Clinical trial NCT05321407: COVID-19 Vaccine Responses in PIDD Subjects
Official title: Vaccine-induced SARS-CoV-2-specific T Cell Responses in Patients With Primary Immune Deficiency Disease
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: X-linked Agammaglobulinemia
XLA
Primary Immune Deficiency
CVID
Common Variable Immunodeficiency
Primary Antibody Deficiencies
Secondary Hypogammaglobulinemia
Keywords: X-linked Agammaglobulinemia
Primary Immune Deficiency
Common Variable Immunodeficiency
SARS CoV 2 Infection
Primary Antibody Deficiencies
COVID-19
Secondary Hypogammaglobulinemia
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: Jeffrey Modell Foundation
name: University of North Carolina, Chapel Hill
name: University of South Florida
name: National Institute of Allergy and Infectious Diseases (NIAID)
First posted: 2022-04-11
Enrollment: 100
Sex: ALL
Minimum age (years): 6
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
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.

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

1. Diagnosis of antibody deficiency with confirmatory lab or genetic testing
2. Stable on immunoglobulin replacement therapy
3. Age \>6 months 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

Primary outcomes:
measure: Spike (S) protein-specific T cell responses to stimulation with SARS-CoV-2 wild-type peptides (measured as a percentage of total T cells).
timeFrame: 2 years
measure: Spike (S) protein-specific T cell responses to stimulation with SARS-CoV-2 alpha variant peptides (measured as a percentage of total T cells).
timeFrame: 2 years
measure: Spike (S) protein-specific T cell responses to stimulation with SARS-CoV-2 beta variant peptides (measured as a percentage of total T cells).
timeFrame: 2 years
measure: Spike (S) protein-specific T cell responses to stimulation with SARS-CoV-2 delta variant peptides (measured as a percentage of total T cells).
timeFrame: 2 years
measure: Spike (S) protein-specific T cell responses to stimulation with SARS-CoV-2 omicron variant peptides (measured as a percentage of total T cells).
timeFrame: 2 years
Secondary outcomes:
measure: S-specific T cell responses (as a percentage of total T cells) to SARS-CoV-2 vaccination in primary antibody deficiency over time.
timeFrame: 2 years
measure: S-specific T cell responses (as a percentage of total T cells) to SARS-CoV-2 vaccination in secondary antibody deficiency over time.
timeFrame: 2 years
measure: S-specific T cell responses (as a percentage of total T cells) to SARS-CoV-2 in infected participants.
timeFrame: 2 years
measure: S-specific T cell responses (as a percentage of total T cells) to SARS-CoV-2 in vaccinated participants.
timeFrame: 2 years
measure: Number of vaccinated participants who develop severe COVID-19 clinical outcomes.
timeFrame: 2 years
measure: Number of infected participants who develop severe COVID-19 clinical outcomes.
timeFrame: 2 years
measure: Number of antibody deficiency participants who develop severe COVID-19 clinical outcomes.
timeFrame: 2 years
Other outcomes:
Locations:
city: Saint Petersburg
country: United States
facility: University of South Florida
state: Florida
city: Chapel Hill
country: United States
facility: University of North Carolina, Chapel Hill
state: North Carolina
city: Durham
country: United States
facility: Duke University
state: North Carolina
Study officials:
affiliation: Duke University
name: John Sleasman, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of North Carolina, Chapel Hill
name: Kristina De Paris, PhD
role: PRINCIPAL_INVESTIGATOR
References: