Transfer Of Maternal Antibodies Research Articles

Immune response induced by a Streptococcus suis multi-serotype autogenous vaccine used in sows to protect post-weaned piglets

Streptococcus suis is a bacterial pathogen that causes important economic losses to the swine industry worldwide. Since there are no current commercial vaccines, the use of autogenous vaccines applied to gilts/sows to enhance transfer of passive immunity is an attractive alternative to protect weaned piglets. However, there is no universal standardization in the production of autogenous vaccines and the vaccine formulation may be highly different among licenced manufacturing laboratories. In the present study, an autogenous vaccine that included S. suis serotypes 2, 1/2, 5, 7 and 14 was prepared by a licensed laboratory and administrated to gilts using a three-dose program prior to farrowing. The antibody response in gilts as well as the passive transfer of antibodies to piglets was then evaluated. In divergence with previously published data with an autogenous vaccine produced by a different company, the increased response seen in gilts was sufficient to improve maternal antibody transfer to piglets up to 5 weeks of age. However, piglets would still remain susceptible to S. suis disease which often appears during the second part of the nursery period. Vaccination did not affect the shedding of S. suis (as well as that of the specific S. suis serotypes included in the vaccine) by either gilts or piglets. Although all antibiotic treatments were absent during the trial, the clinical protective effect of the vaccination program with the autogenous vaccine could not be evaluated, since limited S. suis cases were present during the trial, confirming the need for a complete evaluation of the clinical protection that must include laboratory confirmation of the aetiological agent involved in the presence of S. suis-associated clinical signs. Further studies to evaluate the usefulness of gilt/sow vaccination with autogenous vaccines to protect nursery piglets should be done.

Myasthenia gravis-Gender aspects and family planning

There is evidence that gender-specific differences can influence the diagnostics, treatment and long-term disease course of myasthenia gravis (MG). In women the diagnosis is often made during childbearing age. Gender-specific differences in MG and relevant aspects in routine clinical practice are presented. In addition, current studies on family planning, pregnancy and childbirth in MG are highlighted and treatment recommendations are derived. Narrative literature review. In addition to sociodemographic data, gender-specific differences encompass clinical as well as paraclinical factors, such as disease severity and antibody status. With few exceptions pregnancy is possible with good maternal and neonatal outcome. During pregnancy and peripartum, children of MG patients should be closely monitored for early detection and treatment of potential syndromes caused by diaplacental transfer of maternal antibodies. Gender-specific factors can influence the course of MG. Adequate medical counselling and multidisciplinary collaboration are essential for MG patients who wish to have children.

Maternal-driven immune education in offspring.

Maternal environmental exposures, particularly during gestation and lactation, significantly influence the immunological development and long-term immunity of offspring. Mammalian immune systems develop through crucial inputs from the environment, beginning in utero and continuing after birth. These critical developmental windows are essential for proper immune system development and, once closed, may not be reopened. This review focuses on the mechanisms by which maternal exposures, particularly to pathogens, diet, and microbiota, impact offspring immunity. Mechanisms driving maternal-offspring immune crosstalk include transfer of maternal antibodies, changes in the maternal microbiome and microbiota-derived metabolites, and transfer of immune cells and cytokines via the placenta and breastfeeding. We further discuss the role of transient maternal infections, which are common during pregnancy, in providing tissue-specific immune education to offspring. We propose a "maternal-driven immune education" hypothesis, which suggests that offspring can use maternal encounters that occur during a critical developmental window to develop optimal immune fitness against infection and inflammation.

