Abstract Vaccination of pregnant women with a pertussis containing vaccine is a recommended strategy in some industrialized countries, to protect young infants from severe disease. One of the effects ...of the presence of high titers of passively acquired maternal antibodies in young infants is blunting of immune responses to infant vaccination. We present infant immune responses to a fourth pertussis containing vaccine dose at 15 months of age, as a follow-up of previously presented data. In a prospective cohort study, women were either vaccinated with an acellular pertussis vaccine (Boostrix® ) during pregnancy (vaccine group) or received no vaccine (control group). All infants were vaccinated with Infanrix Hexa® according to the standard Belgian vaccination schedule (8/12/16 weeks, 15 months). We report results from blood samples collected before and 1 month after the fourth vaccine 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 ELISA tests. Antibody levels were expressed in International Units per milliliter. Demographic characteristics were similar in the vaccine and control group. Before the fourth vaccine dose, significantly lower antibody titers were measured in the vaccine group compared to the control group for anti-Prn IgG ( p = 0.003) and anti-DT IgG ( p = 0.023), with a steep decay of antibody titers since post-primary vaccination. One month after the fourth dose, antibody titers were only significantly lower in the vaccine group for anti-PT IgG ( p = 0.006). For all antigens, there was a rise in antibody titer after the fourth vaccine dose. The present results indicate still a minor blunting effect 1 month after a fourth vaccine dose for anti-PT antibodies. However, a good humoral immune response on all measured antigens was elicited in both groups of children. The clinical significance of such blunting effect is yet unknown. Clinicaltrials.gov identifier: NCT01698346.
Maternal immunization with a tetanus, diphtheria and acellular pertussis (Tdap) vaccine may blunt infant pneumococcal immune responses after a primary series of vaccines.
As part of a prospective ...controlled cohort trial of Tdap (Boostrix; GSK Biologicals, Rixensart, Belgium) vaccination in pregnancy, infants born to vaccinated mothers and controls were immunized at 8 and 16 weeks and 12 months of age with 13-valent pneumococcal conjugate vaccine (Prevenar13; Pfizer, Wyeth, United States). Sera were tested for pneumococcal antibody concentrations against vaccine serotypes following primary and booster immunization.
Geometric mean concentration of antibodies to serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14 and 19A was significantly lower after 2 doses of Prevenar13 vaccine in the offspring of the mothers vaccinated in pregnancy. This blunting effect disappeared after a booster dose at 12 months of age, except for serotypes 1 and 4. Despite this blunting, the percentage of children achieving the threshold of protection of 0.35 µg/mL was comparable in the vaccine and the control group both after primary and booster vaccination with only a significant lower rate of seroprotection in the vaccine group for serotype 3 after primary vaccination. After booster vaccination, seroprotection rates increased further for serotypes 3, 5, 6B, 9V and 23F.
The present results indicate a blunting effect after primary vaccination for some serotypes resolving after booster vaccination. Seroprotection rates were comparable both after primary and booster vaccination, except for serotype 3 with a significant lower seroprotection rate in the vaccine group after primary vaccination.
Abstract
Background
The blunting effect of pertussis immunization during pregnancy on infant antibody responses induced by whole-cell pertussis (wP) vaccination is not well-defined.
Methods
This ...randomized controlled trial (NCT02408926) followed term infants born to mothers vaccinated with tetanus, diphtheria, and acellular pertussis (Tdap) vaccine during pregnancy in Thailand. Infants received either acellular pertussis (aP)- or wP-containing vaccine at 2, 4, 6, and 18 months of age. A comparison group comprised wP-vaccinated children born to mothers not vaccinated during pregnancy. Antibodies against pertussis toxin (PT), filamentous hemagglutinin (FHA), and pertactin (PRN) were evaluated using commercial enzyme-linked immunosorbent assays. Functionality of antibodies against Bordetella pertussis was measured using Bordetella pertussis growth inhibition assay.
Results
After maternal Tdap vaccination, 158 infants vaccinated with aP-containing vaccines possessed higher antibody levels (P < .001) against all tested B. pertussis antigens postpriming compared to 157 infants receiving wP-containing vaccines. At 1 month postbooster, only anti-FHA and anti-PRN antibodies were still significantly higher (P < .001) in the aP group. Significantly higher anti-PT and anti-FHA (P < .001), but not anti-PRN immunoglobulin G, were observed among 69 wP-vaccinated infants born to control mothers compared with wP-vaccinated infants of Tdap-vaccinated mothers after primary and booster vaccination. The antibody functionality was higher in all wP-vaccinated infants at all times.
