Immunizing pregnant women to protect the mother, fetus and infant from infection has increasingly been used over the last decade. Protection against infectious diseases in neonates is mainly provided ...by maternal antibodies transferred from mother to infant during pregnancy through transplacental transport or after delivery via breastfeeding. Both the transplacental- and breast milk–derived maternal antibodies function as the primary source of protection against infectious diseases in neonates during the first vulnerable weeks of life. During recent infectious disease outbreaks (influenza, pertussis, Zika…) and for other infectious diseases (CMV, GBS…), pregnant women are increasingly identified as an important target for vaccination. For some of these diseases, vaccines are already on the market, and recommended during pregnancy. For others, vaccines are currently under development; furthermore, some are even specifically designed to be administered during pregnancy.
Conclusion
: This review article provides an overview on the rationale and main mechanism of the maternal vaccination strategy and gives a summary about the current and possible future recommendations for maternal vaccination.
What is Known:
•
Maternal vaccination has a far-reaching potential in the protection of both women and offspring.
• Currently, tetanus, pertussis and influenza vaccination during pregnancy is recommended in some countries. Several new vaccines specifically designed for use in pregnancy are currently under development.
What is New:
•
Review providing a timely overview of the rationale and main mechanisms of the maternal vaccination strategy
• Up-to-date summary of the current and possible future recommendations for maternal vaccination
Abstract A pertussis vaccination during pregnancy has recently been adopted in several countries to indirectly protect young infants. This study assessed the effect of adding a pertussis component to ...the tetanus vaccination, in the pregnancy immunization program in Vietnam. A randomized controlled trial was performed. Pregnant women received either a Tdap (tetanus, diphtheria acellular pertussis) vaccine or a tetanus only vaccine between 19 and 35 weeks’ gestational age. Immunoglobulin G (IgG) against tetanus (TT), diphtheria (DT), pertussis toxin (PT), filamentous hemaglutinin (FHA) and pertactin (Prn) were measured using commercial ELISA tests, at baseline, 1 month after maternal vaccination, at delivery, and in infants from cord blood and before and after the primary series (EPI: month 2-3-4) of a pertussis containing vaccine. Significantly higher geometric mean concentrations (GMC) were observed for all 3 measured pertussis antigens in the offspring of the Tdap group, up to 2 months of age. One month after completion of the primary infant vaccination schedule, anti-Prn GMC, but not anti-PT and anti-FHA GMCs, was significantly ( p = 0.006) higher in the control group. Maternal antibodies induced by vaccination during pregnancy close the susceptibility gap for pertussis in young infants. Limited interference with the infant vaccine responses was observed. Whether this interference effect disappears with the administration of a fourth vaccine dose is further studied.
Tetanus, diphtheria, acellular pertussis (Tdap) vaccination is recommended to be administered in every pregnancy. Although the safety of this strategy has been confirmed, the immunogenicity of Tdap ...vaccination in two successive pregnancies has not yet been described. This study investigated Tdap-specific immunity levels and transplacental transfer in two successive pregnancies after repeated Tdap-vaccination.
Women enrolled in prior studies on Tdap vaccination during pregnancy were invited to participate in a follow-up study if they became pregnant again. Women who received a Tdap vaccine in both pregnancies were considered for this analysis. Tdap-specific total IgG and IgG subclasses were measured with a multiplex immunoassay.
In total, 27 participants with a mean interval between deliveries of 2.4 years were included in the analysis. In maternal serum, Tdap-specific total IgG levels were comparable at both deliveries whereas in cord serum, all Tdap-specific total IgG antibody levels were reduced at the second compared to the first delivery. This was largely reflected in the IgG1 levels in maternal and cord serum. Transplacental transfer ratios of total IgG and IgG1 were also mostly reduced in the second compared to the first pregnancy.
This study reports for the first time Tdap-specific total IgG and IgG subclass levels and transfer ratios after repeated Tdap vaccination in successive pregnancies. We found reduced transfer of most Tdap-specific IgG and IgG1 antibodies in the successive pregnancy. As pertussis-specific antibodies wane quickly, Tdap vaccination in each pregnancy remains beneficial. However, more research is needed to understand the impact of closely spaced booster doses during pregnancy on early infant protection against pertussis.