Seroprevalence and risk factors associated with Theileria parva infection among calves in Narok County, Kenya

Background and Aim: East Coast fever (ECF), caused by Theileria parva, is a devastating disease that causes significant economic losses to cattle production in sub-Saharan Africa. Prevention and control of ECF are challenging in pastoral settings due to inadequate epidemiological information. This study aimed to estimate the seroprevalence and risk factors associated with T. parva infection among calves in different production systems to help design appropriate control interventions. Materials and Methods: Blood samples were collected from 318 calves and tested using an indirect enzyme-linked immunosorbent assay targeting antibodies against polymorphic immunodominant molecules found on the surface of T. parva. Information on calf characteristics and management practices was also collected during sampling. Descriptive statistics and logistic regression were used to analyze potential risk factors, such as age and acaricide application, where p < 0.05 was considered significant Results: Of the 318 calves sampled, 41 (12.89%) were positive for T. parva, with a higher proportion in pastoral systems (36.58%) than in mixed farming systems (34.10%) and agropastoral systems (29.27%). From univariate analysis, calf age (p = 0.002), body weight (p = 0.001), suckling status (p = 0.026), rectal temperature (p = 0.06), calves on pasture (p = 0.022), other feeds (p = 0.004), feed grown within the farm (p = 0.004), acaricide application (p = 0.001), and acaricide application frequency (p = 0.001) were significantly associated with seropositivity. However, calf age (odds ratio [OR], 0.96; 95% confidence interval [CI], 0.91-0.99; p = 0.04), other feeds (OR, 8.82; 95% CI, 1.74-44.63; p = 0.009), and suckling status (OR, 0.38; 95% CI, 0.15-0.99; p = 0.05) were significantly associated with T. parva infection in the multivariable mixed logistic model. Conclusion: T. parva is circulating in young calves in the study area (and possibly in cattle populations due to maternal transfer of antibodies to the calves). There is a need for molecular surveillance to determine the presence and burden of T. parva infection. Keywords: calves, risk factors, seroprevalence, Theileria parva.

Analysis of the transplacental transmission of SARS CoV-2 virus and antibody transfer according to the gestational age at maternal infection

To quantify transplacental transmission of SARS-CoV-2 virus and antibody transfer in pregnant women and their newborns according to the gestational age at maternal infection. A prospective observational multicenter study including pregnant women with a positive RT-PCR or a positive serology for SARS-CoV-2 and compatible symptoms, from April to December 2020, in 11 French maternities. The study was designed to obtain a systematic collection of mother-infant dyad’s samples at birth. SARS-CoV-2 viral load was measured by RT-PCR. IgG and IgM antibodies against the SARS-CoV-2 spike protein were measured by enzyme-linked immunosorbent assay. Antibody concentrations and transplacental transfer ratios were analyzed according to the gestational age at maternal infection. The primary outcome was the rate of SARS CoV-2 materno-fetal transmission at birth. The secondary outcome was the quantification of materno-fetal antibody transfer. Maternal and neonatal outcomes at birth were additionally assessed. Among 165 dyads enrolled, one congenital infection was confirmed {n = 1 (0.63%) IC95% [0.02%; 3.48%]}. The average placental IgG antibody transfer ratio was 1.27 (IC 95% [0.69–2.89]). The transfer ratio increased with increasing time between the onset of maternal infection and delivery (P Value = 0.0001). Maternal and neonatal outcomes were reassuring. We confirmed the very low rate of SARS-CoV-2 transplacental transmission (< 1%). Maternal antibody transfer to the fetus was more efficient when the infection occurred during the first and second trimester of pregnancy.

