Safety of tetanus,diphtheria, acellular pertussis (Tdap) vaccination during pregnancy

The objective of this study was to evaluate the safety of prenatal tetanus, diphtheria, acellular pertussis (Tdap) vaccination. This cohort study was conducted among pregnant members at Kaiser Permanente Southern California (KPSC). The exposed cohort consisted of women who received Tdap vaccine on or after the 27th week of pregnancy between January 2018 and January 2019. The unexposed cohort consisted of matched women who were pregnant between January 2012 and December 2014 and were not vaccinated with any Tdap vaccine throughout their pregnancy. Maternal and infant characteristics and pre-specified endpoints were collected through automated data and review of the electronic health records. Unadjusted and adjusted relative risks (aRRs) with confidence intervals (CIs) were estimated by Poisson regression. Non-inferiority testing (i.e., to rule out a two-fold increase) was conducted for primary endpoints with adjustment for multiplicity. Superiority testing was conducted without multiplicity adjustment for secondary endpoints. The analysis consisted of 16,606 pairs of Tdap recipients and unexposed pregnant women. For the primary endpoints, the aRR for preeclampsia/eclampsia was 1.38 (98.75% CI:1.21–1.58) and the aRR for intrauterine infection was 1.28 (98.75% CI:1.12–1.47). These increases were consistent with the background increasing trend of these diagnoses among all pregnant women at KPSC since 2011, and the upper limit of the 98.75% CI of both aRRs did not exceed the pre-specified threshold of 2. No increased risks of small for gestational age (aRR = 1.04, 98.75% CI:0.94–1.16) or preterm delivery (aRR = 0.71, 98.75% CI:0.64–0.78) were observed. No evidence of increased risks for secondary endpoints, including poor fetal growth, preterm pre-labor rupture of membranes, stillbirth/fetal death, placental abruption, transfusion during delivery hospitalization, and neonatal death, was observed. Prenatal Tdap vaccination after the 27th week of pregnancy was not associated with increased risks of pre-specified maternal and infant outcomes, supporting the safety of Tdap vaccination during pregnancy.     

Improving influenza and Tdap vaccination during pregnancy: A cluster-randomized trial of a multi-component antenatal vaccine promotion package in late influenza season

BackgroundEvidence-based interventions to improve influenza vaccine coverage among pregnant women are needed, particularly among those who remain unvaccinated late into the influenza season. Improving rates of antenatal tetanus, diphtheria and acellular pertussis (Tdap) vaccination is also needed.PurposeTo test the effectiveness of a practice-, provider-, and patient-focused influenza and Tdap vaccine promotion package on improving antenatal influenza and Tdap vaccination in the obstetric setting.MethodsA cluster-randomized trial among 11 obstetric practices in Georgia was conducted in 2012–2013. Intervention practices adopted the intervention package that included identification of a vaccine champion, provider-to-patient talking points, educational brochures, posters, lapel buttons, and iPads loaded with a patient-centered tutorial. Participants were recruited from December 2012–April 2013 and included 325 unvaccinated pregnant women in Georgia. Random effects regression models were used to evaluate primary and secondary outcomes.ResultsData on antenatal influenza and Tdap vaccine receipt were obtained for 300 (92.3%) and 291 (89.5%) women, respectively. Although antenatal influenza and Tdap vaccination rates were higher in the intervention group than the control group, improvements were not significant (For influenza: risk difference (RD) = 3.6%, 95% confidence interval (CI): −4.0%, 11.2%; for Tdap: RD = 1.3%, 95% CI: −10.7%, 13.2%). While the majority of intervention package components were positively associated with antenatal vaccine receipt, a provider's recommendation was the factor most strongly associated with actual receipt, regardless of study group or vaccine.ConclusionsThe intervention package did not significantly improve antenatal influenza or Tdap vaccine coverage. More research is needed to determine what motivates women remaining unvaccinated against influenza late into the influenza season to get vaccinated. Future research should quantify the extent to which clinical interventions can bolster a provider's recommendation for vaccination. This study is registered with clinicaltrials.gov, study ID NCT01761799.     

