•Maternal Abs may inhibit the infant’s humoral immune response to several antigens.•Infant CMI responses in presence of maternal Abs are less extensively studied.•Maternal Abs allow priming of CMI ...responses after infant vaccination.•Exact mechanisms and influences of maternal Abs on T cells remain unknown.
During the last few decades, maternal immunization as a strategy to protect young infants from infectious diseases has been increasingly recommended, yet some issues have emerged. Studies have shown that for several vaccines, such as live attenuated, toxoid and conjugated vaccines, high maternal antibody titers inhibit the infant’s humoral immune response after infant vaccination. However, it is not clear whether this decreased antibody titer has any clinical impact on the infant’s protection, as the cellular immune responses are often equally important in providing disease protection and may therefore compensate for diminished antibody levels. Reports describing the effect of maternal antibodies on the cellular immune response after infant vaccination are scarce, probably because such studies are expensive, labor intensive and utilize poorly standardized laboratory techniques. Therefore, this review aims to shed light on what is currently known about the cellular immune responses after infant vaccination in the presence of high (maternal) antibody titers both in animal and human studies. Overall, the findings suggest that maternally derived antibodies do not interfere with the cellular immune responses after infant vaccination. However, more research in humans is clearly needed, as most data originate from animal studies.
Exploring factors that affect immune responses to immunizations in infants born to women immunized with tetanus-diphtheria-acellular-pertussis (Tdap) in pregnancy compared with unimmunized women is ...important in designing immunization programs.
Individual-participant data meta-analysis of 8 studies reporting post-immunization immunoglobulin G (IgG) levels to vaccine antigens in infants born to either women immunized with Tdap in pregnancy or unimmunized women, using mixed-effects models.
In infants of Tdap-immunized women, two-fold higher levels of anti-pertussis toxin (PT) and anti-diphtheria-toxoid (DT) IgG pre-primary immunization were associated with 9% and 10% lower post-primary immunization levels, (geometric mean ratio GMR, PT: 0.91; 95% CI, 0.88–0.95,n = 494, DT: 0.9; 0.87–0.93,n = 519). Timing of immunization in pregnancy did not affect post-primary immunization anti-Bordetella pertussis, anti-tetanus-toxoid (TT) and anti-DT IgG levels. Spacing of infant immunization did not affect post-primary immunization anti-B. pertussis and anti-DT levels. In infants of Tdap-immunized women, two-fold higher levels of anti-PT and anti-filamentous haemagglutinin (FHA) IgG pre-primary immunization were associated with lower post-booster immunization levels, (GMR, PT: 0.91; 0.85–0.97,n = 224, FHA: 0.92; 0.85–0.99,n = 232). Timing of immunization in pregnancy did not affect post-booster immunization anti-Bordetella pertussis, anti-tetanus-toxoid (TT) and anti-DT IgG levels. Spacing of infant immunization did not affect post-booster immunization anti-PT, anti-pertactin (PRN), anti-TT and anti-DT IgG levels.
In infants of unimmunized women, two-fold higher IgG levels of some vaccine antigens pre-primary immunization were associated with 8–17% lower post-primary immunization levels (GMR, PT 0.92, 95% CI:0.88–0.97, n = 373; FHA:0.88, 95% CI:0.85–0.92,n = 378; PRN:0.84, 95% CI:0.81–0.88, n = 367; TT:0.88, 95% CI:0.83–0.93, n = 241; DT: 0.83, 95% CI:0.79–0.87,n = 278). Two-fold higher levels of anti-FHA IgG pre-primary immunization were associated with 8% lower post-booster immunization levels (GMR, 0.92; 95% CI: 0.86–0.99,n = 138).
Increased IgG levels pre-primary immunization is associated with reduced post-primary and post-booster immunization levels for some antigens in infants of women immunized or unimmunized in pregnancy, but their clinical significance is uncertain.
