Maternal vaccination: shaping the neonatal response to pertussis

Abstract

Antepartum maternal vaccination can protect highly sensitive newborns before they are old enough to receive their own vaccines. Two vaccines are currently recommended during pregnancy: the flu vaccine and the Tdap vaccine against tetanus, diphtheria, and pertussis. Although there is strong evidence that maternal vaccination works to protect the offspring, limitations in the understanding of vaccines and of maternal transfer of immunity compound to obscure our understanding of how they work. Here we focus on the example of pertussis to explore the possible mechanisms involved in the transfer of protection to offspring and how these may impact the newborn’s response to future exposure to pertussis. For example, Tdap vaccines induce pathogen specific antibodies, and those antibodies are known to be transferred from mother to the fetus in utero and to the newborn via milk. But antibodies alone have modest impact on pertussis disease, and even less effect on colonization/transmission. Maternal immune cells can also be transferred to offspring and may play a direct role in protection from disease and/or influence the developing neonatal immune system. However, some of the transferred immunity may also blunt the offspring’s response to subsequent vaccination. In this review we will summarize the protection conferred to offspring by maternal vaccination against pertussis and the likely mechanisms by which protection is transferred, identifying the many knowledge gaps that limit our most effective application of this approach.

Maternal Pertussis Immunization and Immunoglobulin G Levels in Early- to Late-Term and Preterm Infants

“…In this prospective cohort study, anti-PT IgG levels in term infants at 2 months of age following maternal Tdap vaccination between 20 0/7 and 24 0/7 weeks’ gestation were inferior to those in the group with Tdap vaccination between 30 0/7 and 33 0/7 weeks’ gestation, with an approximate 2-fold reduction in GMCs of anti-PT IgG levels. As long as the mechanisms of protection following maternal Tdap vaccination are not fully understood and no correlate of protection is available, anti-PT IgG levels are often used in studies like ours as surrogate markers for protection . Anti-PT levels in umbilical cord blood are correlated with protection against pertussis, and lower anti-PT IgG levels may point to less protection against pertussis in newborns.…”

“…As long as the mechanisms of protection following maternal Tdap vaccination are not fully understood and no correlate of protection is available, anti-PT IgG levels are often used in studies like ours as surrogate markers for protection. 18 Anti-PT levels in umbilical cord blood are correlated with protection against pertussis, 20 and lower anti-PT IgG levels may point to less protection against pertussis in newborns. We also observed a reduction in anti-Prn antibody levels after maternal Tdap vaccination between 20 and 24 weeks’ gestation compared with the reference group.…”

“…Anti-PT IgG antibody levels following maternal Tdap vaccination are associated with prevention of clinical pertussis. 18 Our primary outcome was to assess noninferiority of anti-PT antibody levels in term infants at 2 months of age following maternal Tdap vaccination between 20 0/7 and 24 0/7 weeks’ gestation compared with Tdap vaccination between 30 0/7 and 33 0/7 weeks’ gestation (reference cohort). The lower limit of the 95% CI of the geometric mean concentration ratio (GMR) between the main and the reference cohorts was set at 0.5 or greater for noninferiority.…”