COVID-19 Vaccine Responses in PIDD Subjects

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

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.

Study Overview

• Status: Recruiting
• Conditions: Common Variable Immunodeficiency; X-linked Agammaglobulinemia; Primary Immune Deficiency; Primary Antibody Deficiencies; CVID; XLA; Secondary Hypogammaglobulinemia

Detailed Description

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.

• Study Type: Observational
• Enrollment (Anticipated): 100

Contacts and Locations

• Study Contact: Name: Guglielmo Venturi, PhD; Phone Number: 919-613-6818; Email: XLACOVIDvax@duke.edu

Study Locations

• United States
  • Florida
    • Saint Petersburg, Florida, United States, 33701
      • Recruiting
      • University of South Florida
      • Contact: Guglielmo Venturi, PhD; Email: XLACOVIDvax@duke.edu
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • Recruiting
      • University of North Carolina, Chapel Hill
      • Contact: Guglielmo Venturi, PhD; Email: XLACOVIDvax@duke.edu
    • Durham, North Carolina, United States, 27708
      • Recruiting
      • Duke University
      • Contact: Guglielmo Venturi, PhD; Email: XLACOVIDvax@duke.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Approximately 50 subjects with primary antibody deficiency diseases and 50 healthy controls will be enrolled through the Duke University Medical Center's Allergy and Immunology clinics for the Departments of Medicine and Pediatrics, in addition to collaboration with University of North Carolina, Chapel Hill and University of South Florida.

Description

Inclusion Criteria:

1. Diagnosis of antibody deficiency with confirmatory lab or genetic testing
2. Stable on immunoglobulin replacement therapy
3. Age >5 years and able to provide consent, or assent with parental consent if <18 years
4. 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

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
X-linked agammaglobulinemia (XLA); 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?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Duke University
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID); University of South Florida; University of North Carolina, Chapel Hill; Jeffrey Modell Foundation
• Investigators: Principal Investigator: John Sleasman, MD, Duke University; Principal Investigator: Kristina De Paris, PhD, University of North Carolina, Chapel Hill

Study record dates

Study Major Dates

• Study Start (Actual): September 24, 2021
• Primary Completion (Anticipated): December 31, 2024
• Study Completion (Anticipated): December 31, 2024

Study Registration Dates

• First Submitted: April 7, 2022
• First Submitted That Met QC Criteria: April 7, 2022
• First Posted (Actual): April 11, 2022

Study Record Updates

• Last Update Posted (Actual): May 19, 2023
• Last Update Submitted That Met QC Criteria: May 18, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Common Variable Immunodeficiency; COVID-19; Primary Immune Deficiency; SARS CoV 2 Infection; X-linked Agammaglobulinemia; Primary Antibody Deficiencies; Secondary Hypogammaglobulinemia
• Additional Relevant MeSH Terms: Immune System Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Hematologic Diseases; Genetic Diseases, Inborn; Blood Protein Disorders; Immunologic Deficiency Syndromes; Primary Immunodeficiency Diseases; Agammaglobulinemia; Common Variable Immunodeficiency
• Other Study ID Numbers: Pro00108422; R21AI168980 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No