Study to Evaluate the Immune Response After Booster Vaccination With Tdap-IPV Vaccine (Against Tetanus, Diphtheria, Pertussis and Poliomyelitis) in Children Who Received Different Pertussis Primary Vaccine Regimens in Republic of South Africa

Study Overview
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Brief Summary
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Primary Objectives : To describe the long-term humoral immune responses to pertussis, diphtheria, and tetanus after homologous and heterologous pertussis vaccine priming regimens To determine the effects of the priming regimen on humoral responses to booster vaccination with Tdap-IPV vaccine To describe the long-term cell-mediated immune responses to pertussis after homologous and heterologous pertussis vaccine priming regimens To determine the effects of the priming regimen on cell-mediated immune response to booster vaccination with Tdap-IPV vaccine Secondary Objective: To describe the safety profile of Tdap-IPV vaccine in each group

Detailed Description
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Study duration per participant will be approximately 30 days including: 1 day of screening and vaccination, a phone call and a safety follow-up/end of study visit, at Day 8 and Day 30 after vaccine administration, respectively.

Official Title
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Immune Response to Pertussis After Vaccination With a Tdap-IPV Booster Vaccine in Children in the Republic of South Africa: Effect of Homologous and Heterologous Pertussis Vaccination Priming Background

Conditions
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Pertussis Immunisation, Diphtheria Immunisation, Tetanus Immunisation, Poliomyelitis Vaccine

Intervention / Treatment
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* Biological: Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine Adsorbed Combined with Inactivated Poliomyelitis Vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Born in 2007 to 2011 in the RSA Received primary pertussis vaccination and the toddler booster in the RSA Assent form has been signed and dated by the participant, and informed consent form (ICF) has been signed and dated by the parent(s) or another legal guardian and by an independent witness, if required by local regulations Participants and parent/legal guardian are able to attend all scheduled visits and to comply with all trial procedures Valid clinical record of primary vaccination with DTaP/DTwP vaccines immunization history from 2007 through 2011, either by hand-held (Road-to-Health Card) or immunization clinical records For Groups 6 and 7: children infected with perinatally acquired HIV infection currently under care who received either an all wP or all aP priming regimen For Groups 6 and 7: be on highly active antiretroviral therapy (HAART) therapy and have known CD4 cell counts > 200 cells/µL Exclusion Criteria: Participation in the 4 weeks preceding the vaccination or planned participation during the present trial period in another clinical trial investigating a vaccine, drug, medical device, or medical procedure Receipt of any vaccine in the 4 weeks preceding the trial vaccination or planned receipt of any vaccine in the 4 weeks following the trial vaccination except for influenza Receipt of additional pertussis vaccination doses inconsistent with pertussis vaccination schedule in the RSA Previous confirmed diagnosis of pertussis disease Receipt of immune globulins, blood or blood-derived products in the past 3 months Known systemic hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to the vaccine used in the trial or to a vaccine containing any of the same substances For Groups 1 to 5: known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy, within the preceding 6 months; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months) Known thrombocytopenia, as reported by the parent/ legal guardian or suspected thrombocytopenia contraindicating intramuscular vaccination in the Investigator's opinion Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating intramuscular vaccination Participants with progressive neurological disorder, uncontrolled epilepsy, or progressive encephalopathy except if a treatment regimen has been established and the condition has stabilized Encephalopathy within 7 days of a previous dose of pertussis-containing vaccine Had contraindication to receipt of Adacel Quadra vaccine at the time of vaccination as defined in the Adacel Quadra vaccine Republic of South Africa (RSA) label Moderate or severe acute illness/infection (according to Investigator judgment) on the day of vaccination or febrile illness (temperature ≥ 38.0°C [≥ 100.4°F]). A prospective participants should not be included in the study until the condition has resolved or the febrile event has subsided (temporary contraindication) Receipt of oral or injectable antibiotic therapy within 72 hours prior to the first blood draw Note: Potential participants receiving standard HIV treatments such as antiretrovirals and/or antibiotic prophylaxis can be enrolled in the study. Their routine medications should be documented in the CRB. Identified as a natural or adopted child of the Investigator or employee with direct involvement in the proposed study

Ages Eligible for Study
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Minimum Age: 8 Years
Maximum Age: 14 Years

Sexes Eligible for Study
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All