VEDOLIZUMAB DOES NOT ALTER IMMUNOGLOBULIN LEVELS IN BREASTMILK OF MOTHERS WITH IBD

Abstract Diarrheal diseases are a major cause of infant mortality worldwide. Breastfeeding helps prevent such diseases by passive transfer of maternal antibodies against gastrointestinal pathogens previously encountered by the mother. The antibody secreting cells (ASC) that populate the lactating mammary gland (LMG) are educated in gastrointestinal lymphoid tissues, thus they express integrin a4b7. To recruit these ASC, the LMG expresses MAdCAM-1 and CCL28. Vedolizumab (vedo) blocks a combinatorial epitope on integrin a4b7, interfering with lymphocyte recruitment to the gut. Given the shared homing determinants between the gut and LMG, we investigated whether vedo might interfere with ASC trafficking to the LMG, therefore decreasing immunoglobulin (Ig) levels in breast milk. We measured Ig levels by ELISA in cryopreserved breast milk from mothers enrolled in Mommy’s Milk biorepository at the University of California, San Diego without and with Ulcerative Colitis(UC) or Crohn’s Disease(CD) and lactating mothers with UC and CD treated with vedo for more than 18 months. Milk samples were collected between 1 month and 15.45 months after childbirth. The levels of secretory IgA (SIgA) in breast milk of mothers without IBD (n=45) was not different from those of mothers with CD not on vedo (n=15) (301 ± 147 ug/mL vs. 322 ± 207 ug/mL). However, milk SIgA from mothers with UC not on vedo (n=7) were lower than non-IBD controls (213 ± 149 ug/mL vs. 301 ± 147ug/mL, p&amp;lt;0.01). We then compared milk SIgA from patients with CD and UC treated with vedo (CD: n= 9; 256 ± 80ug/mL, UC: n=10; 283 ± 87 ug/mL) with those from non-IBD controls (n=45; 301 ± 147ug/mL) and found no differences. Similarly, SIgA levels were not different between CD with or without vedo (256 ± 80 ug/mL vs. 322 ± 207 ug/mL) and as compared with non-IBD controls SIgA in patients with UC with vedo were unexpectedly higher than UC without vedo (283 ±87 ug/mL vs 213 ± 149 ug/mL, p&amp;lt;0.05). The levels of secretory IgM (SIgM) in milk were not different between mothers with UC or CD treated with vedo compared with non-IBD controls (65 ± 34 ug/mL, 69 ± 32 ug/mL, and 56 ± 37 ug/mL, respectively). Similarly, no significant difference was seen between patients with UC or CD not treated with vedo compared with the non-IBD controls (58±26 ug/mL, and 46 ± 24 ug/mL respectively). We conclude that vedo does not reduce SIgA nor SIgM levels in lactating mothers with IBD. We speculate that the higher SIgA in patients with UC treated with vedo is due to the small sample size. Vedo does not interfere with passive immunity during the lactation period, thus ASC must be able to use another integrin to arrest on microvessels of the LMG during the final stages of pregnancy.

Effective and safe transfer of maternal antibodies persisting two months postpartum following maternal immunization with different doses of recombinant pertussis-containing vaccines

IntroductionRecombinant acellular pertussis (ap) vaccines containing genetically inactivated pertussis toxin (PTgen) and filamentous hemagglutinin (FHA) with or without tetanus (TT) and diphtheria (DT) vaccines (Td) were found safe and immunogenic in non-pregnant and pregnant women. We report here maternal antibody transfer and safety data in mothers and neonates. MethodsThis is the follow up of a phase 2 trial in 2019 among 400 pregnant women who randomly received one dose of recombinant pertussis-only vaccine containing 1 µg PTgen and 1 µg FHA (ap1gen), or Td combined with ap1gen (Tdap1gen), or with 2 µg PTgen and 5 µg FHA (Tdap2gen), or with 5 µg PTgen and 5 µg FHA (TdaP5gen, Boostagen®, BioNet, Thailand) or chemically-inactivated acellular pertussis comparator (Tdap8chem, Boostrix™, GSK, Belgium), either in the second or third trimester of gestation. IgG against PT, FHA, TT and DT were assessed by ELISA, PT-neutralizing antibodies (PTNA) by Chinese Hamster Ovary cell assay and safety outcomes at delivery in mothers and at birth. ResultsAnti-PT and anti-FHA geometric mean concentration (GMC) ratio between infants at birth and mothers at delivery was above 1 in all groups. PT GMC in infants at birth were ≥30 IU/mL in all groups with the highest titers in infants found in TdaP5gen group at birth (118.8 [95% CI 93.9–150.4]). At 2 months, PT GMC ratio to Tdap8chem (98.75% CI) was significantly higher for TdaP5gen (2.6 [1.7–4.0]) and comparable for other recombinant vaccines. No difference in PTNA titers at birth was observed between all groups nor between time of vaccination. Adverse events were comparable in all vaccine groups. ConclusionsBioNet licensed (TdaP5gen and Tdap2gen) and candidate vaccines (Tdap1gen and ap1gen) when given to pregnant women in the second or third trimester of gestation are safe and have induced passive pertussis immunity to infants.

