Vaccine Responses in Infants After Acellular Pertussis Vaccination During Pregnancy in Thailand

Study Overview
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Brief Summary
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Young infants are most vulnerable to severe disease and even death when infected with Bordetella pertussis. The current vaccines and vaccination programs do not guarantee protection of neonates from this disease. Maternal acquired pertussis-specific antibodies show low concentrations with short persistence in newborns creating a susceptibility gap for infection between birth and the first vaccinations. A possible strategy to protect infants from birth is pertussis vaccination during pregnancy, which will increase the amount of passively transferred maternal antibodies. However, little is known regarding the effect of high titers of maternal antibodies on the infants immune responses to different pertussis vaccines (whole cell versus acellular). Humoral immune responses will be assessed in infants receiving whole cell versus infants receiving acellular pertussis vaccines. Functionality of the antibodies will also be analyzed.

Official Title
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Vaccine Responses in Infants After Acellular Pertussis Vaccination During Pregnancy in Thailand

Conditions
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Pertussis

Intervention / Treatment
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* Biological: Boostrix
* Biological: Infanrix hexa
* Biological: Quinvaxem
* Biological: OPV


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Willing to be immunized with a pertussis containing vaccine during pregnancy Intend to be available for follow-up visits and phone call through 19 months postpartum Willing to have infant immunized with a pertussis containing vaccine at 2, 4, 6 months and 18 months of age according to EPI (Expanded Programme of Immunization) and receiving (randomized) either acellular pertussis (aP) (study vaccine) or a whole cell pertussis (wP) vaccine. Consent for participation of the child is needed by both married parents or by a single unmarried other. At low risk for pregnancy related complications as determined by the investigator and a second trimester ultrasound with no significant abnormalities. Exclusion Criteria: Pregnant subjects Multiple pregnancies Serious obstetrical risk Serious underlying medical condition Significant mental illness History of febrile illness (greater than or equal to 38°C) within the past 72 hours before injection Previous severe reaction to any vaccine Receipt of tetanus-diphtheria toxoid immunization within the past 1 month Receipt of an pertussis containing vaccine (Tdap) in the last 5 years Receipt of a vaccine, blood product (excluding Rhogam) within the 4 weeks prior to injection through 4 weeks following injection and IVIG (Intravenous Immunoglobulins) within 12 weeks period. One month interval should be respected with another vaccine (except influenza) in orde to evaluate Adverse events following one or both vaccines (fever, local symptoms) Receipt of an experimental drug during pregnancy Anything in the opinion of the investigator that would prevent women from completing the study or put the woman at risk Infants Preterm delivery before 37 weeks of gestation Serious underlying medical condition Children suffering from primary humoral immune disorders; suffering from primary cellular immune deficiencies and disorders from the complete cascade No informed consent from one or both married parents Severe reactions to any vaccine Anything in the opinion of the investigator that would prevent children from completing the study or put the child at risk

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A<br>Women will be vaccinated with an acellular pertussis containing vaccine (Boostrix) between 27 and 36 weeks of gestation. Children born from these mothers will be vaccinated according to the official recommendations in Thailand at 2, 4, 6 and 18 months with a hexavalent acellular pertussis containing vaccine (Infanrix hexa). | Biological: Boostrix<br>* Pregnant women will be vaccinated with an acellular pertussis containing vaccine between 27 and 36 weeks of gestation.<br>* Other names: Acellular pertussis containing vaccine;Biological: Infanrix hexa<br>* Children from group A will be vaccinated with an acellular pertussis containing vaccine according to the official recommendations in Thailand at 2, 4, 6 and 18 months.<br>* Other names: Acellular pertussis containing vaccine;|
| Active Comparator: Group B<br>Women will be vaccinated with an acellular pertussis containing vaccine (Boostrix) between 27 and 36 weeks of gestation. Children born from these mothers will be vaccinated according to the official recommendations in Thailand at 2, 4, 6 and 18 months with a pentavalent whole cell pertussis containing vaccine (Quinvaxem). OPV (oral poliovirus vaccine) will also be administered at 2, 4, 6 and 18 months. | Biological: Boostrix<br>* Pregnant women will be vaccinated with an acellular pertussis containing vaccine between 27 and 36 weeks of gestation.<br>* Other names: Acellular pertussis containing vaccine;Biological: Quinvaxem<br>* Children from group B will be vaccinated with a whole cell pertussis containing vaccine according to the official recommendations in Thailand at 2, 4, 6 and 18 months.<br>* Other names: Whole cell pertussis containing vaccine;Biological: OPV<br>* Children from group B will be vaccinated with OPV vaccine according to the official recommendations in Thailand at 2, 4, 6 and 18 months.<br>* Other names: Oral Polio Vaccine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| kinetics of Pertussis toxin (PT) IgG titers in infants | Measurement of anti- Pertussis Toxin (PT) immunoglobulin (IgG) antibodies at several time points following maternal vaccination during pregnancy and after infant immunization (priming and boosting) with an acellular or whole cell pertussis containing vaccine | from birth until 19 months of age | 
| kinetics of Filamentous haemagglutinin (FHA) IgG titers in infants | Measurement of anti- Filamentous Haemmaglutinin (FHA) immunoglobulin (IgG) antibodies at several time points following maternal vaccination during pregnancy and after infant immunization (priming and boosting) with an acellular or whole cell pertussis containing vaccine | from birth until 19 months of age | 
| kinetics of Pertactin (Prn) IgG titers in infants | Measurement of anti- Pertactin (Prn) immunoglobulin (IgG) antibodies at several time points following maternal vaccination during pregnancy and after infant immunization (priming and boosting) with an acellular or whole cell pertussis containing vaccine | from birth until 19 months of age | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Functionality of the maternal anti-PT IgG antibodies in the infants as assessed with a newly validated luminescence based assay | functionality of the passively acquired anti-PT antibodies in infants following maternal vaccination during pregnancy with an acellular pertussis containing vaccine (Boostrix), as assessed with a newly validated luminescence based assay | At birth | 
| Functionality of the anti-PT IgG antibodies in the infants after vaccination assessed with a newly validated luminescence based assay | To measure the functionality of the anti-PT antibodies in infants vaccinated with either an acellular pertussis containing vaccine (Infanrix hexa) or a whole cell pertussis vaccine (Quinvaxem), after maternal vacicnation during pregnancy, assessed with a newly validated luminescence based assay | At month 7 and month 19 | 
| Efficacy of the transplacental transport of IgG as assessed by the ratio of cord and maternal titers of IgG antibodies | Efficacy as assessed by the ratio of cord and maternal titers of IgG antibodies | Birth | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Humoral immune response, Pertussis, Pregnancy, Functionality, Vaccination