Study Evaluating SARS-CoV-2 (COVID-19) Humoral Response After BNT162b2 Vaccine in Immunocompromised Adults Compared to Healthy Adults

Study Overview
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Brief Summary
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The primary endpoint of this study is to compare the humoral response (titre and neutralizing capacity of induced antibodies) against SARS-CoV-2 following vaccination with BNT162b2 (Pfizer BioNTech) in immunocompromised persons, in comparison to healthy subject. Secondary objectives are to evaluate the humoral response in the nasal mucosa, and the capacity of antibodies to neutralize emerging variants of concerns and to prevent COVID-19.

Detailed Description
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The serious, even fatal, forms of COVID-19 preferentially affect elderly and fragile subjects. Among these populations at risk, people who are immunocompromised (either by a disease and / or its treatment) have a theoretical risk of responding less well to a preventive vaccination. The main objective of this study aims to compare the vaccine response of immunocompromised people with healthy subjects (non-immunocompromised), i.e. to assess the serum humoral response (titre and neutralizing capacity of the antibodies induced) following vaccination with ComirnatyTM (i.e. BNT162b2, an anti-SARS-CoV-2 vaccine from Pfizer BioNTech) in immunocompromised persons in comparison to healthy subjects (non-immunocompromised). Secondary objectives are as follows: To evaluate the antibody response in the nasal mucosa (titre and neutralizing capacity of the antibodies induced, collected by means of a nasopharyngeal swab) following vaccination with ComirnatyTM in immunocompromised people as compared to healthy subjects (vaccinated either with two doses of ComirnatyTM or, in a subgroup, with one dose of Astra Zeneca's VaxzeriaTM followed by one dose of ComirnatyTM). Evaluate the serum and mucosal antibody response (titre and neutralizing capacity of the antibodies induced) against emerging strains of SARS-CoV-2 (so-called Alpha, Beta, Gamma, Delta strains). Evaluate the post-vaccination clinical protection against the risk of COVID-19 infection (incident cases after vaccination).

Official Title
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Study Evaluating SARS-CoV-2 (COVID-19) Humoral Response After BNT162b2 Vaccine in Immunocompromised Adults Compared to Healthy Adults

Conditions
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Hiv, Kidney Transplant, Myeloma, Cancer, Hematologic Malignancy, Multiple Sclerosis, Hypergammaglobulinemia, Malignant Tumor, Diabetes Type 2

Intervention / Treatment
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* Biological: Biological samples


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult volunteers to be vaccinated with the ComirnatyTM vaccine and to participate in the study, belonging to one of the following groups: Group of immunocompromised (15 participants per immunosuppression subgroup): Kidney transplant Extracorporeal dialysis Solid cancer under chemotherapy and / or radiotherapy Myeloma under chemotherapy Hematologic malignancies under chemotherapy Diseases treated with anti CD20 (or patients not treated at the time of the vaccine but who will be immediately after) Multiple sclerosis under anti CD20 (or patients not treated at the time of the vaccine but who will be immediately after) Common variable immune deficiency or other causes of severe hypogammaglobulinemia requiring chronic treatment with polyvalent immunoglobulin Malignant tumor under anti-PD1 or anti-PDL1 People living with HIV Complicated type 2 diabetes (with micro and / or macroangiopathy) Group of non-immunocompromised subjects (controls, n = 75) 60 people vaccinated with the ComirnatyTM 15 people vaccinated with Astra Zeneca's VaxzevriaTM for the first dose Exclusion Criteria: Minors Pregnant or breastfeeding women Persons under tutorship or curatorship Protected adults Person under legal protection Person not affiliated to a social security scheme People with a contraindication to receiving the ComirnatyTM vaccine People who have already been vaccinated against SARS-CoV-2 Note: a history of COVID-19 (> at 3 months) is not a contraindication to vaccination and is therefore not a criterion for non-inclusion in the study.