Mother-infant vaccination with pneumococcal polysaccharide vaccine: persistence of maternal antibodies and responses of infants to vaccination

Protection against pneumococcal infection early in life is needed. This could be achieved by maternal vaccination or by starting infant vaccinations as early as possible. In an open controlled study, pregnant women received both 23-valent pneumococcal polysaccharide vaccine (PPV), Haemophilus influenzae type b conjugate vaccine and tetanus toxoid or tetanus toxoid alone. Infants received PPV at 7 or 17 weeks and the second dose at 3 years of age. Antibodies to six pneumococcal serotypes were measured with the non-22F and 22F enzyme immunoassays (EIA). Elevated antibody concentrations after maternal vaccination persisted in infants until 4 months of age. Infants responded to serotypes 1 and 5, but not to serotypes 6B, 14, 18C and 19F. High maternal antibody concentrations at early age reduced the responses, but not the antibody concentrations, of infants to PPV. The percentages of infants with concentrations >0.35 μg/ml and >1 μg/ml were high at birth, but decreased by age during the first 10 months of life. Revaccination with PPV at 3 years of age induced a good immune response.     

Kinetics of maternal pertussis-specific antibodies in infants of mothers vaccinated with tetanus,diphtheria and acellular pertussis (Tdap) during pregnancy

BackgroundKinetics of Tdap-induced maternally-derived antibodies in infants are poorly understood. Pre-Tdap era data suggest that maternal pertussis antibodies in infants have a half-life of approximately 5–6 weeks.Methods34 mother-infant pairs had blood collected before maternal Tdap vaccination, 4 weeks later, at delivery (maternal and cord), and at infant ages 3 and 6 weeks from June 2014-March 2015. Immunoglobulin G (IgG) to pertussis toxin (PT), filamentous hemagglutinin (FHA), fimbrial proteins (FIM) and pertactin (PRN) was quantified by multiplex luminex assay (IU/ml). Geometric mean concentrations (GMCs) with 95% confidence intervals (C.I.) and half-life of pertussis antibodies were calculated.ResultsTdap was administered to 34 women (mean age 31.1 years) at mean gestation 30.7 weeks (28–32.7). Mean neonatal gestation was 39.1 weeks (36–41.1) and mean birthweight was 3379 g (2580–4584). Four weeks post-Tdap vaccination, maternal pertussis-specific IgG GMCs increased ≥4-fold in 59%, 41%, 29% and 44% of women for PT, FHA, FIM and PRN, respectively, and then waned. The transplacental transport ratio of pertussis antibodies was 1.35 for PT, 1.41 for FHA, 1.31 for FIM and 1.36 for PRN. Between birth and age 6 weeks, infant serum GMC for PT-specific IgG decreased from 55.1 IU/mL (38.6–78.6) to 21.1 IU/ml (14.7–30.2), and the proportion of infants with PT levels ≥10 IU/ml fell from 97% to 67%. Half-life of pertussis-specific IgG in infants in days was 29.4 (95% CI 27.3–31.7) for PT, 29.8 (95% CI 27.7–32.2) for FHA, 31.2 (95% CI 28.9–33.7) for PRN, and 35.8 (95% CI 30.1–44.3) for FIM.ConclusionThe half-life of pertussis-specific antibodies in infants induced by maternal Tdap vaccination (29–36 days) is shorter than previously reported. Understanding how the durability of passively-acquired antibodies impacts infant susceptibility to pertussis and response to primary vaccination is critical to refine prevention strategies.     

Tdap vaccination during pregnancy interrupts a twenty-year increase in the incidence of pertussis

