (EDs), which alter the endocrine physiology of mammals, affecting the composition of breast milk and hence the neonatal immune response. In this review, we provide a landscape of the possible role of hormones in the control of passive immunity transferred by breast milk and the possible effect of maternal exposure to EDs on lactation, as well as their impacts on the development of neonatal immunity.

The protective role of maternal genetic immunization on maternal-fetal health and welfare.

Pregnancy is a critical period associated with alterations in physiologic, biologic, and immunologic processes, which can affect maternal-fetal health through development of several infectious diseases. At birth, neonates have an immature immune system that makes them more susceptible to severe viral infections and diseases. For this reason, different maternal nutritional and immunization interventions have been used to improve the immune and health status of the mother and her neonate through passive immunity. Here, we reviewed the protective role of maternal immunization with different types of vaccines, especially genetic vaccines, during pregnancy in maternal-fetal health, immune response, colostrum quality, immune response, and anti-oxidative status. For this purpose, we have used different scientific databases (PubMed and Google Scholar) and other official web pages. We customized the search period range from the year 2000 to 2023 using the key words "maternal immunization" OR "gestation period/pregnancy" OR "genetic vaccination" OR "maternal-fetal health" OR "micronutrients" OR "neonatal immunity" "oxidative stress" OR "colostrum quality". The evidence demonstrated that inactivated or killed vaccines produced significant immune protection in the mother and fetus. Furthermore, most recent studies have suggested that the use of genetic vaccines (mRNA and DNA) during pregnancy is efficient at triggering the immune response in mother and neonate without the risk of undesired pregnancy outcomes. However, factors such as maternal redox balance, nutritional status, and the timing of immunization play essential roles in regulating immune response inflammatory status, antioxidant capacity, and the welfare of both the pregnant mother and her newborn.

Maternal HIV infection drives altered placental Mtb-specific antibody transfer.

Placental transfer of maternal antibodies is essential for neonatal immunity over the first months of life. In the setting of maternal HIV infection, HIV-exposed uninfected (HEU) infants are at higher risk of developing severe infections, including active tuberculosis (TB). Given our emerging appreciation for the potential role of antibodies in the control of Mycobacterium tuberculosis (Mtb), the bacteria that causes TB, here we aimed to determine whether maternal HIV status altered the quality of Mtb-specific placental antibody transfer. Antigen-specific antibody systems serology was performed to comprehensively characterize the Mtb-specific humoral immune response in maternal and umbilical cord blood from HIV infected and uninfected pregnant people in Uganda. Significant differences were noted in overall antibody profiles in HIV positive and negative maternal plasma, resulting in heterogeneous transfer of Mtb-specific antibodies. Altered antibody transfer in HIV infected dyads was associated with impaired binding to IgG Fc-receptors, which was directly linked to HIV viral loads and CD4 counts. These results highlight the importance of maternal HIV status on antibody transfer, providing clues related to alterations in transferred maternal immunity that may render HEU infants more vulnerable to TB than their HIV-unexposed peers.

Novel murine model reveals an early role for pertussis toxin in disrupting neonatal immunity to Bordetella pertussis

Abstract The increased susceptibility of neonates to some pathogens has previously been attributed to an underdeveloped immune system. More recent data suggest neonates have effective protection against most pathogens but are particularly susceptible to those that target immune functions specific to neonates. Bordetella pertussis (Bp), the causative agent of “whooping cough”, causes more serious disease in infants attributed to its production of pertussis toxin (PTx). Problematically, the rapid development of adult immunity in mice has confounded our ability to study the interaction of this agent with neonatal immune components, such as virtual memory T cells which are prominent prior to the maturation of the thymus. Here, we examine the rapid change in susceptibility of young mice and define a period from five- to eight-days-old during which mice are much more susceptible to Bp than mice even a few days older. These more narrowly defined “neonatal” mice display significantly increased susceptibility to wild type Bp but very rapidly and effectively respond to and control Bp lacking PTx, more rapidly even than adult mice. The clearance of the PTx mutant correlates with the early accumulation of neutrophils and T cells and suggests a role for PTx in disrupting their accumulation. These results define an early age of extreme susceptibility to Bp, and demonstrate that the neonatal response can be more efficient than the adult response in eliminating bacteria from the lungs, but these neonatal functions are substantially blocked by PTx. This refined definition of “neonatal” mice may be useful in the study of other pathogens that predate neonates, and PTx may prove a particularly valuable tool for probing the poorly understood neonatal immune system. This work was supported by grants AI156293 and AI159347 of the National Institutes of Health to Eric Harvill and AI139449 of the National Institutes of Health to Nancy Manley.

IL-6 suppresses vaccine responses in neonatal mice by enhancing IL-2 activity on T follicular helper cells

Abstract The inability of neonates to develop CD4+CXCR5+PD-1+ T follicular helper (TFH) cells contributes to their weak vaccine responses. In previous studies, we measured diminished IgG responses when IL-6 was co-injected with a pneumococcal conjugate vaccine (PCV) in neonatal mice. This is in sharp contrast to adults, where IL-6 improves vaccine responses by downregulating the expression of IL-2Rβ on TFH cells and protecting them from the inhibitory effect of IL-2. In this study, we found that splenic IL-6 levels rapidly increased in both adult and neonatal mice following immunization, but the increase in neonatal mice was significantly more than that of adult mice. Moreover, immunized neonatal TFH cells expressed significantly more IL-2 as well as its receptors, IL-2Rα and IL-2Rβ, than the adult cells. Remarkably, IL-6 co-injection with PCV vaccine further increased the production of IL-2 and the expression of its receptors by neonatal TFH cells, whereas excess IL-6 had totally opposite effect in immunized adult mice. Underscoring the role of IL-6 in activating the IL-2 mediated suppression of vaccine responses, immunization of IL-6 knock-out neonates led to improved antibody responses accompanied by expanded TFH cells as well as lower levels of IL-2 and IL-2 receptors on TFH cells. Moreover, CpG containing PCV improved TFH response in neonates by suppressing the expression of IL-2 receptors on TFH cells and inhibiting IL-2 activity. These findings unveil age-specific differences in IL-6 mediated vaccine responses and highlight the need to consider age-related immunobiological attributes in designing vaccines. This study was funded by US FDA, Perinatal Health Center of Excellence (PHCE) grant to Mustafa Akkoyunlu as well as intramural grants from US FDA.

Fecal excretion of Campylobacter jejuni by young dairy calves and the relationship with neonatal immunity and personality traits.

Zoonotic pathogens in bovine herds are major concerns for human and animal health, but their monitoring in animals can be challenging in the absence of clinical signs. Our objective was to determine the association between fecal excretion of C. jejuni, neonatal immunity and personality traits of calves. Forty-eight dairy calves were reared in three indoor pens from birth to four weeks of life. Microbial analyses of the fecal samples collected weekly revealed that the proportion of calves naturally contaminated with C. jejuni in each pen reached 70% after three weeks of life. High (>16 g.l-1) levels of IgG levels in the serum of neonatal calves were negatively (P= 0.04) associated with fecal detection of C. jejuni over the trial period. Calves that spent more time interacting with a novel object tended to be positive (P=0.058) for C. jejuni. Overall, the findings indicate that the immunity of neonatal dairy animals and possibly the animal's behavior may contribute to the fecal shedding of C. jejuni.