Conclusions
Maternal Tdap vaccination inhibited more pertussis-specific responses in wP-vaccinated infants compared to aP-vaccinated infants, and the control group of unvaccinated women had highest PT-specific responses, persisting until after the booster dose. Antibody functionality was better in the wP groups.
Clinical Trials Registration
NCT02408926.
Infant whole-cell pertussis (wP) vaccine responses are blunted after maternal Tdap vaccination. Pertussis antibody titers are higher in acellular pertussis (aP)– than wP-vaccinated infants of immunized mothers, yet quality of antibodies, measured as serum-mediated bacterial growth inhibition, is better after wP than aP vaccination.
Highlights • Maternal vaccination during pregnancy has a beneficial effect on the amount of sIgA in breast milk. • Breastfeeding after maternal vaccination results in a lower incidence of some ...infectious diseases in young infants. • The lack of a validated standardised assay for sIgA makes the research on immunoglobulin analyses in breast milk hard to interpret.
Abstract Vaccination of pregnant women is recommended for some infectious diseases in order to protect both women and offspring through high titres of maternal IgG antibodies. Less is known on the ...triggering of cellular immune responses by vaccines administered during pregnancy. In an ongoing study on maternal pertussis vaccination (2012–2014) 18 pregnant women were vaccinated with a tetanus-diphtheria-acellular pertussis (Tdap) containing vaccine (Boostrix®) during the third pregnancy trimester. Sixteen age-matched nonpregnant women received the same vaccine in the same time period. A blood sample was taken at the moment of, but before vaccination and one month and one year after vaccination. Anti-Pertussis Toxin (PT), filamentous hemagglutinin (FHA), pertactin (Prn), tetanus toxin (TT) and diphtheria toxin (DT) antibodies were measured by ELISA. Cellular immune responses were analyzed using a diluted whole blood assay, measuring proliferation, and cytokine release in response to vaccine antigens PT, FHA, TT, and to pokeweed mitogen (PWM) as polyclonal stimulus. Antibody levels to all five vaccine components increased significantly and to the same extent after vaccination in pregnant and nonpregnant women. One year after vaccination, antibody titres had decreased particularly to PT, but they were still significantly higher to all antigens than before vaccination. In contrast, proliferative and IFN-γ responses were increased to TT, PT, and FHA in nonpregnant women one month after vaccination, whereas in pregnant women only TT specific T cell responses were increased and to a lesser extent than in the control group. One year after vaccination, cellular responses equaled the baseline levels detected prior to vaccination in both groups. In conclusion, a Tdap vaccination can increase vaccine specific IgG antibodies to the same extent in pregnant and in nonpregnant women, whereas the stimulation of vaccine specific Th1 type cellular immune responses with this acellular vaccine is transient and impaired during pregnancy.
Vaccines protect humans against microorganisms that cause disease. Usually, vaccines are given to infants, toddlers, or older children at regular intervals. For example, you probably know about the ...tetanus vaccine, which is given to you when you are hurt, or beforehand, to protect you from disease in case you get hurt. Maternal immunization means vaccination of a woman during pregnancy. This can protect the pregnant woman and her unborn child from disease, and can also protect the new-born baby. The protection is provided by antibodies, which are substances made in the mothers’ body after vaccination, and are transported through the placenta and the breastmilk to the baby. Some vaccines are advised to be taken during pregnancy and, in the future, some vaccines might even be specifically designed to be used during pregnancy. This article will explain how vaccination during pregnancy works.
Vaccination of pregnant women protects both women and their newborns against some infectious diseases. Thailand implemented tetanus toxoid (TT) vaccination of pregnant women in 1977, which was ...replaced by tetanus–diphtheria toxoid (dT) vaccination in 2005. The tetanus–diphtheria–acellular pertussis (Tdap) vaccine has been recommended for pregnant women at 27–36 weeks of gestation since 2012 in several countries. Data on antibody responses to diphtheria toxoid (DT), TT, and Hemophilus influenzae type b (Hib) induced by combined vaccines in children born to TT-vaccinated and/or Tdap-vaccinated mothers are limited.