Pertussis incidence in developed countries, including Israel, has increased over the past two decades despite the addition of two booster doses in children. However, as pertussis is characterized by a multi-annual periodicity, and since clinical diagnosis can miss cases, determining disease trends at the population level is challenging. To bridge this gap, we developed a simple statistical model to capture the temporal patterns of pertussis incidence in Israel. Our model was calibrated and tested using laboratory-confirmed cases of pertussis for the Israeli population between 1998 and 2019. The model identifies a clear four-year periodicity of pertussis incidence over the past two decades that is identical to the one observed in the pre-vaccine era. Accounting for this periodicity, the model shows a 325% increase in pertussis incidence from 2002 to 2014. These multi-year trends were interrupted shortly after the introduction of routine immunization of Tdap vaccine in pregnancy in 2015, after which we found a 59.7% (95% CI: 57.7–61.6%) decline in pertussis incidence and a 49.5% (36.0–61.6%) decline in hospitalizations compared to the model’s projection. While this sharp decline cannot be fully attributed to the newly introduced vaccination policy, sharper reductions of 71.2% (65.6–76.1%) in incidence and 58.4% (39.6–72.7%) in hospitalizations, have been observed in infants of age two months and below - young infants that have yet to become vaccinated and are more likely to be protected by maternal vaccination. Our work suggests that Tdap vaccination during pregnancy is a promising policy for controlling pertussis. Furthermore, due to the stable periodicity of pertussis, public health decision-makers should invest continuous efforts in the implementation of this strategy with additional reinforcement in expected peak years.     

Acquisition of specific antibodies and their influence on cell-mediated immune response in neonatal cord blood after maternal pertussis vaccination during pregnancy

Maternal immunization with pertussis acellular vaccine (Tdap) is an intervention that provides protection to newborns. However, it has been reported that high maternal antibody levels may adversely affect the immune response of infants after active immunization. In this study, we evaluated neonatal passive acquisition of pertussis-specific antibodies and their influence on the neonatal cell-mediated immune response.Pregnant women were either vaccinated with Tdap vaccine (case group, n?=?66) or received no vaccine (control group, n?=?101). Whole-cell Bordetella pertussis (Bp), pertussis toxin (PT), filamentous hemagglutinin (FHA) and pertactin (PRN)-specific serum IgG were quantified in paired maternal-cord sera, and Bp- and PT-specific IgA were evaluated in colostrum by ELISA. Ex vivo neonatal blood lymphocyte responsiveness after Bp stimulation was assessed in case (n?=?17) and control (n?=?15) groups using flow cytometry to detect proliferation, cytokine production and activation phenotype of lymphocytes in the context of high specific IgG acquired after maternal vaccination.Anti-Bp, PT, FHA and PRN IgG concentrations in maternal and cord sera from case group were higher than those in control group with positive correlation indexes in both groups for all pertussis antigens. The control group presented higher placental transfer ratios of specific antibodies and, in the case group, vaccination between 26 and 31 gestation weeks was associated with the best placental transfer ratios. Specific IgA concentrations in colostrum were not affected by vaccine status. Whole blood assays revealed that newborns responded to Bp stimulation with higher expression of CD40L, CD69 and CD4⁺ T cell proliferation compared to unstimulated cells, and a lower Th1 response, while a preserved Th2 response compared to adults, but there were no differences between the neonatal groups for any of the studied parameters.Our results indicate that higher pertussis-specific IgG levels in newborn sera after maternal vaccination do not affect the neonatal ex vivo cell-mediated immune response.     

Safety of tetanus,diphtheria, and acellular pertussis vaccination among pregnant active duty U.S. military women

BackgroundThe tetanus, diphtheria, and acellular pertussis (Tdap) vaccine was approved for U.S. adults in 2005 and recommended for administration in every pregnancy in 2012, with optimal timing between 27 and 36 weeks’ gestation. In the military, however, a current Tdap vaccination status is compulsory for service, and active duty women may be inadvertently exposed in early pregnancy. Safety data in this population are limited.ObjectivesTo assess safety of inadvertent (0–13 weeks’ gestation) and recommended (27–36 weeks’ gestation) exposure to the Tdap vaccine in pregnancy.MethodsPregnancies and live births from Department of Defense Birth and Infant Health Research program data were linked with military personnel immunization records to determine pregnancy Tdap vaccine exposure among active duty women, 2006–2014. Multivariable Cox and generalized linear regression models estimated associations between Tdap vaccine exposure and adverse pregnancy or infant outcomes.ResultsOf 145,883 pregnancies, 1272 were exposed to the Tdap vaccine in the first trimester and 9438 between 27 and 36 weeks’ gestation. Neither inadvertent nor recommended vaccine exposure were associated with spontaneous abortion, preeclampsia, or preterm labor. Among 117,724 live born infants, 984 were exposed to the Tdap vaccine in the first trimester and 9352 between 27 and 36 weeks’ gestation. First trimester exposure was not associated with birth defects, growth problems in utero, growth problems in infancy, preterm birth, or low birth weight. Tdap vaccine exposure between 27 and 36 weeks’ gestation was not associated with any adverse infant outcome.ConclusionsAmong a population of active duty women in the U.S. military who received the Tdap vaccine during pregnancy, we detected no increased risks for adverse maternal, fetal, or infant outcomes. Our findings corroborate existing literature on the safety of exposure to the Tdap vaccine in pregnancy.     

