Most childhood vaccines do not start providing adequate protection until the infant is several months old. The immunity gap between birth and this time can be addressed by maternal immunization.
Sex hormones modify immune responses:
- Increase in estradiol is associated with increased Th2 responses and reduced Th1 immune responses.
- Increased progesterone levels is associated with reduced immune response in general
- Overall phagocytic responses, alpha-defensin expression, neutrophil, monocyte and dendritic cell numbers may be increased in 2nd and 3rd trimester in general during preganacy.
- (may explain suboptimal responses to viral infections such as influenza in pregnancy)
- pregnancy is not a generalised state of immunosuppression.
Current recommendations are for pregnant women to have influenza and Tdap (tetanus-diphtheria-acellular pertussis) maternal immunisations
Influenza vaccine:
- Few low income countries regularly vaccinate pregnant women against influenza
- A substantial burden of illness among pregnant women is attributable to seasonal influenza
- The efficacy within infants after birth ranged from 30% to 63% (good for mom, ok for baby)
- There may be potential for protection against adverse birth outcomes, two studies detected a difference in low birth weight however the others did not. One study was sufficicnetly powered to detect a difference but the promising result was offset perhaps by the overall low baseline birth weight. So perhaps the vaccine is more useful as a protection against adverse outcomes.
- influenza infection is associated with an increased rate of subsequent bacterial infection particularly pneumococcal disease. (in fact a substantial proportion of deaths during the 1918 flu epidemic were probably due to strep.pneumoniae).
- use of maternal vaccine and infant vaccine together showed better results than infant vaccine alone in prevention of respiratory illnesses with fever and medically attended acute respiratory illnesses.
Pertussis vaccine:
- Young infants have a disproportionately high burden of severe pertussis in the population.
- studies on the pertussis vaccine have shown high effectiveness and a reassuring safety profile (there were no increaes in adverse birth or pregnancy outcomes).
- There was a slightly higher rate of chorioamnionitis but the authors explained this as perhaps due to practice of labelling fevers as chorioamnionitis to protect from litigation in the USA where the study was conducted
- There is concern though that the vaccine may reduce the immungenicity of the infant DTP (diphtheria-tetanus-pertussis) vaccine. With studies suggesting this, however the clinical relevance is uncertain.
Maternal vaccines in development include vaccines against RSV (respiratory syncytial virus) and GBS (group B streptococcus).
RSV vaccine:
- RSV is the leading cause of viral acute lower respiratory tract illness and the highest morbidity is among preterm infants. Most deaths due to RSV occur in infants
- 2-3% of all neonatal deaths are attributable to RSV.
- Vaccine is needed due to the high burden of RSV infection, particularly among young infants.
- Several RSV vaccines are in development, targeting the RSV F and G proteins mainly.
- Given that preterm infants are a high risk group, recommendation for the gestational age of vaccination will have to take into account adequate antibody transfer for preterm infants.
- In the 1960s a formalin inactivated form of the vaccine against RSV for children was researched. It led to an 'enhanced RSV disease', and increased rates and severity of RSV lower respiratory illness. Thought now to be due to a lack of protective antibodies being produced with an increase in CD4+ priming in the absence of CD8+ cells. This abherrent vaccine slowed further research into RSV vaccines.
- The benefit of a maternal vaccination is that it would bypass immunologic events that would lead to an enhanced RSV disease in infants.
Group B strep vaccine:
- Early onset GBS infection occurs in neonates younger than 7 days and is characterised by sepsis without a focus, pneumonia or meningitis.
- Late onset GBS infection occurs in infants who are 7 to 89 days of age and is characterised with higher rates of meningitis.
- Invasive GBS infection in pregnant women is associated with stillbirth
- GBS is transmitted from colonised mothers during birth (hence why there is universal maternal screening with intrapartum antibiotic prophylaxis).
- One in five pregnant women have evidence of GBS rectal or vaginal colonisation at 23-26 weeks.
- Screening with prophylaxis programmes mentioned above have resulted in reductions in early-onset GBS disease but NO reduction in late onset disease.
- A maternal GBS vaccine could help reduce the burden of GBS disease, particularly late-onset disease in infants.
- there is a trivalent vaccine in development that covers serotypes Ia, Ib and III. The global disease burden includes serotypes II and V, therefore a vaccine will need to be developed still to cover against also these subtypes
Incorporating maternal vaccines into antenatal care has been a challenge in many locations, with the maternal influenza vaccination rate in the US estimated to be around 50%.
Link to paper: http://www.nejm.org/doi/full/10.1056/NEJMra1509044
(all the points above and images were taken from the paper linked above)
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