Comparative Study of Patterns of Immune Response to COVID 19 Vaccination

Study Overview
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Brief Summary
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An effective vaccine stands as the most effective way for controlling the COVID 19 pandemic , yet, immunogenic vaccine efficacy needs to be extensively studied . T cell responses against the structural proteins have been found to be the most immunogenic in peripheral blood mononuclear cells of convalescent SARS-CoV1 patients which needs to be tested in SARS -COV2 vaccine efficacy studies alongside with the sustainability of humoral and cellular immune responses . Clinically , immunocompromised patients face drastic outcome of infections , which led the Advisory Committee on Immunization Practices (ACIP) - USA -and the Joint Committee on Vaccination and Immunisation (JCVI) -UK- recommend COVID-19 vaccination of immunocompromised , the WHO Strategic Advisory Group of Experts on Immunization (SAGE), recommended that the three vaccines(Pfizer ,Moderna and Astra Zeneca) can be used for individuals with high-risk comorbidities . Nevertheless, there is an unmet research need concerning the immune response towards COVID 19 vaccination in this population . Based on the previous work of our team in designing B and T cell epitopes distributed over the S protein , we will study the immune response in the available vaccines in Egypt.

Detailed Description
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This proposed project is a joint collaboration between the National Research Center(NRC) , Hematology treatment unit of the holding company for biological products and vaccines (VACSERA) and Theodor Bilharz research institute . After a 1 month period of preparation , enrollment will start at month 2 (M2) over a 2 months enrollment window, where persons from 18-70 years old , of both sexes , having their first vaccination dose no more than 3 weeks of any of the available vaccines in Egypt will be enrolled into the project after signing an informed consent . Healthy persons not suffering from any systemic diseases will be enrolled from Theodor Bilharz vaccination center , and the Medical Researches Center of Excellence ( MRCE) at the NRC from the NRC vaccinated staff , while splenectomised B thalassemia patients will be enrolled from the hematology treatment unit at VACSERA . First visit will be performed 3 weeks post the first vaccination dose , while the second visit will be performed 3 weeks post the second vaccination dose , and the third visit will be performed 3 months post the second vaccination dose where ( 5 ) ml of blood will be withdrawn at each visit for the determination of the primary immune response at the first 2 visits and the sustainability of the immune response at the third visit . Enrolled persons will be instructed to contact the project logistics administrator upon experiencing any suspicious symptom of COVID 19 infection ( Fever- loss of taste and/or smell - myalgia - malaise - headache - diarrhea ) who will arrange for an additional visit where a PCR test for COVID 19 will be performed for the determination of breakthrough infections , and if positive this will be considered a primary end point and an additional ( 5) ml of blood will be withdrawn for testing for the immune status .

Official Title
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Comparative Study of Patterns of Immune Response to COVID 19 Vaccination Between Immunocompetent and Immunocompromised Subjects

Conditions
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Immune Response to Covid 19 Vaccination

Intervention / Treatment
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* Biological: Covid vaccines (Moderna - Pfizer- Astra Zeneca- Johnson and Johnson - Sinopahrm)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Both sexes. 3 weeks post scheduled first vaccination dose Healthy group not suffering from any systemic diseases. B thalassemia major splenectomized group Signing an informed consent . Exclusion Criteria: 1- Malignancy of whatever nature. 2- Systemic diseases apart from B thalassemia for the B thalassemia group. 3- Previous infection with COVID 19 . 4- Refusal to sign the informed consent . -

Ages Eligible for Study
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Minimum Age: 15 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Immunocompetent<br>100 healthy persons not suffering of any systemic diseases or malignancy of whatever nature. | Biological: Covid vaccines (Moderna - Pfizer- Astra Zeneca- Johnson and Johnson - Sinopahrm)<br>* Vaccination<br>|
| Immunocompromised<br>100 B thalassemia splenectomised patients. | Biological: Covid vaccines (Moderna - Pfizer- Astra Zeneca- Johnson and Johnson - Sinopahrm)<br>* Vaccination<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Studying the immune response to COVID -19 vaccination | Detection of total induced IgG binding antibodies | Month 3-Month 9 of the study | 
| . Comparing immune response to COVID 19 vaccination between healthy and immunocompromised groups |  | Month 3 - Month 9 of the study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| . Determination of the most immunogenic parts of COVID 19 vaccine | Detecting the most immunogenic epitopes located within the spike protein of the vaccines through ELispot assay | Month 3-Month 9 of the study |