Background. Maternal antibodies to pertussis can hamper infant immune responses to pertussis vaccines. The effect a maternal tetanus, diphtheria, acellular pertussis (Tdap) vaccine booster between 2 ...consecutive pregnancies is investigated. Methods. A prospective study was conducted in Belgium during 2008–2014 on the kinetics of maternal pertussis antibodies in unvaccinated women and their infants (group A; 86 mother-infant pairs) and in siblings born after the women received Tdap vaccine (group B; 58 mother-infant pairs). Levels of antibody to pertussis toxin, antibody to filamentous hemagglutinin, and antibody to pertactin were measured in maternal blood before and after vaccination and at both deliveries, in cord blood from both siblings, and in infants before and after they received a priming series of acellular pertussis containing vaccines. Results. Levels of pertussis antibodies in all group B siblings at birth were significantly higher than those in their siblings at birth, even as the interval since maternal vaccination increased. Blunting of the infant pertussis vaccine response was detected in group B siblings. We estimated the maximum interval between repeat Tdap vaccine doses in adult women that would yield a beneficial effect for the consecutive infant. Conclusions. Prepregnancy Tdap vaccination significantly increases maternal antibody concentrations in consecutive infants. However, similar to the effect of Tdap vaccination during pregnancy, immune responses of later-born infants born to mothers who received a prepregnancy immunization, are blunted.
Enrichment of breast milk (BM) with immunoglobulin (Ig) A and IgG through maternal vaccination could help infants combat targeted pathogens. However, evidence on this effect after preterm delivery is ...lacking. In this study, we investigated the total and anti-pertussis toxin (anti-PT)-specific IgA and IgG production in BM after term and preterm delivery in the presence of maternal Tdap (tetanus, diphtheria, acellular pertussis) vaccination.
Serum and BM samples of lactating women who delivered at term or prematurely and did or did not receive Tdap vaccine (Boostrix, GSK Biologicals) during pregnancy were collected as part of a clinical study (N = 234). Anti-PT IgA/IgG (IBL assay; Meso Scale Discovery assay) and total IgA/IgG (Thermofisher, on BM samples only) immunosorbent assays were performed on all samples collected at 72 hours and 4, 8, and 12 weeks postpartum.
BM after preterm delivery contained anti-PT IgA and IgG geometric mean concentrations (GMCs) comparable to those after term delivery (eg, colostrum anti-PT IgA, 5.39 IU/mL vs 6.69 IU/mL, respectively). Maternal Tdap vaccination induced significantly higher anti-PT IgG GMCs in colostrum of vaccinated compared with unvaccinated women who delivered at term (0.110 IU/mL vs 0.027 IU/mL, P = .009). Anti-PT antibodies persisted up to 12 weeks postpartum.
This study provides evidence that maternal Tdap vaccination induces high Ig levels in BM after both term and preterm delivery and that these antibodies remain abundantly present throughout lactation, possibly offering additional mucosal protection during the most vulnerable period in early life.
NCT02511327.
In Thailand, the hepatitis B (HB) vaccine is administered as a tetravalent vaccine (DTwP-HB) to all infants at 2, 4, and 6 months of age, following an initial vaccination with a monovalent HB vaccine ...at birth. As part of ongoing vaccine evaluation, we aimed to compare the hepatitis B immunogenicity profiles of children who had received either the pentavalent (DTwP-HB-Hib) or the hexavalent (DTaP-HB-Hib-IPV) vaccine.
Two groups of infants, whose mothers previously received the tetanus-diphtheria-acellular pertussis vaccine (Tdap), were randomly vaccinated with either pentavalent or hexavalent vaccine at 2, 4, 6, and 18 months of age, following monovalent HB vaccine at birth. Blood samples were obtained at birth, one-month post-primary series immunization (mo 7), pre-booster (mo 18), one-month post-booster (mo 19), and six months post-booster (mo 24). The third group of infants, whose mothers did not receive Tdap, was vaccinated with DTwP-HB-Hib (EPI pentavalent group). Levels of HBsAg, anti-HBc, and anti-HBs were evaluated by means of an automated Chemiluminescent Microparticle Immunoassay.
Anti-HBs levels of ≥10 mIU/ml were achieved in 99.2% (hexavalent group), 99.2% (pentavalent group), and 98.5% (EPI pentavalent group) of infants, after four-dose immunization (at 0, 2, 4, 6 months of age). One month after the additional dose given at 18 months of age, anti-HBs levels of ≥10 mIU/ml were observed in 100% (hexavalent group), 99.2% (pentavalent group), and 93.8% (EPI pentavalent group) of infants. At 24 months of age, higher percentages of infants achieving anti-HBs levels ≥10 mIU/ml were found in the hexavalent group (98.3%) compared to the pentavalent group (86.5%).