Evaluation of two vaccine education interventions to improve pertussis vaccination among pregnant African American women: A randomized controlled trial

BackgroundVaccination coverage with tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine in pregnancy or immediately postpartum has been low. Limited data exist on rigorously evaluated interventions to increase maternal vaccination, including Tdap. Tailored messaging based on the Elaboration Likelihood Model (ELM) framework has been successful in improving uptake of some public health interventions. We evaluated the effect of two ELM-based vaccine educational interventions on Tdap vaccination among pregnant African American women, a group of women who tend to have lower vaccine uptake compared with other groups.MethodsWe conducted a prospective randomized controlled trial to pilot test two interventions – an affective messaging video and a cognitive messaging iBook – among pregnant African American women recruited during routine prenatal care visits. We measured Tdap vaccination during the perinatal period (during pregnancy and immediately postpartum), reasons for non-vaccination, and intention to receive Tdap in the next pregnancy.ResultsAmong the enrolled women (n = 106), 90% completed follow-up. Tdap vaccination in the perinatal period was 18% in the control group; 50% in the iBook group (Risk Ratio [vs. control group]: 2.83; 95% CI, 1.26–6.37), and 29% in the video group (RR: 1.65; 95% CI, 0.66–4.09). From baseline to follow-up, women’s reported intention to receive Tdap during the next pregnancy improved in all three groups. Among unvaccinated women, the most common reason reported for non-vaccination was lack of a recommendation for Tdap by the woman’s physician.ConclusionsEducation interventions that provide targeted information for pregnant women in an interactive manner may be useful to improve Tdap vaccination during the perinatal period. However, larger studies including multiple racial and ethnic groups are needed to evaluate robustness of our findings.Trial Registration: clinicaltrials.gov Identifier: NCT01740310.     

Universal tetanus,diphtheria, acellular pertussis (Tdap) vaccination of adults: What the Canadian public knows and wants to know

Tetanus, diphtheria, and acellular pertussis vaccine (Tdap) is recommended for all adults in Canada but uptake is low. This study measured the knowledge, attitudes, beliefs, and behaviors of Canadian adults to identify potential barriers and facilitators to Tdap uptake. A survey was undertaken on a geographically representative sample of Canadian adults (n = 4023) and 8 focus groups (62 participants) were conducted nationwide. The survey revealed that knowledge about pertussis and Tdap was low (38.3% correct answers). Only 36.0% of respondents reported being aware that all adults were recommended to receive Tdap and only 10.7% reported being immunized; 36.7% did not know whether they had received Tdap. Respondents who were aware of the immunization recommendations were twice as likely to be immunized (16.6% vs. 8.3%; p < 0.001). Only 9.3% believed that their health care provider thought that Tdap was important for adults. The focus group data supported the survey results. Participants wanted information about pertussis and Tdap communicated through multiple modalities, but a recommendation by their family physician was most important to their decision to be immunized or not. This study demonstrates that current recommendations for universal adult vaccination with Tdap are not reaching the general public in Canada and an alternative strategy will be required to improve Tdap vaccine uptake.     

