COVID-19 Vaccine Responses in PIDD Subjects

Study Overview
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Brief Summary
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The goal of our study is to assess the cellular immune responses of participants with antibody deficiency disease before and after immunization with SARS-CoV-2 mRNA vaccines.

Detailed Description
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Individuals with primary and secondary antibody immunodeficiency are at higher risk for severe COVID-19 disease. Humoral immunity is thought to be the predominant protection against COVID-19, however mRNA vaccines have been shown to elicit both antibody and cellular responses. The goal of our study is to assess the cellular immune responses of participants with antibody deficiency diseases, including X-linked agammaglobulinemia (XLA), common variable immunodeficiency (CVID), and secondary hypogammaglobulinemia, before and after immunization with SARS-CoV-2 mRNA vaccines. Our aim is to examine SARS-CoV-2 spike-specific T cell immune responses before and after immunization with mRNA vaccines in a cohort of individuals with antibody deficiencies compared to healthy volunteers. Our secondary objectives include (1) detecting cellular immune response differences between immunized and infected participants, (2) observing cellular immune responses over time, and (3) comparing clinical outcomes between vaccination, infection, and underlying antibody deficiency. The results will show whether antibody deficiency individuals can mount T cell responses to SARS-CoV-2 vaccination or infection, data that are expected to inform health policy of SARS-CoV-2 implementation in immunocompromised individuals. Findings will further provide foundation for larger cohort studies of SARS-CoV-2 vaccination in other immunocompromised populations.

Official Title
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Vaccine-induced SARS-CoV-2-specific T Cell Responses in Patients With Primary Immune Deficiency Disease

Conditions
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X-linked Agammaglobulinemia, XLA, Primary Immune Deficiency, CVID, Common Variable Immunodeficiency, Primary Antibody Deficiencies, Secondary Hypogammaglobulinemia

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of antibody deficiency with confirmatory lab or genetic testing Stable on immunoglobulin replacement therapy Age >5 years and able to provide consent, or assent with parental consent if <18 years Willing and able to receive the Pfizer BioNTech BNT162b2 mRNA or the Moderna mRNA-1273 vaccines Exclusion Criteria: (1) History of other chronic disease with depressed immune function or immune suppressive medication

Ages Eligible for Study
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Minimum Age: 5 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| X-linked agammaglobulinemia (XLA)<br>This study is a non-randomized observational cohort study of participants with XLA who have either received, as standard care, the Pfizer BioNTech BNT162b2 mRNA vaccine or the Moderna mRNA-1273 vaccine. In this protocol, vaccination is entirely voluntary and vaccines are not provided by the study. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Spike (S) protein-specific T cell responses to stimulation with SARS-CoV-2 wild-type peptides (measured as a percentage of total T cells). |  | 2 years | 
| Spike (S) protein-specific T cell responses to stimulation with SARS-CoV-2 alpha variant peptides (measured as a percentage of total T cells). |  | 2 years | 
| Spike (S) protein-specific T cell responses to stimulation with SARS-CoV-2 beta variant peptides (measured as a percentage of total T cells). |  | 2 years | 
| Spike (S) protein-specific T cell responses to stimulation with SARS-CoV-2 delta variant peptides (measured as a percentage of total T cells). |  | 2 years | 
| Spike (S) protein-specific T cell responses to stimulation with SARS-CoV-2 omicron variant peptides (measured as a percentage of total T cells). |  | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| S-specific T cell responses (as a percentage of total T cells) to SARS-CoV-2 vaccination in primary antibody deficiency over time. |  | 2 years | 
| S-specific T cell responses (as a percentage of total T cells) to SARS-CoV-2 vaccination in secondary antibody deficiency over time. |  | 2 years | 
| S-specific T cell responses (as a percentage of total T cells) to SARS-CoV-2 in infected participants. |  | 2 years | 
| S-specific T cell responses (as a percentage of total T cells) to SARS-CoV-2 in vaccinated participants. |  | 2 years | 
| Number of vaccinated participants who develop severe COVID-19 clinical outcomes. |  | 2 years | 
| Number of infected participants who develop severe COVID-19 clinical outcomes. |  | 2 years | 
| Number of antibody deficiency participants who develop severe COVID-19 clinical outcomes. |  | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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X-linked Agammaglobulinemia, Primary Immune Deficiency, Common Variable Immunodeficiency, SARS CoV 2 Infection, Primary Antibody Deficiencies, COVID-19, Secondary Hypogammaglobulinemia