Maternal Seroprevalence and Placental Transfer of COVID-19 Antibodies in Pregnancy: A Hospital-Based Study.

Coronavirus disease 2019 (COVID-19) is a relatively new disease with high morbidity and mortality.Information about the prevalence of infections in pregnancy could help identify herd immunity, project epidemics, and decide policy guidelines. The aim of this study was to determine the infection susceptibility risk of COVID-19 in pregnancy, to determine the prevalence of COVID-19 antibodies (IgG & IgM), and to evaluate the determinants of COVID-19 antibody positivity in pregnancy. This was an analytical cross-sectional study involving 258 consenting pregnant women recruited at Irrua Specialist Teaching Hospital, Edo State, Nigeria. Of these, 179 participants were recruited from the antenatal clinic, and 79 from the gynecology emergency unit. A structured questionnaire was administered at baseline. Venous blood was obtained at enrolment to test for total antibodies using ELISA. A nasopharyngeal swab was simultaneously obtained for COVID-19 PCR for all participants. Umbilical cord blood was taken after delivery in those who had positive serology. Socio-demographic variables and clinical presentation of respondents were considered as exposure variables, and this was cross-tabulated with outcome variables in bivariate analysis using chi-square with a level of significance at a P-value less than 0.05. Variables in bivariate analysis of chi-square that have a P-value less than 0.2 were entered into a logistic regression using multivariate logistic models. The study detected active COVID-19 infections among 7.4% (19/258) of the study participants. The study demonstrated a seroprevalence of COVID-19 antibodies in 62.4% (161/258) of the participants at recruitment and showed a strong correlation between working in the healthcare setting and living in an urban environment. Our study also reported 5.3% (8/152) of cord blood antibody positivity among study participants. The concentration of maternal immunoglobulin strongly and positively correlated with cord blood seropositivity. Prevalence estimates are an underestimate of the actual proportion of pregnant women with prior COVID-19 exposure as observed in the study discrepancy of confirmed PCR infection and evidence of previous infection from serology. The study also highlighted a low efficiency of placental transfer of COVID-19 antibodies at birth among those who were seropositive at baseline and showed that maternal antibody levels play an important role in determining the efficiency of placenta transfer of COVID-19 antibodies in pregnancy.

916. The Transfer of Maternal Antibodies and Dynamics of Maternal and Natural Infection-induced Antibodies against RSV in Children: A Longitudinal Cohort Study