Infant antibody levels following 10-valent pneumococcal-protein D conjugate and DTaP-Hib vaccinations in the first year of life after maternal Tdap vaccination: An open-label,parallel, randomised controlled trial

BackgroundMaternal antibody levels after Tdap vaccination during pregnancy may affect infant primary antibody responses to pertussis, Tetanus toxoid (TT), Diphtheria toxoid (DT) vaccinations and pneumococcal vaccines with diphtheria toxin mutants like CRM197 as carrier protein.MethodsMothers were recruited in an open label randomised parallel controlled trial in 2014–2016 through midwifes. They received Tdap [Boostrix] at 30–32 weeks of pregnancy (n = 58) or within 48 h after delivery (n = 60). Infants received DTaP-IPV-Hib-HepB [Infanrix Hexa] and 10-valent protein D conjugated pneumococcal conjugate vaccine (PHiD-CV10 [Synflorix]) at age 3, 5 and 11 months. We now report on infant specific IgG levels towards DT, TT, Haemophilus influenzae type b polyribosylribitol phosphate (Hib PRP) and PHiD-CV10 before and after primary- and booster vaccination as secondary study endpoints; pertussis antibodies were the primary endpoint of the study. This trial is registered in clinicaltrialsregister.eu (EudraCT 2012–004006-9) and trialregister.nl (NTR number NTR4314).FindingsPost primary vaccinations, antibody levels to DT, but not TT, were significantly lower after Tdap vaccination during pregnancy compared to controls (GMC ratio 0.4, 95% CI 0.3–0.6 and 0.9, 95% CI 0.6–1.2, respectively). Antibodies to serotype 19F were significantly lower in the maternal Tdap group, whereas there were no differences in antibody levels to Hib PRP and the other 9 pneumococcal serotypes. Post booster vaccinations, no significant differences were observed, except for DT.InterpretationMaternal Tdap vaccination results in significant interference with infants responses not only to DT but also to conjugated pneumococcal vaccines containing DT mutants as carrier proteins. These interactions after maternal Tdap vaccination need to be taken into account when designing infants’ national immunization schedules and choice of vaccines.FundingThe Dutch Ministry of Health, Welfare and Sport.     

A Phase 2 randomized,observer-blind,placebo-controlled,dose-ranging trial of aluminum-adjuvanted respiratory syncytial virus F particle vaccine formulations in healthy women of childbearing age

ObjectiveRespiratory syncytial virus (RSV) causes significant morbidity and mortality in infants. We are developing an RSV fusion (F) protein nanoparticle vaccine for immunization of third trimester pregnant women to passively protect infants through transfer of RSV-specific maternal antibodies. The present trial was performed to assess the immunogenicity and safety of several formulations of RSV F vaccine in 1-dose or 2-dose schedules.MethodsPlacebo, or vaccine with 60 μg or 120 μg RSV F protein and 0.2, 0.4, or 0.8 mg aluminum, were administered intramuscularly on Days 0 and 28 to healthy women 18–35 years old. Immunogenicity was assessed from Days 0 through 91 based on anti-F IgG and palivizumab-competitive antibody (PCA) by ELISA, and RSV A and B neutralizing antibodies by microneutralization (MN) assay. Solicited adverse events were collected through Day 7 and unsolicited adverse events through Day 91.ResultsAll formulations were well-tolerated, with no treatment-related serious adverse events. Anti-F IgG and PCA responses were correlated and increased after both doses, while MN increased significantly only after the first dose, then plateaued. The timeliest and most robust antibody responses followed one dose of 120 μg RSV F protein and 0.4 mg aluminum, but persistence through 91 days was modestly (∼25%) superior following two doses of 60 μg RSV F protein and 0.8 mg aluminum. Western blot analysis showed RSV infections in active vaccinees were reduced by 52% overall (p = 0.009 overall) over the Day 0 through 90 period.ConclusionsRSV F nanoparticle vaccine formulations were well tolerated and immunogenic. The optimal combination of convenience and rapid response for immunization in the third trimester occurred with 120 μg RSV F and 0.4 mg aluminum, which achieved peak immune responses in 14 days and sufficient persistence through 91 days to allow for passive transfer of IgG antibodies to the fetus. NCT01960686.     

The effect of maternal antibodies on the cellular immune response after infant vaccination: A review

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.     

