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

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.

Background Limited data exist on the impact of maternal Tetanus, Diphtheria, acellular Pertussis (aP) (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 to 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 bled before and one month after primary (8-12-16 weeks) and before and one 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 PT, FHA and TT in preterm compared to term infants from Tdap-vaccinated women, yet still comparable to GMCs in both term and preterm infants from unvaccinated women. Conclusion 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.

Introduction/Background & Aims Enrichment of breast milk (BM) with immunoglobin (Ig)A and IgG, through maternal vaccination, could help young infants combat targeted pathogens. However, evidence on this effect after preterm delivery is lacking. This study investigated the total and anti-pertussis toxin (anti-PT) specific IgA and IgG production in BM after term or preterm delivery in the presence of maternal Tdap (tetanus, diphtheria, acellular pertussis) vaccination. Methods 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, NCT02511327). Anti-PT IgA/IgG (IBL®; MSD®) and Total IgA/IgG (Thermofisher®, on BM samples only) immunosorbent assays were performed on all samples collected at 72 hours, 4, 8, and 12 weeks postpartum. Results BM after preterm delivery contained anti-PT IgA and IgG geometric mean concentrations (GMCs) comparable to those after term delivery (e.g. colostrum anti-PT IgA: 5.39 International Units per milliliter (IU/mL) vs 6.69 IU/mL, respectively). Maternal Tdap vaccination induced significantly higher anti-PT IgG GMC’s in colostrum of vaccinated compared to unvaccinated women delivering at term (0.110 IU/mL vs 0.027 IU/mL, p=0.009). Compliance with postpartum vaccination led to no differences in BM after 4 weeks postpartum. Anti-PT antibodies persisted up to 12 weeks postpartum. Conclusions 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.

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 (±0.5mL) were conveniently drawn from infants of a Belgian prospective cohort study (N=79, NCT02511327), including Tdap vaccinated (Boostrix®) and non-vaccinated women (no Tdap vaccine in the last 5 years) that delivered at term or prematurely. Sampling was performed before and one 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 57% of all infants were considered PT-specific CD3 +CD4 + lymphoblasts responders after primary and booster vaccination, whereas 17% were CD3 +CD8 + lymphoblast responders. IFN-γ, 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. Non-responders for IL-13 after booster vaccination had higher maternal PT 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.