Characteristics of the human neonatal immune system are thought to be responsible for heightened susceptibility to infectious pathogens and poor responses to vaccine antigens. Using cord blood as a ...source of immune cells, many reports indicate that the response of neonatal monocytes and dendritic cells (DC) to Toll-like receptor (TLR) agonists differs significantly from that of adult cells. Herein, we analyzed the evolution of these responses within the first year of life.
Blood samples from children (0, 3, 6, 9, 12 month old) and healthy adults were stimulated ex vivo with bacterial lipopolysaccharide (LPS, TLR4 agonist) or CpG oligonucleotides (TLR9 agonist). We determined phenotypic maturation of monocytes, myeloid (m) and plasmacytoid (p) DC and production of cytokines in the culture supernatants. We observed that surface expression of CD80 and HLA-DR reaches adult levels within the first 3 months of life for mDCs and 6-9 months of life for monocytes and pDCs. In response to LPS, production of TNF-alpha, IP-10 and IL-12p70 reached adult levels between 6-9 months of life. In response to CpG stimulation, production of type I IFN-dependent chemokines (IP-10 and CXCL9) gradually increased with age but was still limited in 1-year old infants as compared to adult controls. Finally, cord blood samples stimulated with CpG ODN produced large amounts of IL-6, IL-8, IL-1beta and IL-10, a situation that was not observed for 3 month-old infants.
The first year of life represents a critical period during which adult-like levels of TLR responses are reached for most but not all cytokine responses.
In Flanders, Belgium, pertussis vaccination is recommended since 2013 and available free-of-charge in every pregnancy between 24 and 32 weeks of gestation. Influenza vaccination is recommended for ...more than 10 years with a co-payment system in the second or third trimester of pregnancy, when pregnancy coincides with the influenza season. This study aims to estimate the coverage of pertussis and influenza vaccination during pregnancy in 2016 and to determine predictors for missing vaccination.
Postpartum women were visited at home for a vaccination coverage survey using an Expanded Program on Immunization (EPI)-based two-stage cluster sampling design. Predictors for missed vaccination were identified using a multiple logistic regression model.
Among 481 participating women, 69.3% were vaccinated against pertussis and 47.2% were vaccinated against influenza. Moreover, 65.3% of pertussis vaccine recipients and 96.9% of influenza vaccine recipients were vaccinated within the recommended gestational window.
Surprisingly, among women who were completely informed (i.e. on disease-associated risks, maternal vaccination costs and recommendations), still 12.4% were unvaccinated against pertussis and 23.9% against influenza.
In the final models, the only common predictor of missing maternal pertussis and influenza vaccination was multiparity. Significant predictors of maternal pertussis vaccination were family income (less likely if unknown or low (< €3000) than if moderate (€3001-€4000)) and hospital of delivery (less likely if >800 annual deliveries than <800). Significant predictors of maternal influenza vaccination, though with less straight-forward associations, were maternal ethnicity and educational level, involvement of a gynaecologist in pregnancy follow-up, and characteristics of the hospital of delivery.
In Flanders, more than two-third of pregnant women receives pertussis vaccination but less than half of them receives the influenza vaccine. Further improvement for both maternal vaccination programs can be achieved by targeting the underserved populations and diminishing vaccination hurdles.
Background
Pertussis vaccination during pregnancy is an effective strategy at reducing pertussis-related morbidity and mortality in infancy and is recommended across several countries. However, the ...optimal timepoint for vaccination in pregnancy to afford maximal protection to newborns is yet to be elucidated. This multi-country analysis aimed to model the impact of timing of vaccination during pregnancy on infant antibody titers at birth.
Methods
A multi-country analysis on a cohort of mother-infant pairs (n=698) vaccinated between 19.6-37.1 weeks gestation was conducted. Data taken from four parent studies on pertussis vaccination during pregnancy were modelled using natural cubic splines and linear mixed models to study the association of both gestational age at vaccination and the interval between vaccination and delivery with pertussis-specific cord blood antibody levels after pertussis vaccination during pregnancy.
Results
Term born infants on average achieve the highest antibody levels at birth if women are vaccinated before 31 weeks’ gestation. When considering both term and preterm deliveries, an interval of at least 7.5 weeks between vaccination and delivery is required to achieve the highest cord blood antibody levels. The models show that vaccinating earlier than these timeframes will also provide the infant with equally high antibody levels at birth.