Declining responsiveness to influenza vaccination with progression of human pregnancy

BackgroundInfluenza immunization is universally recommended during pregnancy to protect mothers and their offspring. However, pregnancy-induced shifts in vaccine responsiveness remain poorly defined.MethodsQuantitative and qualitative shifts in the serological response to influenza vaccination were evaluated in healthy women throughout the course of pregnancy. Serum was obtained before and after vaccination among 71 pregnant and 67 non-pregnant women during the 2011–12 and 2012–13 influenza seasons. Serum hemagglutination inhibition (HAI) assay was used to investigate anti-influenza antibody responses by comparing pre-vaccine and post-vaccine geometric mean titers (GMTs) between groups for each antigen. IgG1, IgG2, IgG3, and IgG4 anti-influenza titers were also evaluated by enzyme-linked immunosorbent assay (ELISA). Pregnancy induced shifts in HAI titers and levels of each anti-influenza antibody isotype were evaluated using linear regression models.ResultsPost-vaccine GMTs at day 28 were significantly reduced for women vaccinated during pregnancy for A/California (H1N1) in 2011 (p = 0.027), A/Perth (H3N2) in 2011 (p = 0.037), and B/Wisconsin in 2012 (p = 0.039). Vaccine responses progressively declined with the initiation of vaccination later in pregnancy. Anti-H1N1 IgG1, IgG2, and IgG3 titers were reduced in pregnant women compared to non-pregnant controls, and these titers declined with pregnancy progression. The most striking differences were found for anti-H1N1 IgG1, where titers decreased by approximately 7% each week throughout pregnancy.ConclusionsHAI responses elicited by immunization were significantly reduced during pregnancy for three different influenza vaccine antigens. Anti-H1N1 IgG1 was significantly lower in pregnant women and decreased throughout the course of pregnancy. Waning serological responsiveness to influenza vaccination with the progression of human pregnancy has important translational implications for when immunization should be optimally administered during pregnancy.     

Maternal pneumococcal capsular IgG antibodies and transplacental transfer are low in South Asian HIV-infected mother-infant pairs

Background

Our understanding of the mother-to-child transfer of serotype-specific pneumococcal antibodies is limited in non-immunized, HIV-positive women.

Methods

We compared geometric mean antibody concentrations (GMCs), geometric mean transplacental cord:maternal ratios (GMRs) and proportions of samples with protective antibody concentration (≥0.35 μg/ml) to serotypes 1, 4, 5, 6B, 9V, 14, 18C, 19F, 23F between 74 HIV-infected and 98 HIV-uninfected mother-infant pairs who had not received pneumococcal immunization in South Asia. Multivariable analysis was performed to assess the influence of HIV on protective antibody concentrations.

Results

HIV-infected mothers and their infants exhibited lower GMCs and GMRs than their uninfected counterparts. This was significant for all serotypes except maternal GMC to serotype 1 and GMR for serotype 6B. In multivariate analysis, HIV was significantly associated with reduced odds of having protective pneumococcal IgG levels; 56–73% reduction for 3 maternal serotypes (4, 5, 23F) and 62–90% reduction for all cord samples except serotype 6B.

Conclusions

Maternal HIV infection is associated with lower levels of maternal pneumococcal antibodies and disproportionately lower cord antibodies, relative to maternal antibodies, suggesting that HIV infection compromises transplacental transfer. Reassessment of maternal and/or infant pneumococcal immunization strategies is needed in HIV-infected women and their infants.     

母婴血清IgG及亚类含量与胎盘转运率

目的探讨新生儿和妊娠母亲血清IgG及其亚类含量与胎盘转运率的关系.方法采用速率散射比浊法,同时测定43组配对新生儿、脐血、母亲和45例对照组成人血清中IgG和IgG1、IgG2、IgG3、IgG4(IgG1～4)含量.结果血清IgG含量新生儿＜母亲、脐血和对照组(P＜0.05);IgG2含量新生儿和脐血＜对照组＜母亲(P＜0.05);IgG1、IgG3和IgG4含量在新生 儿、脐血、母亲和对照组间差异无显著性(P＞0.05);母婴间血清IgG、IgG1～4的转运率IgG3＞IgG1＞IgG＞IgG4＞IgG2(P＜0.01).结论新生儿血清IgG含量低于母亲,与其IgG2含量低有关;母婴IgG及其亚类的胎盘转运率的差异是影响新生儿血清IgG、IgG1～4含量的重要原因之一.     