Abstract Background Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infectious disease in children globally. Transplacental-acquired antibodies are essential in protecting infants during the initial months of their life. This study assessed the efficacy of transferring maternal RSV prefusion protein (pre-F) IgG antibodies via the placenta and reported the dynamics of maternal and natural infection-induced antibodies in children. Methods A longitudinal mother-neonate pairs cohort was started enrolled in southern China in the autumn of 2013. 660 mother-neonate pairs were included in this study. Both cord blood from neonates and venous blood from mothers at delivery were obtained. The children were followed up and blood samples were collected at ages 2, 4, 6, 12, 24, and 36 months, as well as at 6-8 years (Figure 1). RSV-specific pre-F IgG antibodies were identified by the enzyme-linked immunosorbent assay method. The maternal antibody transfer efficacy, decay of maternal antibodies, age-specific antibody level, and seroprevalence were estimated. Results All neonates acquired RSV pre-F IgG antibodies from their mothers. We found a significant correlation between maternal and neonatal antibody titers (ρ=0.86, P&amp;lt; 0.001). The average RSV pre-F IgG antibody titers were higher in cord blood than in maternal blood, with a mean transfer ratio of maternal antibodies of 1.48 (95%CI: 1.44-1.52) (Figure 2). Maternal antibody levels in neonates declined rapidly, with a half-life of 1.4 months. The lowest point of antibodies occurred at 11 months of age, followed by titer increases due to natural RSV infection, and approximately 50% of the children seroconverted at the age of 41.5 months.Figure 2(A) Correlation between neonatal and maternal antibody titer. (B) Transfer ratio with maternal antibody titers. The top orange density plots maternal antibody titers, and the right plots neonatal antibody titers. Conclusion Efficient transfer of RSV maternal antibodies to neonates was observed. As maternal antibodies wane, the seropositive infants gradually reduce to the lowest in the first year of life. After that, the infant’s immune system develops and naturally acquired immunity due to infection. Our findings will optimize future strategies for both vaccine and long-term prophylactic monoclonal antibodies to target RSV pre-F protein. Disclosures Hongjie Yu, PhD, GlaxoSmithKline: Grant/Research Support|Roche: Grant/Research Support|Sanofi: Grant/Research Support|SINOVAC: Grant/Research Support

467. Maternal Antibody and Placental Transfer Increases with Hybrid Immunity Against SARS-CoV-2 but Transferred Antibody is Qualitatively Different

Abstract Background Defining the magnitude and quality of antibodies induced by infection and vaccination for SARS-CoV-2 during pregnancy and that cross the placenta can improve strategies to protect both mothers and infants. Methods Maternal peripheral and neonatal cord blood were collected from participants enrolled in a prospective longitudinal cohort study, the Epidemiology, Immunology, and Clinical Characteristics of pathogens with pandemic potential (EPICC), after presenting to a military treatment facility between March 2020 and March of 2022 with either COVID-19 or receipt of the COVID-19 vaccine. SARS-CoV-2 spike-specific IgG and neutralizing titers (NT) were measured with a multiplex microsphere immunoassay and a pseudovirus assay, respectively. Antibody dependent cellular cytotoxicity (ADCC), antibody dependent cellular phagocytosis (ADCP) and opsonization were measured with cell and bead-based assays. Results During the study period 20 pregnant participants were enrolled. Paired biospecimens (maternal blood/cord blood) were collected near birth from 17; 11 had a history of SARS-CoV-2 infection and 6 had both infection and received the BNT162b2 vaccine during pregnancy. The average anti-spike IgG at time of birth from mothers who were infected versus infected and vaccinated during pregnancy was 165.5 and 2592.7 BAU/ml, respectively (p=0.006). Average NT titers in infected versus infected and vaccinated mothers were 131.7 and 971.5 IC50, respectively (p = 0.0001). Anti-spike IgG and NT were not significantly different within dyads. Interestingly, ADCC was generally higher in newborn cord blood compared to maternal peripheral blood by 2.5-fold in both groups, while ADCP and opsonization was not. Conclusion Our study showed that hybrid immunity, comprised of infection and vaccination during pregnancy, increased the total magnitude and neutralizing potential of anti-SARS-CoV-2 antibodies in mothers and infants. Both hybrid immunity and isolated infection resulted in an increased transfer of ADCC activity across the placenta. Hybrid immunity is now common and determining the effect on maternal antibody levels and the characteristics of those antibodies can help inform maternal immunization strategies and protocols. Disclosures Julia Rozman, BS, AstraZeneca: TBD Mark P. Simons, PhD, AstraZeneca: The IDCRP and HJF were funded to conduct an unrelated phase III COVID-19 monoclonal antibody immunoprophylaxis trial as part of US Govt COVID Response David Tribble, MD, DrPH, AstraZeneca: The IDCRP and HJF were funded to conduct an unrelated phase III COVID-19 monoclonal antibody immunoprophylaxis trial as part of US Govt COVID response Timothy Burgess, MD, MPH, AstraZeneca: The IDCRP and the Henry M. Jackson Foundation (HJF) were funded to conduct an unrelated phase III COVID-19 monoclonal antibody immunoprophylaxis trial Simon Pollett, MBBS, AstraZeneca: The IDCRP and the Henry M. Jackson Foundation (HJF) were funded to conduct an unrelated phase III COVID-19 monoclonal antibody immunoprophylaxis trial