Both vaccines were effective in inducing anti-HBs levels of ≥10 mIU/ml, and therefore either can be used as a single formula booster at 18 months of age to simplify vaccine administration under the Expanded Program on Immunization in Thailand.
Pregnant Thai women have low antibody titers against B. pertussis antigens, which coincide with an increasing incidence of pertussis among Thai infants. Thus, there exists a potential benefit of a ...booster dose of tetanus- diphtheria-acellular pertussis (Tdap) vaccine administered during pregnancy. Here, we report the vaccine reactogenicity profile and birth outcomes in Tdap-vaccinated pregnant women who have or have not had prior immunization with tetanus vaccine, and the IgG levels to B. pertussis antigens in maternal and cord sera at delivery.
Pregnant women (N = 370) aged 18–40 years were administered the Tdap vaccine (Boostrix®, GlaxoSmithKline, Rixensart, Belgium) at 26–36 weeks gestation. Adverse events following vaccination were identified by follow-up telephone call and medical record review. IgG against pertussis toxin (anti-PT), filamentous hemagglutinin (anti-FHA) and pertactin (anti-PRN) in both maternal and umbilical cord blood obtained at delivery were quantitatively evaluated using enzyme-linked immunosorbent assay (EUROIMMUN®, Lübeck, Germany).
There was no reported increase in the severity or duration of adverse events associated with the administration of an extra tetanus-containing vaccine within the previous five years (N = 181) or multiple doses of tetanus-containing vaccines during the current pregnancy (N = 98). Vaccination at least eight weeks prior to delivery resulted in high antibody titers to all B. pertussis antigens studied.
The reactogenicity of Tdap vaccine administered during pregnancy was not affected by prior tetanus toxoid immunization. High transplacental antibody against B. pertussis antigens in the cord blood provides evidence of antibody transfer and should thus help to protect newborns from pertussis during early life.
Background. Maternal vaccination with an acellular pertussis (aP)–containing vaccine is a recommended strategy in a growing number of industrialized countries, to protect young infants from disease. ...Little is known on the effect of this strategy in low- and middle-income countries. Following a previous report on the effect of adding a pertussis and diphtheria component to the tetanus vaccination program in pregnant women in Vietnam, we report on infant immune responses to a booster aP vaccine dose in this randomized controlled clinical trial. Methods. Thirty infants of Tdap (tetanus, diphtheria, and acellular pertussis)–vaccinated pregnant women and 37 infants of women vaccinated with a tetanus-only vaccine received a fourth aP-containing vaccine dose in the second year of life. Blood was taken 1 month after the fourth infant dose. Immunoglobulin G (IgG) antibodies against pertussis toxin (PT), filamentous hemagglutinin (FHA), pertactin (Prn), tetanus toxoid (TT), and diphtheria toxoid (DT) were measured using commercially available enzyme-linked immunosorbent assays (ELISA). Results. One month after the booster dose, significantly lower antibody titers were measured in the Tdap group for anti-TT IgG (P < .001) only. Anti-DT IgG, anti-PT IgG, anti-Prn IgG, and anti-FHA IgG antibody titers were comparable for both groups. A rise in antibody concentrations was elicited for all (except DT) antigens after boosting. Conclusions. The present results indicate that the blunting of infant pertussis responses induced by maternal immunization, measured after a primary series of aP vaccines, was resolved with the booster aP vaccine dose. These results add to the evidence for national and international decision makers on maternal immunization as a vaccination strategy for protection of young infants against infectious diseases.
