Maternal Antibody in Milk After Vaccination

Study Overview
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Brief Summary
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Single-centre observational pilot study exploring pertussis specific antibody concentration in the breastmilk of women vaccinated against pertussis in pregnancy at different gestational ages. This study is made up of two stages: first stage to confirm recruitment methods and optimise the laboratory assay and a second stage to complete recruitment for the pilot study.

Detailed Description
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Pertussis disease is a highly infectious respiratory illness caused by Bordetella pertussis, which can cause significant morbidity and mortality. There has been an increase in cases in many high income countries with high vaccination coverage and in an attempt to control this, antenatal vaccination programmes have been introduced in several countries, including the UK. Vaccination in pregnancy is a strategy which seeks to boost the maternal antibody levels, increase the placental transfer of antibody and consequently increase the antibody levels in the infant. Human breast milk is a dynamic source of nutrition for the infant and is made up of many immunologically active components including antibody. The principal antibody in breastmilk is IgA and it has been shown that the amount of disease specific antibody in breastmilk can be increased by vaccination in pregnancy for a number of pathogens including pertussis. Secretory IgA (sIgA) plays an important role in immune exclusion in which it blocks adhesion of a pathogen onto a mucosal surface. As the first step of pertussis pathogenesis is the adhesion of bacteria to the ciliated respiratory epithelium in the nasopharynx and trachea there is a clear biological rationale for the hypothesis that receiving breast milk containing more IgA could enhance neonatal immunity and consequently the protective effects of vaccination in pregnancy. The best time in pregnancy for administering the pertussis vaccination is debated in the literature, with some advocating vaccination in the second trimester and others supporting later vaccination to coincide the time of serum antibody peak with optimum placental transfer. This issue has been considered exclusively from the perspective of serum immunoglobulin G (IgG), but the impact of timing of vaccination in pregnancy on IgA levels in milk may also be important. Previous studies have shown that there is a peak in the pertussis specific IgA in breast milk at day 10 following vaccination, which then declines, and consequently there may be a significant difference in the amount of IgA available in the breastmilk for an infant born to a mother vaccinated at 20 weeks for example, compared to a mother vaccinated at 32 weeks. This may therefore have an impact on future guidelines on optimal time of vaccination in pregnancy.

Official Title
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Maternal Antibody in Milk After Vaccination

Conditions
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Pertussis, Vaccination, Pregnancy, Breastmilk

Intervention / Treatment
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* Biological: Boostrix-IPV


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Singleton pregnancy Received pertussis vaccination between 16 and 32 gestational weeks Planning to breastfeed Exclusion Criteria: Received vaccination outside of the 16-32 week window Not planning to breastfeed Diagnosis of an immunodeficiency syndrome Multiple pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Women vaccinated at less than 24 weeks<br>Women receiving a pertussis containing vaccine at less than 24 weeks | Biological: Boostrix-IPV<br>* Receipt of Boostrix IPV at three different gestational time periods<br>|
| Women vaccinated at 24-27+6 weeks<br>Women receiving a pertussis containing vaccine at 24-27+6 weeks | Biological: Boostrix-IPV<br>* Receipt of Boostrix IPV at three different gestational time periods<br>|
| Women vaccinated at 28-31+6 weeks<br>Women receiving a pertussis containing vaccine at 28-31+6 weeks | Biological: Boostrix-IPV<br>* Receipt of Boostrix IPV at three different gestational time periods<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anti PT IgA at less than 48 hours in colostrum | Anti-pertussis toxin (PT) Immunoglobulin A (IgA) concentration in colostrum | Within 48 hours of delivery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total IgA and IgG in colostrum and breastmilk | Total IgA and IgG concentration in colostrum and breastmilk | Within 48 hours and at 14 and 42 days after delivery | 
| Anti-PT IgA concentration in breastmilk | Anti-PT IgA concentration in breastmilk | At 14 and 42 days following delivery | 
| Anti-PT IgG concentration in colostrum and breastmilk | Anti-PT IgG concentration in colostrum and breastmilk | Within 48 hours and at 14 and 42 days after delivery | 
| Anti PT IgG concentration in maternal serum | Anti PT IgG concentration in maternal serum | Within 48 hours of delivery |