Maternal mRNA COVID-19 Vaccination During Pregnancy and Delta or Omicron Infection or Hospital Admission in Infants: Test Negative Design Study

(BMJ. 2023;380:e074035) Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) rates are higher in infants than in older children. Passive immunity has been shown to help prevent other infections, such as pertussis, in infants through the transfer of maternal antibodies following vaccination during pregnancy. SARS-CoV-2 antibodies are found to be present in breastmilk, umbilical cord blood, and infant serum specimens following maternal vaccination during pregnancy and infection, and emerging research suggests maternal COVID-19 vaccination reduces infant infection and hospital admission rates. This study aimed to determine whether maternal vaccination during pregnancy with 2 primary doses or 2 primary doses plus booster of the mRNA COVID-19 vaccine series reduces the infection of omicron and delta SARS-CoV-2 and hospital admission of infants within 6 months following delivery.

Alloimmune hemolytic disease of the fetus and newborn: genetics, structure, and function of the commonly involved erythrocyte antigens.

Hemolytic disease of the fetus and newborn (HDFN) can occur when a pregnant woman has antibody directed against an erythrocyte surface antigen expressed by her fetus. This alloimmune disorder is restricted to situations where transplacental transfer of maternal antibody to the fetus occurs, and binds to fetal erythrocytes, and significantly shortens the red cell lifespan. The pathogenesis of HDFN involves maternal sensitization to erythrocyte "non-self" antigens (those she does not express). Exposure of a woman to a non-self-erythrocyte antigen principally occurs through either a blood transfusion or a pregnancy where paternally derived erythrocyte antigens, expressed by her fetus, enter her circulation, and are immunologically recognized as foreign. This review focuses on the genetics, structure, and function of the erythrocyte antigens that are most frequently involved in the pathogenesis of alloimmune HDFN. By providing this information we aim to convey useful insights to clinicians caring for patients with this condition.

Neutralizing anti-polio antibody titre in newborn babies in post-polio eradication period in Nigeria

BackgroundAccording to Polio Eradication and Endgame Strategic Plan 2019-2023 (PEESP), countries that achieved wild polio elimination is expected to replace oral polio vaccine (OPV) which has a risk of vaccine-derived poliovirus, Inactivated Polio Vaccine (IPV). It is important to determine the earliest time in the age of a child at which IPV could be introduced into the country’s routine immunization schedule for effectiveness especially as it concerns neutralizing effect of trans-placental transmitted antibodies which usually does not affect OPV. In this study, the level of poliovirus neutralizing antibody titre among neonates at birth was evaluated. MethodsA cross-sectional study of mother-baby pair. The serum level of the neutralizing Poliovirus antibody IgG titre was done by the Enzyme Linked Immunosorbent Assay (ELISA) technique. ResultsThere was 100% transfer of maternal passive antibodies to their babies. The mean poliovirus antibody titre among neonates was 21.8 IU/L which was above the neutralizing titre level. Most (85.7%) babies antibody level correlate positively with that of their mothers. ConclusionThe transferred maternal antibodies to the babies are still very high at birth, and capable of dampening the immunity of IPV if introduced early. Programme managers should evaluate the impact and benefit of given booster dose of IPV to pregnant mothers to increase the titre level in their babies. This will be very necessary when the OPV is withdrawn from the immunization schedule.

Maternal antibody transfer rate of vaccination against SARS-CoV-2 before or during early pregnancy and its protective effectiveness on offspring.