Abstract
The varicella-zoster virus (VZV) infects >95% of the population. VZV reactivation causes herpes zoster (HZ), known as shingles, primarily affecting the elderly and individuals who are ...immunocompromised. However, HZ can occur in otherwise healthy individuals. We analyzed the immune signature and risk profile in patients with HZ using a genome-wide association study across different UK Biobank HZ cohorts. Additionally, we conducted one of the largest HZ human leukocyte antigen association studies to date, coupled with transcriptomic analysis of pathways underlying HZ susceptibility. Our findings highlight the significance of the major histocompatibility complex locus for HZ development, identifying 5 protective and 4 risk human leukocyte antigen alleles. This demonstrates that HZ susceptibility is largely governed by variations in the major histocompatibility complex. Furthermore, functional analyses revealed the upregulation of type I interferon and adaptive immune responses. These findings provide fresh molecular insights into the pathophysiology and activation of innate and adaptive immune responses triggered by symptomatic VZV reactivation.
Serological results obtained in a single laboratory from twin-studies on maternal immunisation, in Vietnam and Belgium offer the opportunity to compare antibody kinetics in infants before and after ...infant vaccination in the presence of vaccine-induced maternal antibodies. Nonlinear mixed-effects models (NLMMs) making use of a hypothesised dynamic evolution that captures the change in antibody titres over time, were employed to model anti-PT and anti-Prn antibody dynamics. Our proposed modelling approach provided useful insight into understanding the differences in the infants’ antibody kinetics in both countries since NLMMs offer the possibility of pooling all data in one analysis and incorporate relevant covariates of interest.
In both controlled cohort studies, pregnant women were vaccinated with a tetanus, diphtheria, acellular pertussis (Tdap) vaccine (Boostrix®, Belgium; Adacel®, Vietnam), and children were followed before and after primary vaccination, and before and after booster vaccination (Infanrix hexa®). From our models, both anti-PRN and anti-PT antibody titres at birth of Vietnamese infants were significantly lower than those of Belgian infants born to vaccinated women groups. Even though the antibody titres in the cord at birth of Belgian infants were also higher than those of Vietnamese infants born to the control women groups, the difference was not significant. The significant difference between infants born to vaccinated women in the two countries was likely due to the use of different vaccine brands in pregnant women and the different vaccination histories of women in these two countries.
Our analyses also suggested that the blunting effect was present during the primary immunisation but went away afterward for anti-PT data. In contrast, for anti-PRN antibodies, the blunting effect persisted after the primary vaccination and possibly went away after the booster dose. Countries should be aware of the regional situation in view of recommending maternal immunization.
Abstract
Introduction
Maternal antibody interference of the infant’s humoral immune responses raises some concern to the strategy of maternal Tdap (tetanus, diphtheria, acellular pertussis aP) ...vaccination. This study assessed the impact of maternal Tdap antibodies on the infant’s pertussis-specific T lymphocyte responses following infant vaccination with an aP containing vaccine, in a term and preterm born cohort.
Methods
Heparin samples (±0.5 mL) were conveniently drawn from infants of a Belgian prospective cohort study (N = 79, NCT02511327), including Tdap vaccinated (Boostrix®) and nonvaccinated women (no Tdap vaccine in the last 5 years) that delivered at term or prematurely. Sampling was performed before and 1 month after primary (8-12-16 weeks) and booster vaccination (13 or 15 months) with DTaP-IPV-HB-PRP~T vaccine (Hexyon®). Pertussis toxin (PT)-specific CD3+, CD3+ CD4+ and CD3+ CD8+ lymphoblasts and their cytokine secretions were measured using a flow cytometric assay on whole blood (FASCIA) and multiplex technology (Meso Scale Discovery), respectively.
Results
In total, 57% of all infants were considered PT-specific CD3+ CD4+ lymphoblasts responders after primary and booster vaccination, whereas 17% were CD3+ CD8+ lymphoblast responders. Interferon (IFN)-γ, interleukin (IL)-13, IL-17A, and IL-5 cytokine secretions after primary and booster vaccination were indicative of a mixed T helper (Th) 1/Th2/Th17 cell profile. Lymphoblast and cytokine levels were comparable between term and preterm infants. Nonresponders for IL-13 after booster vaccination had higher maternal PT immunoglobulin G (IgG) levels at birth when compared to responders.
Conclusions
Term and preterm born infants are capable of inducing Th1, Th2, and Th17 responses after aP vaccination, yet maternal vaccination modulate these responses. Evaluation of this effect in larger trials is needed.
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