Ages Eligible for Study
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Minimum Age: 18 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: Other
Intervention Model: Single Group Assignment
Interventional Model Description: All participants wil have at each of the 4 visits (for patients starting at month 1) or 5 visits (for patients starting at month 0): a venipuncture sample of 2 dry tubes of 7 mL (less than 30 mL in total) to make up 3 aliquots and a nasopharyngeal swab (optional). The aliquots of serum / plasma and the nasopharyngeal swab will be stored at -80°C until sent to the Pasteur Institute.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: immunocompromised and healthy subjects<br>Immunocompromised subjects and healthy subjects groups will have collection of biological samples (blood with/without nasopharyngeal swabs) at Month-0, -1, -2, -3, -6, with associated data for the study of the kinetics of antibodies anti COVID-19. Biological samples : Serum and plasma from each participant for the purpose of performing the SARS-CoV-2 serologic tests Nasopharyngeal samples (not mandatory) Associated data : Demographic data Description of clinical manifestations related to vaccination Description of clinical manifestations related to SARS-CoV-2 infection, if any Blood Fractioning Serum and plasma aliquoted and stored under 250, 500 and 1000 µL (at -80°C) | Biological: Biological samples<br>* Immunocompromised subjects and healthy subjects groups will have collection of biological samples (blood with/without nasopharyngeal swabs) at Month-0, -1, -2, -3, -6, with associated data for the study of the kinetics of antibodies anti COVID-19. Biological samples : Serum and plasma from each participant for the purpose of performing the SARS-CoV-2 serologic tests Nasopharyngeal samples (not mandatory) Associated data : Demographic data Description of clinical manifestations related to vaccination Description of clinical manifestations related to SARS-CoV-2 infection, if any Blood Fractioning Serum and plasma aliquoted and stored under 250, 500 and 1000 µL (at -80°C)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Protective humoral response after vaccination | Proportion of immunocompromised persons with neutralizing activity against the classic Wuhan strain of SARS-CoV-2 compared to the proportion obtained in healthy subjects. | Month 2 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mucosal neutralization capacity against wild-type and emerging variants of concern (VOC) | Proportion of immunocompromised people with neutralizing activity in the nasal mucosa against the classic Wuhan strain of SARS-CoV-2 compared to the proportion obtained in healthy subjects. | Month 0 | 
| Mucosal neutralization capacity against wild-type and emerging variants of concern (VOC) | Proportion of immunocompromised people with neutralizing activity in the nasal mucosa against the classic Wuhan strain of SARS-CoV-2 one month after the second dose of the vaccine, compared to the proportion obtained in healthy subjects. | Month 1 | 
| Mucosal neutralization capacity against wild-type and emerging variants of concern (VOC) | Proportion of immunocompromised people with neutralizing activity in the nasal mucosa against the classic Wuhan strain of SARS-CoV-2 compared to the proportion obtained in healthy subjects. | Month 2 | 
| Mucosal neutralization capacity against wild-type and emerging variants of concern (VOC) | Proportion of immunocompromised people with neutralizing activity in the nasal mucosa against the classic Wuhan strain of SARS-CoV-2 compared to the proportion obtained in healthy subjects. | Month 3 | 
| Mucosal neutralization capacity against wild-type and emerging variants of concern (VOC) | Proportion of immunocompromised people with neutralizing activity in the nasal mucosa against the classic Wuhan strain of SARS-CoV-2 compared to the proportion obtained in healthy subjects. | Month 6 | 
| Serum and nasal neutralization capacity against wild-type and emerging variants of concern (VOC) | Proportion of immunocompromised people with neutralizing activity in the serum and nasal mucosa against emerging strains of SARS-CoV-2 (so-called Alpha, Beta, Gamma, Delta strains) | Month 0 | 
| Serum and nasal neutralization capacity against wild-type and emerging variants of concern (VOC) | Proportion of immunocompromised people with neutralizing activity in the serum and nasal mucosa against emerging strains of SARS-CoV-2 (so-called Alpha, Beta, Gamma, Delta strains) | Month 1 | 
| Serum and nasal neutralization capacity against wild-type and emerging variants of concern (VOC) | Proportion of immunocompromised people with neutralizing activity in the serum and nasal mucosa against emerging strains of SARS-CoV-2 (so-called Alpha, Beta, Gamma, Delta strains) | Month 2 | 
| Serum and nasal neutralization capacity against wild-type and emerging variants of concern (VOC) | Proportion of immunocompromised people with neutralizing activity in the serum and nasal mucosa against emerging strains of SARS-CoV-2 (so-called Alpha, Beta, Gamma, Delta strains) | Month 3 | 
| Serum and nasal neutralization capacity against wild-type and emerging variants of concern (VOC) | Proportion of immunocompromised people with neutralizing activity in the serum and nasal mucosa against emerging strains of SARS-CoV-2 (so-called Alpha, Beta, Gamma, Delta strains) | Month 6 | 
| Clinical protection after vaccination | Proportion of participants developing COVID-19 infection after vaccination | Month 0 | 
| Clinical protection after vaccination | Proportion of participants developing COVID-19 infection after vaccination | Month 1 | 
| Clinical protection after vaccination | Proportion of participants developing COVID-19 infection after vaccination | Month 2 | 
| Clinical protection after vaccination | Proportion of participants developing COVID-19 infection after vaccination | Month 3 | 
| Clinical protection after vaccination | Proportion of participants developing COVID-19 infection after vaccination | Month 6 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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mucosa, immunocompromised, healthy subject, SARS-CoV-2, BNT162b2 vaccine, antibody, neutralization