Maternal Tdap vaccination and risk of infant morbidity

IntroductionAn increased risk of diagnosed chorioamnionitis in women vaccinated with Tdap during pregnancy was previously detected at two Vaccine Safety Datalink (VSD) sites. The clinical significance of this finding related to infant outcomes remains uncertain.MethodsRetrospective cohort study of singleton live births born to women who were continuously insured from 6 months prior to their last menstrual period through 6 weeks postpartum, with ≥1 outpatient visit during pregnancy from January 1, 2010 to November 15, 2013 at seven integrated United States health care systems part of the VSD. We re-evaluated the association between maternal Tdap and chorioamnionitis and evaluated whether specific infant morbidities differ among infants born to mothers who did and did not receive Tdap during pregnancy. We focused on 2 Tdap exposure windows: the recommended 27–36 weeks gestation or anytime during pregnancy. We identified inpatient diagnostic codes for transient tachypnea of the newborn (TTN), neonatal sepsis, neonatal pneumonia, respiratory distress syndrome (RDS), and newborn convulsions associated with an infant's first hospitalization. A generalized linear model with Poisson distribution and log-link was used to estimate propensity score adjusted rate ratios (ARR) with 95% confidence intervals (CI).ResultsThe analyses included 197,564 pregnancies. Chorioamnionitis was recorded in 6.4% of women who received Tdap vaccination any time during pregnancy and 5.2% of women who did not (ARR [95% CI]: 1.23 [1.17, 1.28]). Compared with unvaccinated women, there were no significant increased risks (ARR [95% CI]) for TTN (1.04 [0.98, 1.11]), neonatal sepsis (1.06 [0.91, 1.23]), neonatal pneumonia (0.94 [0.72, 1.22]), RDS (0.91 [0.66, 1.26]), or newborn convulsions (1.16 [0.87, 1.53]) in infants born to Tdap-vaccinated women.Conclusions and RelevanceDespite an observed association between maternal Tdap vaccination and maternal chorioamnionitis, we did not find increased risk for clinically significant infant outcomes associated with maternal chorioamnionitis.     

Prevalence of IgM and IgG antibodies to Toxoplasma gondii in blood donors in the Czech Republic

Blood donors (n=663) from the Nový Jiín district, Czech Republic, were examined for the presence of antibodies to Toxoplasma gondii. The indirect fluorescent antibody test was used to simultaneously detect IgM and IgG antibodies. Titres 20 were considered positive. The seroprevalence of IgM and IgG antibodies was 2.4% and 32.1%, respectively. Periods, for how long the blood donors were infected, are discussed.     

Modeling maternal fetal RSV F vaccine induced antibody transfer in guinea pigs

BackgroundProtection of newborns and young infants against RSV disease via maternal immunization mediated by transplacental transfer of antibodies is under evaluation in third-trimester pregnant women with the RSV recombinant F nanoparticle vaccine (RSV F vaccine). Since the hemichorial placental architecture in guinea pigs and humans is similar, the guinea pig model was employed to assess RSV F vaccine immunogenicity in pregnant sows and to compare RSV-specific maternal antibody levels in their pups.MethodsThirty (30) presumptive pregnant guinea pigs were immunized on gestational day 25 and 46 with placebo (PBS), 30 μg RSV F, or 30 μg RSV F + 400 μg aluminum phosphate. Sera at delivery/birth (sows/pups) and 15 and 30 days post-partum (pups) were analyzed for the presence of anti-F IgG, palivizumab-competitive antibody (PCA) and RSV/A microneutralization (MN).ResultsThe rates of pregnancy and stillbirth were similar between controls and vaccinees. The vaccine induced high levels of anti-F IgG, PCA and MN in sows, with the highest levels observed in adjuvanted vaccinees. Placental transfer to pups was proportional to the maternal antibody levels, with concentration effects observed for all immune measures.ConclusionsThe RSV F vaccine was safe and immunogenic in pregnant guinea pigs and supported robust transplacental antibody transfer to their pups. Relative concentration of antibodies in the pups was observed even in the presence of high levels of maternal antibody. Guinea pigs may be an important safety and immunogenicity model for preclinical assessment of candidate vaccines for maternal immunization.     

