Adacel® Booster Vaccination for CMI Assay Development

Study Overview
=================
Brief Summary
-----------------
Recruitment of individuals primed during childhood with TdaP (tetanus, diphtheria , acellular pertussis) vaccine, and administration of an Adacel booster with blood sample collection at various time points before and after vaccination. Collection of blood sample volumes will be large enough to allow assessment and comparison of multiple assays that evaluate cell-mediated immune (CMI) responses and other biomarkers following the administration of pertussis vaccinations. The ultimate objective would be to utilize these validated assays for evaluation of pertussis clinical trial results or development of new pertussis vaccine formulations.

Detailed Description
-----------------
Pertussis, known as whooping cough, is caused by the bacterium Bordetella pertussis which was discovered over a century ago. Human vaccines were developed in the subsequent two decades and routine childhood immunization has been practiced for over 60 years. Yet, B. pertussis remains a significant cause of morbidity in children and adults worldwide. Globally, about 20-40 million cases of pertussis are reported each year, with about 400,000 cases being fatal. The incidence of pertussis is highest and the severity the greatest in children under 6 months of age. Vaccination and natural infection are not protective for life, and the reason is unclear. The epidemiologic features of B. pertussis infections in older individuals who are only partially immune from prior infections and immunizations are not well understood. Clarification is important, in light of studies that suggest that pertussis is a cause of prolonged cough illness in adults who serve as the reservoir of B. pertussis and are the major source of infection for infants in whom the disease has substantial morbidity and mortality. With the considerable increase in cases and outbreaks, there is an imminent need for improved immunogenic and efficacious pertussis vaccines, paired with the best tools to evaluate vaccines and vaccine programs. VaxDesign has proposed two studies for acellular vaccine primed (acP) versus whole cell vaccine primed (wcP) donors, to further develop and validate a number of practical assays for use as biomarkers and to define a baseline readout for pertussis vaccinations from these two cohorts. In addition, these assays will be optimized to use the small blood volumes that are routinely available from clinical studies. In contrast to measuring humoral immune responses, the cell mediated immune response (CMI) is a substantially more challenging parameter to assess and thus the sample volumes required for the study must be large enough to allow the multiple different assessments. In this study, samples will be taken to evaluate transcriptomics, and humoral and cellular immunity over a one month period following vaccination. The collaboration with the Canadian Center for Vaccinology (CCfV) offers a unique opportunity of easily accessing acellular vaccine primed individuals.

Official Title
-----------------
Adacel® (TdaP-Tetanus, Diphtheria, Acellular Pertussis) Booster Vaccination of Acellular Pertussis Vaccine-primed Individuals for Cell Mediated Immunity Assay Development

Conditions
-----------------
Pertussis

Intervention / Treatment
-----------------
* Biological: Adacel®


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age ≥16years Primed during infancy with an acellular pertussis vaccine Good general health status, as determined by history no greater than 30 days prior to administration of the first test article Written informed consent provided If female of child-bearing potential, has a negative pregnancy test on the day of consent and has agreed to continue adequate contraception until after the last blood draw. Exclusion Criteria: Not primed in infancy with an acellular pertussis vaccine History of anemia Underlying chronic medical condition requiring ongoing monitoring by a physician (e.g., diabetes, seizure disorder) Underlying cardiac and/or pulmonary disease including hypertension, angina, prior myocardial infection, asthma, emphysema, chronic bronchitis, and pulmonary tuberculosis Pregnant (known before or established at the time of screening using a urine-based test) Immunocompromised (reporting HIV/AIDS positive or receiving immunosuppressive therapy involving steroids) Vaccinated against pertussis within previous 5 years Refusing to get an Adacel® (TdaP) vaccination dose

Ages Eligible for Study
-----------------
Minimum Age: 17 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Adacel®<br>All participants will receive one booster dose of commercially available Adacel® (TdaP-Tetanus, diphtheria, acellular pertussis) vaccine | Biological: Adacel®<br>* Vaccine for TdaP-Tetanus, diphtheria, acellular pertussis<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine best assay to evaluate CMI responses post-vaccination: CD4 T-cell proliferation | % CD4+CTV-T cells analyzed by flow cytometry | Days -14 to 28 | 
| Determine best assay to evaluate CMI responses post-vaccination: CD8 T-cell proliferation | % CD8+ CTV-T cells analyzed by flow cytometry | Days -14 to 28 | 
| Determine optimal time point for sample collection: CD4 T-cell responses | % CD4+CTV-cytokine+T cells analyzed by flow cytometry | Days -14 to 28 | 
| Determine optimal time point for sample collection: CD8 T-cell responses | % CD8+ CTV-cytokine+T cells analyzed by flow cytometry | Days -14 to 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Transcriptomic profiling of host - B. pertussis antigen interactions: B-cell plasmablasts | ASC per 106 PBMCs (ELISpot) | Days -7, 7, 14, and 28 | 
| Transcriptomic profiling of host - B. pertussis antigen interactions: B-cell plasmablasts | % CD19+ CD38+ CD27+ cells | Days -7, 7, 14, and 28 |