We investigated anti-DT, anti-TT, and anti-Hib IgG responses in a cohort of Thai children (ClinicalTrial.gov NCT02408926) born to mothers who received a TT-containing and/or the Tdap vaccine during pregnancy. Children born to Tdap-vaccinated mothers were randomized to receive either a hexavalent (Infanrix-hexa) or pentavalent (Quinvaxem) vaccine, whereas children born to TT-vaccinated mothers received only Quinvaxem vaccine at 2, 4, 6, and 18 months of age. IgG levels were evaluated at birth (cord blood), 2 (pre-primary), 7 (post-primary), 18 (pre-booster), and 19 months of age (post-booster) using a commercially available enzyme-linked immunoassay.
Seroprotective concentrations of anti-DT, anti-TT, and anti-Hib IgG were achieved in >90% and >99% of children following primary and booster vaccination, respectively. Among children born to Tdap-vaccinated mothers, the pentavalent vaccine induced higher levels of anti-Hib IgG than the hexavalent vaccine after primary and booster vaccination. Significantly higher anti-Hib IgG levels were observed among children receiving the pentavalent vaccine and who were born to TT-vaccinated mothers than among children receiving the pentavalent vaccine and born to Tdap-vaccinated mothers after primary and booster vaccination.
Vaccination with a TT-containing and/or the Tdap vaccine during pregnancy did not compromise the seroprotection rate achieved following primary and booster immunization in individuals receiving either the pentavalent or hexavalent vaccine.
Pertussis vaccination during pregnancy or immediately after delivery is a strategy that is increasingly being recommended to protect young infants from disease. Breast milk contains disease-specific ...antibodies that can contribute to the protection of young infants. The composition of breast milk could be altered by vaccination during pregnancy or near delivery. However, the quantification of these antibodies in breast milk lacks standardization.
In this paper, sample preparation procedures and detection methods for total and antipertussis toxin (anti-PT) secretory immunoglobulin (sIg) A are proposed that can be accurately repeated and are in accordance with European Medicines Agency and Food and Drug Administration requirements. Both antibody analytes were measured in breast milk samples of lactating women obtained 8-9 weeks postpartum to compare different maternal pertussis vaccination strategies: vaccination during pregnancy, shortly after or at delivery (cocoon), less than 5 years before delivery or more than 5 years before delivery.
The validated immunoassays could quantitatively detect total and anti-PT sIgA in the processed breast milk samples. Significantly higher levels of anti-PT sIgA were measured in breast milk after pertussis vaccination during pregnancy or at delivery geometric mean concentration (GMC): 2.56 and 2.15 IU/mg in contrast to mothers with no recent (>5 years) pertussis vaccination (GMC: 0.96 IU/mg; P = 0.014 and P = 0.028).
Vaccination against pertussis in the second/third trimester of pregnancy or immediately postpartum significantly increased the levels of anti-PT sIgA in breast milk.
Abstract
Background
Limited data exist on the impact of maternal tetanus, diphtheria, acellular pertussis (Tdap) vaccination for preterm born infants. We report its effect at birth and on ...antibody-mediated immune responses to a DTaP-IPV-HB-PRP~T vaccine in preterm compared with term infants.
Methods
Women delivering at term or prematurely were either vaccinated with a Tdap vaccine (Boostrix; GSK) during pregnancy or not vaccinated in the last 5 years. Cord and maternal blood were collected at delivery. Infants were vaccinated with DTaP-IPV-HB-PRP~T vaccine (Hexyon; Sanofi Pasteur) and blood collected before and 1 month after primary (8-12-16 weeks) and before and 1 month after booster vaccination (13 or 15 months for preterm and term, respectively). Immunoglobulin G antibodies against all antigens included in DTaP-IPV-HB-PRP~T vaccine were measured (NCT02511327).
Results
Cord blood geometric mean concentrations (GMCs) in preterm infants from Tdap-vaccinated women were significantly higher than in term and preterm infants from unvaccinated women. A longer time interval between maternal vaccination and delivery resulted in higher cord blood GMCs in preterm infants. Equal GMCs in term and preterm infants from Tdap-vaccinated women were observed after primary vaccination. After boosting, significantly lower GMCs were seen for pertussis toxin, filamentous hemagglutinin, and tetanus toxoid in preterm compared with term infants from Tdap-vaccinated women, yet still comparable to GMCs in both term and preterm infants from unvaccinated women.
Conclusions
Preterm infants profit from maternal Tdap vaccination. Prematurity did not influence primary immune responses in the presence of maternal antibodies but was associated with a lower booster immune response.
Preterm infants profit from maternal Tdap vaccination. Vaccination earlier in pregnancy is better to protect both term and preterm infants. Preterm infants mount favorable antibody-mediated immune responses in the presence of vaccine-induced maternal antibodies.
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