Conclusions
Vaccinating in the second and early third trimester results in the highest antibody levels at birth. Vaccinating earlier within this window is needed to provide equal benefits to both term and preterm born infants.
Immunization with tetanus-diphtheria-acellular pertussis (Tdap) vaccine in pregnancy is increasingly recommended. We determined the effect of Tdap immunization in pregnancy on infants' vaccine ...responses.
Individual-participant data meta-analysis of ten studies (n=1884) investigating infants' antibody response to routine immunizations following Tdap immunization in pregnancy was performed. Geometric mean ratios (GMRs) of antigen-specific immunoglobulin G (IgG) levels were calculated using mixed-effects models. Seroprotection rates were compared using chi-squared tests.
Infants of Tdap-immunized women had significantly lower IgG against pertussis toxin (GMR 0.65; 95%CI 0.57-0.74), filamentous haemagglutinin (FHA) (0.68; 0.53-0.87), pertactin (0.65; 0.58-0.72) and fimbria 2/3 (FIM2/3) (0.41; 0.32-0.52) after primary immunization, compared with infants of unimmunized women. These lower levels persisted after booster immunization for FHA (0.72; 0.61-0.84) and FIM2/3 (0.53; 0.29-0.96). After primary immunization, infants of Tdap-immunized women had lower seroprotection rates against diphtheria (90% 843/973
98% 566/579; p<0.001) and invasive pneumococcal disease (IPD) caused by 5
(SPN) serotypes (SPN5, SPN6B, SPN9V, SPN19A, SPN23F), and higher seroprotection rates against
type b (short-term and long-term seroprotection rates, 86%471/547
76%188/247 and 62%337/547
49%(121/247), respectively, all p=0.001). After booster immunization, seroprotection rates against diphtheria and tetanus were 99% (286/288) and (618/619) in infants of Tdap-immunized women, respectively.
Infants of Tdap-immunized women in pregnancy had lower IgG levels against pertussis, diphtheria and some SPN serotypes after their immunization compared with infants of unimmunized women. Enhanced surveillance of pertussis, diphtheria and IPD in infants is needed to determine the clinical significance of these findings.
CRD42017079171.
Highlights • Pertussis vaccination in pregnancy is safe, immunogenic and effective. • The strategy is accepted by the target population and the health care workers. • Remaining knowledge gaps include ...(among others): optimal timing of the booster dose, and detailed immunological background on the role and function of maternal antibodies.
To examine the influence of a pertussis booster vaccination on the transfer of maternal antibodies, 24 nonpregnant women received a tetanus, diphtheria, acellular pertussis booster vaccine between 2 ...consecutive pregnancies. Blood was drawn from mothers and off-spring. Efficient transplacental antibody transfer and significantly higher antibody titers against 3 pertussis antigens were observed in cord blood and in blood of 1-month-old infants born after a maternal booster vaccination compared with results in their siblings born before the booster administration.
Maternal antibodies induced by vaccination during pregnancy cross the placental barrier and can close the susceptibility gap to pertussis in young infants up to the start of primary immunization. As ...not only the quantity but also the quality of circulating antibodies is important for protection, we assessed whether maternal immunization affects the avidity of infant vaccine-induced IgG antibodies, in the frame of a prospective clinical trial on pregnancy vaccination in Belgium. Infants born from Tdap (Boostrix®) vaccinated (N = 55) and unvaccinated (N = 26) mothers were immunized with a hexavalent pertussis containing vaccine (Infanrix Hexa®) at 8, 12 and 16 weeks, followed by a fourth dose at 15 months of age. Right before and one month after this fourth vaccine dose, the avidity of IgG antibodies against diphtheria toxin (DT), tetanus toxin (TT), pertussis toxin (PT), filamentous hemagglutinin (FHA) and pertactin (Prn) was determined using 1.5 M ammonium thiocyanate as dissociating agent.
In both groups, antibody avidity was moderate for TT, PT, FHA and Prn and low for DT after priming. After a fourth dose, antibody avidity increased significantly to high avidity for TT and PT, whereas it remained moderate for FHA and Prn and low for DT. The avidity correlated positively with antibody level in both study groups, yet not significantly for PT. When comparing both study groups, only PT-specific antibodies showed significantly lower avidity in infants born from vaccinated than from unvaccinated mothers after the fourth vaccine dose. The clinical significance of lower avidity of vaccine induced infant antibodies after maternal vaccination, if any, needs further investigation.
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