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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1: Adacel Quadra vaccine<br>Adacel Quadra single injection at Day 0 in participants who received 4 doses of whole-cell pertussis (wP) vaccine during the first 2 years of life | Biological: Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine Adsorbed Combined with Inactivated Poliomyelitis Vaccine<br>* Pharmaceutical form:Suspension for injection Route of administration: Intramuscular<br>* Other names: Adacel®-Polio, Adacel Quadra®;|
| Experimental: Group 2: Adacel Quadra vaccine<br>Adacel Quadra single injection at Day 0 in participants who received 3 doses of wP followed by 1 dose of acellular pertussis (aP) vaccine during the first 2 years of life | Biological: Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine Adsorbed Combined with Inactivated Poliomyelitis Vaccine<br>* Pharmaceutical form:Suspension for injection Route of administration: Intramuscular<br>* Other names: Adacel®-Polio, Adacel Quadra®;|
| Experimental: Group 3: Adacel Quadra vaccine<br>Adacel Quadra single injection at Day 0 in participants who received 2 doses of wP vaccine followed by 2 doses of aP vaccine during the first 2 years of life | Biological: Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine Adsorbed Combined with Inactivated Poliomyelitis Vaccine<br>* Pharmaceutical form:Suspension for injection Route of administration: Intramuscular<br>* Other names: Adacel®-Polio, Adacel Quadra®;|
| Experimental: Group 4: Adacel Quadra vaccine<br>Adacel Quadra single injection at Day 0 in participants who received 1 dose of wP vaccine followed by 3 doses of aP vaccine during the first 2 years of life | Biological: Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine Adsorbed Combined with Inactivated Poliomyelitis Vaccine<br>* Pharmaceutical form:Suspension for injection Route of administration: Intramuscular<br>* Other names: Adacel®-Polio, Adacel Quadra®;|
| Experimental: Group 5: Adacel Quadra vaccine<br>Adacel Quadra single injection at Day 0 in participants who received 4 doses of aP vaccine during the first 2 years of life | Biological: Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine Adsorbed Combined with Inactivated Poliomyelitis Vaccine<br>* Pharmaceutical form:Suspension for injection Route of administration: Intramuscular<br>* Other names: Adacel®-Polio, Adacel Quadra®;|
| Experimental: Group 6: Adacel Quadra vaccine (HIV positive)<br>Adacel Quadra single injection at Day 0 in HIV + participants who received 4 doses of wP vaccine during the first 2 years of life | Biological: Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine Adsorbed Combined with Inactivated Poliomyelitis Vaccine<br>* Pharmaceutical form:Suspension for injection Route of administration: Intramuscular<br>* Other names: Adacel®-Polio, Adacel Quadra®;|
| Experimental: Group 7: Adacel Quadra vaccine (HIV positive)<br>Adacel Quadra single injection at Day 0 in HIV + participants who received 4 doses of aP vaccine during the first 2 years of life | Biological: Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine Adsorbed Combined with Inactivated Poliomyelitis Vaccine<br>* Pharmaceutical form:Suspension for injection Route of administration: Intramuscular<br>* Other names: Adacel®-Polio, Adacel Quadra®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Concentrations (GMCs) of anti-pertussis total immunoglobulin G (IgG) | Total IgG anti-pertussis antibody concentrations against the following pertussis antigens: pertussis toxin (PT), filamentous hemagglutinin (FHA), pertactin (PRN), and fimbriae types 2 and 3 (FIM) | Day 0 (pre-vaccination) and Day 30 (post-vaccination) | 
| GMCs of anti-diphtheria IgG | Total IgG anti-diphtheria antibody concentrations | Day 0 (pre-vaccination) and Day 30 (post-vaccination) | 
| GMCs of anti-tetanus toxoid IgG | Total IgG anti-tetanus antibody concentrations | Day 0 (pre-vaccination) and Day 30 (post-vaccination | 
| GMCs of anti-pertussis total immunoglubulin A (IgA) and of anti-heat-killed B pertussis (HK Bp) IgA in cell-mediated immunity (CMI) subset only | Total IgA anti-pertussis antibody concentrations against the following pertussis antigens: PT, FHA, PRN, FIM types 2 and 3, and heat-killed B. pertussis (HK Bp) | Day 0 (pre-vaccination) and Day 30 (post-vaccination) | 
| Geometric Mean (GM) of anti-pertussis IgG subclasses and of anti-HK Bp IgG subclasses. | Anti-pertussis IgG subclasses (ie, IgG1, IgG2, IgG3, and IgG4) distribution against PT, FHA, PRN, FIM types 2 and 3, and HK Bp | Day 0 (pre-vaccination) and Day 30 (post-vaccination) | 
| GM of pertussis antigen-specific T cells | Absolute numbers (spot forming cells [SFC]/10e6 PBMCs) of pertussis antigen-specific (antigen pool and HK Bp) interferon (IFN)-ɣ, interleukin (IL)-17, IL-4 secreting cells | Day 0 (pre-vaccination) and Day 30 (post-vaccination) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants reporting immediate adverse events (AEs) | Medically relevant unsolicited systemic AEs, including those related to the product administered | Within 30 minutes post-vaccination | 
| Number of participants reporting solicited injection site reactions and systemic reactions | Adverse reactions prelisted in the (electronic) case report book (CRB) Injection site reactions: pain, erythema, swelling Systemic reactions: fever, headache, malaise, myalgia | Within 7 days post-vaccination | 
| Number of participants reporting unsolicited AEs | AEs other than solicited reactions | Within 30 days post-vaccination | 
| Number of participants reporting serious adverse events (SAEs) | SAEs, including adverse event of special interest (AESIs) | Up to 37 days post-vaccination |