This study focuses on maternal antibody transfer following vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) before or during early pregnancy and its potential protective effects on infants, providing scientific evidence for vaccination strategies. This prospective study tested the samples for SARS-CoV-2 IgG antibody titers and neutralizing capacity and tracked the infections after birth. Perform multivariate analysis of factors influencing antibody transfer rate, newborn antibody titers, and infant infection. Total 87.1% (122/140) women received coronavirus disease 2019 (COVID-19) vaccine before or during early pregnancy, and 28 of them had breakthrough infection. The maternal and neonatal IgG positive rates at delivery were 60.7% (85/140) and 60.8% (87/143), respectively. A positive correlation was found between neonatal and maternal IgG antibody titers. Compared with the median IgG antibody transfer rate of infected pregnant women, that of vaccinated but not infected pregnant women was higher (1.21 versus: 1.53 [two doses], 1.71 [three doses]). However, neonatal IgG antibodies were relatively low (174.91 versus: 0.99 [two doses], 8.18 [three doses]), and their neutralizing capacity was weak. The overall effectiveness of maternal vaccination in preventing infant infection was 27.0%, and three doses had higher effectiveness than two doses (64.3% vs. 19.6%). Multivariate analysises showed that in vaccination group women receiving three doses or in infection group women with longer interval between infection and delivery had a higher antibody transfer rate and neonatal IgG antibody titer. More than half of women vaccinated before or during early pregnancy can achieve effective antibody transfer to newborns. However, the neonatal IgG antibody titer is low and has a weak neutralizing capacity, providing limited protection to infants.

Adeno-associated virus serotype 9 antibody seroprevalence for patients in the United States with spinal muscular atrophy

Onasemnogene abeparvovec is a recombinant adeno-associated virus serotype 9 (AAV9) vector-based gene therapy for spinal muscular atrophy (SMA). Patients with elevated titers of anti-AAV9 antibodies (AAV9-Ab) should not receive onasemnogene abeparvovec because of potential safety and efficacy implications. We conducted a retrospective study to describe the seroprevalence of anti-AAV9 binding antibodies for pediatric patients with SMA in the United States. At initial testing, 13.0% (115 of 882) of patients (mean [SD] age, 26.29 [33.66] weeks) had elevated AAV9-Ab titers. The prevalence of elevated titers decreased as age increased, with 18.2% (92 of 507) of patients ≤3months old but only 1.1% (1 of 92) of patients≥21months old having elevated titers. This suggests transplacental maternal transfer of antibodies. No patterns of geographic variations in AAV9-Ab prevalence were confirmed. Elevated AAV9-Ab titers in children <6weeks old decreased in all circumstances. Lower magnitudes of elevated titers declined more rapidly than greater magnitudes. Retesting was completed at the discretion of the treating clinician, so age at testing and time between tests varied. AAV9-Ab retesting should be considered when patients have elevated titers, and elevations at a young age are not a deterrent to eventual onasemnogene abeparvovec administration. Early disease-modifying treatment for SMA leads to optimal outcomes.

Vertical transfer of maternal pathogen-specific antibodies in successive pregnancies and infection risk in infancy

Vertical transfer of maternal pathogen-specific antibodies in successive pregnancies and infection risk in infancy

Developmental and reproductive safety of Advax-CpG55.2™ adjuvanted COVID-19 and influenza vaccines in mice