Safety and immunogenicity of three seasonal inactivated influenza vaccines among pregnant women and antibody persistence in their infants

ObjectiveInactivated influenza virus vaccines (IIVs) are recommended for all pregnant women in the United States. We conducted a prospective, randomized, double blind study of three licensed seasonal trivalent IIVs (IIV3s) to assess their safety and immunogenicity in pregnant women and determine the level and persistence of passively transferred maternal antibody in infants.Study design139 pregnant women ages 18–39 years and 14–33 weeks’ gestation, and 44 non-pregnant women, were randomized 1:1:1 to receive a single intramuscular dose of one of three licensed IIV3s (Agriflu®, Fluzone®, or Fluarix®) prior to the 2010–2011 influenza season. Reactogenicity, adverse events (AEs) and pregnancy outcomes were documented. Serum samples for hemagglutination inhibition (HAI) and neutralization antibody assays were collected prior to and 28 and 180 days after immunization. Maternal sera and cord blood were collected at the time of delivery and sera were obtained from 44 infants at 6 weeks of age.ResultsPregnant and non-pregnant women experienced similar frequency of injection site (92% and 86%, respectively) and systemic (95% and 87%, respectively) reactions, the majority of which were mild. There were no vaccine-associated maternal or infant serious AEs. Antibody responses to the three vaccine antigens were not different between pregnant and non-pregnant women. The ratios of cord blood (infant) to maternal HAI antibody titers at delivery ranged between 1.1 and 1.7 for each of the vaccine antigens. Influenza antibody concentrations in infants were 70–40% of the birth titer by 6 weeks of age.ConclusionsThe three IIV3s were well tolerated in pregnant women. Antibody responses were comparable in pregnant and non-pregnant women, and after second or third trimester vaccination. Transplacental transfer of maternal antibodies to the infant was efficient. However, antibody titers decline rapidly in the first 6 weeks of life.     

Infant immunity against viral infections is advanced by the placenta-dependent vertical transfer of maternal antibodies

Neonatal passive immunity, derived from transplacental transfer of IgG antibodies from mother to fetus during pregnancy, can mitigate the risk for severe infections in the early postnatal period. Understanding the placenta as the gateway organ in this process, we aimed to evaluate the influence of specific factors modulating the transplacental IgG transfer rate (TPTR) in 141 mother/neonate pairs. We further evaluated the potential health advantage elicited by maternal IgG with regard to respiratory tract infections during infancy and early childhood. Data and biological samples collected within the prospective longitudinal pregnancy cohort study PRINCE (Prenatal Identification of Children’s Health) were used for these analyses. We tested IgG antibody levels against seven pathogens (measles, mumps, rubella, tetanus, diphtheria, pertussis and influenza A) by ELISA and detected seropositivity in 72.6–100% of pregnant women and in 76.3–100% of their neonates, respectively. Cord blood IgG levels reached 137–160% of levels detected in maternal blood. Strikingly, assessment of TPTR for all seven antigens highlighted that TPTR strongly depends on individual placental function. Subsequent in-depth analysis of anti-influenza A IgG revealed a link between cord blood levels and uterine perfusion, measured by uterine artery pulsatility index. Moreover, higher cord blood anti-influenza A IgG levels were associated with a significantly reduced risk for respiratory tract infections during the first six months of life, indicating a high degree of cross-reactivity and possible pathogen-agnostic effects of anti-influenza A antibodies. Taken together, our data suggest that early life immunity is modulated by maternal IgG levels and individual placental features such as perfusion. Vaccination of pregnant women, i.e. against influenza, can increase neonatal antibody levels and hereby protect against early life respiratory infections. Consequently, specific guidelines should evolve in order to safeguard neonates born from pregnancies with poorer placental capacity for vertical transfer of protective antibodies.