SpikoGen® is a recombinant spike protein vaccine against COVID-19 that obtained marketing authorization in the Middle East on October 6th, 2021, becoming the first adjuvanted protein-based COVID-19 vaccine of its type to achieve approval. SpikoGen® vaccine utilizes a unique adjuvant Advax-CpG55.2, which comprises delta inulin and CpG55.2 oligonucleotide, a synthetic human toll-like receptor (TLR)-9 agonist. As part of a safety assessment, developmental and reproductive toxicity (DART) studies were undertaken in mice of Advax-CpG55.2 adjuvanted formulations including SpikoGen®, a H7 hemagglutinin influenza vaccine (rH7HA), the bivalent combination of SpikoGen® and rH7HA, and a next-generation quadrivalent spike protein vaccine. In the first study, vaccines were administered intramuscularly to pregnant dams on gestation days (GD) 6.5 and 12.5, and in the second two doses were given in the pre-mating period with a further two doses during gestation. The doses used in the pregnant mice were 250–1000 times the usual human doses on a weight for weight basis. Strong serum antibody responses with neutralizing activity against the relevant virus were seen in the immunized dams and also at the time of weaning in the sera of their pups, consistent with robust maternal antibody transfer. No adverse effects of any of the vaccine formulations were observed in the immunized dams or their pups. Notably, there were no adverse effects of any of the Advax-CpG55.2 adjuvanted vaccines on female mating performance, fertility, ovarian or uterine parameters, embryo-fetal or postnatal survival, fetal growth, or neurofunctional development. No evidence of antigen interference was observed when SpikoGen® vaccine was mixed and co-administered with influenza hemagglutinin vaccine to pregnant dams. Together with the strong safety profile of SpikoGen® vaccine seen in adults and children in human trials, this DART study data supports the safety of Advax-CpG55.2 adjuvanted COVID-19 and influenza vaccine in women of childbearing potential including during pregnancy.

Serologic evolution and follow-up to IgG antibodies of infants born to mothers with gestational COVID

BackgroundIt is known that SARS-CoV-2 antibodies from pregnant women with SARS-CoV-2 infection during pregnancy cross the placenta but the duration and the protective effect of these antibodies in infants is scarce.MethodsThis prospective study included mothers with SARS-COV-2 infection during pregnancy and their infants from April 2020 to March 2021. IgG antibodies to SARS-CoV-2 spike protein were performed on women and infants at birth and at two and six months during follow-up. Anthropometrical measures and physical and neurological examinations and a clinical history of symptoms and COVID-19 diagnosis were collected. Simple linear regression was performed to compare categorical and continuous variables. To compare the mother’s and infant’s antibody titers evolution, a mixed linear regression model was used. A predictive model of newborn antibody titers at birth has been established by means of simple stepwise linear regression.Results51 mother-infant couples were included. 45 (90%) of the mothers and 44 (86.3%) of the newborns had a positive serology al birth. These antibodies were progressively decreasing and were positive in 34 (66.7%) and 7 (13.7%) of infants at 2 and 6 months, respectively. IgG titers of newborns at birth were related to mothers’ titers, with a positive moderate correlation (Pearson’s correlation coefficient: 0.82, p < 0,001). Fetal/maternal antibodies placental transference rate was 1.3 (IQR: 0.7–2.2). The maternal IgG titers at delivery and the type of maternal infection (acute, recent, or past infection) was significantly related with infants’ antibody titers at birth. No other epidemiological or clinical factors were related to antibodies titers. Neurodevelopment, psychomotor development, and growth were normal in 94.2% of infants in the third follow-up visit. No infants had a COVID-19 diagnosis during the follow-up period.ConclusionsTransplacental transfer of maternal antibodies is high in newborns from mothers with recent or past infection at delivery, but these antibodies decrease after the first months of life. Infant’s IgG titers were related to maternal IgG titers at delivery. Further studies are needed to learn about the protective role of maternal antibodies in infants.

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.

Clinical outcomes and antibody transfer in a cohort of infants with in utero or perinatal exposure to SARS-CoV-2 (Coronascope Study).

In this cohort, the majority of infants born to mothers with COVID-19 during pregnancy were healthy infants with a normal cUS, no hearing loss, and normal neurodevelopment in the first year of life. Only half of the infants had a positive serological result during the follow-up. • Hearing loss and neurodevelopmental delay in infants born to mothers with COVID-19 during pregnancy has been suggested, although data is inconsistent. Maternal antibody transfer seems to be high, with a rapid decrease during the first weeks of life. • Most infants born to mothers with COVID-19 during pregnancy had normal hearing screening, cranial ultrasound, and neurodevelopmental status at 12months of life. Antibodies against SARS-CoV-2 were only detected in 50% of the infants at two months of life.