Analysis of the Immune Response to COVID-19 Vaccination and Outcomes in Individuals With and Without Immune Deficiencies and Dysregulations

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID) (NIH)

Overall Status

Recruiting

CT.gov ID

NCT04852276

Collaborator

(none)

600

Enrollment

Location

50.3

Anticipated Duration (Months)

11.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Background:

The immune system defends the body against disease and infection. Immune deficiencies are

health conditions that decrease the strength of this response. Vaccines stimulate the immune system to create a defense against a specific type of germ. Researchers want to compare immune system responses to COVID-19 vaccines in people with and without immune deficiencies.

Objective:

To learn about how people with immune deficiencies respond to COVID-19 vaccines.

Eligibility:

People age 12 and older with an immune deficiency who plan to get a COVID-19 vaccine. Healthy volunteers are also needed.

Design:

Participants will be screened with a medical record review.

Participants will give a blood sample before they get their first COVID-19 vaccine. Blood will be drawn from an arm vein using a needle. Blood can be drawn at the NIH, at a local doctor s office, or at a laboratory. It may also be drawn through a fingerstick at home. Participants will also complete 2 online surveys about their health and COVID-19 history.

Participants will give a second blood sample 2 to 4 weeks after they get the vaccine. They will complete 2 surveys about changes in their health and side effects from the vaccine.

If participants get a second (booster) vaccine, they will repeat the blood draw and surveys 3 to 4 weeks later.

Participants may give 3 optional blood samples in the 24 months after their last vaccine. They may also give saliva samples every 2 weeks while they are in the study.

Participation will last from 1 month to 2 years after the participant s last vaccine.

Condition or Disease	Intervention/Treatment	Phase
Immunodeficiencies Immune Dysregulations

Detailed Description

Study Description:

This prospective cohort study will assess the pre- and postvaccination immune responses in individuals with select immunodeficiencies and immune dysregulations compared to healthy volunteers who receive a coronavirus disease 2019 (COVID-19) vaccine, as well as any adverse events (AEs) experienced after vaccination. All required study visits for this

protocol may be conducted remotely; in-person visits at the NIH are optional. Subjects who have not yet been vaccinated will undergo baseline blood sampling using finger stick microsampler kits and/or venous blood draw within 7 days prior to receiving the vaccine. Additional samples will be collected approximately 21 days after dose 1 and approximately 28 days after dose 2 (if applicable). Optional samples may be collected at 6, 12, and 24 months post-vaccination. If subsequent booster doses are received while a participant is still on study, blood will again be drawn approximately 28 days after each booster dose, and then participants may proceed with the optional 6-, 12-, and 24-month follow-up sample collection. Participants who are able to attend in-person visits at NIH will have optional on-site blood draws 1 and 3 days after doses 1 and 2 (as applicable). Research evaluations will include baseline severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) antibody titers to the spike (S), nucleocapsid (N), and receptor binding domain (RBD) proteins, to assess pre-vaccination SARS-CoV-2 exposure and evaluate responses to vaccination. Additional immune markers of interest may include presence of autoantibodies, transcriptomic profiling, T-cell receptor (TCR) repertoire, among others. Participants who only submit finger stick home microsampler kits at the timepoints listed above will be evaluated for SARS-CoV-2 antibody titers and autoantibodies only. All subjects will be asked at baseline about prior COVID-19 diagnosis, symptoms, and severity, and will be asked additional questions at follow-up timepoints (including after additional booster doses) about vaccine AEs using standardized questionnaires.

Primary Objective:

To characterize the immune response to COVID-19 vaccination among immunodeficient and immune dysregulated individuals compared to healthy volunteers.

Secondary Objectives:

To characterize the COVID-19 vaccine-associated AEs among immunodeficient and immune dysregulated individuals compared to healthy volunteers.

Exploratory Objectives:

Assess the relationship between prior SARS-CoV-2 infection and vaccine-induced immune response.
To characterize pre-vaccine COVID-19 disease prevalence and severity among immunodeficient and immune dysregulated individuals.
To assess induction, strength, and durability of T- and B-cellspecific immune responses to SARS-CoV-2 (as measured by frequency and diversity of SARS-CoV-2 specific T and B cell clonotypes and titers of specific antibody responses), and their correlation to the underlying immune deficiency/dysregulation.
To characterize auto-antibodies present in immunodeficient and immune dysregulated individuals before and after COVID-19 vaccination.
To assess the incidence of post-vaccination breakthrough SARS-CoV-2 infection and to determine the SARS-CoV-2 virus genomic sequence in such cases.

Primary Endpoint:

Change in S and RBD immunoglobulin G (IgG) antibody titer from baseline to 14-21 days or 21-28 days (depending on vaccine manufacturer and platform) after vaccine dose 1, and 21-28 days after dose 2 and any subsequent doses (depending on vaccine manufacturer and platform).

Secondary Endpoints:

Incidence of vaccine-associated AEs experienced by immunodeficient individuals compared to healthy volunteers.

Exploratory Endpoints:

Characterization of post-vaccine immune response and AEs in patients with antibody evidence of prior SARS-CoV-2 infection
Pre- and post-vaccination incidence of COVID-19-associated symptoms experienced in individuals with immune deficiency/dysregulation who are positive for SARS-CoV-2 by serology or diagnostic polymerase chain reaction (PCR).
Characterize how various forms of immune deficiency or dysregulation impact generation, strength, and durability of T- and B-cell responses.
Incidence of autoantibodies pre- and post-COVID-19 vaccination comparing individuals with immune deficiency/dysregulation to healthy volunteers.

Study Design

Study Type:

Observational

Anticipated Enrollment :

600 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Analysis of the Immune Response to COVID-19 Vaccination and Outcomes in Individuals With and Without Immune Deficiencies and Dysregulations

Actual Study Start Date :

Apr 20, 2021

Anticipated Primary Completion Date :

Jun 30, 2025

Anticipated Study Completion Date :

Jun 30, 2025

Arms and Interventions

Arm	Intervention/Treatment
Control particpants Control participants will be healthy volunteers, and may include unaffected relatives of immunodeficient/dysregulated participants
Patients with immunodeficiencies and immune dysregulations Affected patients with evidence of a primary or secondary immune deficiency or dysregulation

Outcome Measures

Primary Outcome Measures

Change in S and RBD immunoglobulin G (IgG) antibody titer from baseline depending on vaccine manufacturer and platform [14-21 days or 21-28 days, depending on vaccine manufacturer and platform]
To characterize the immune response to COVID-19 vaccination among immunodeficient and immune dysregulated individuals compared to healthy volunteers

Secondary Outcome Measures

Incidence of vaccine-associated AEadverse events experienced by immunodeficient individuals compared to healthy volunteers [Throughout study]
To characterize the COVID-19 vaccine-associated adverse events among immunodeficient and immune dysregulated individuals compared to healthy volunteers

Eligibility Criteria

Criteria

Ages Eligible for Study:

3 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

INCLUSION CRITERIA:

In order to be eligible to participate in this study, an individual must meet the following criteria:

Aged 3 years and older.
Must be eligible to receive (based on official FDA authorization or approval) and scheduled to receive or have already received a COVID-19 vaccine outside of this facility.
Must meet the definition of affected participant or control participant:
Affected participants must have evidence of a primary or secondary immune deficiency or dysregulation under another NIAID protocol or as documented by an outside physician.
Control participants are healthy volunteers that do not have evidence of a primary or secondary immune deficiency or dysregulation and may include unaffected relatives of affected participants.
Ability to provide informed consent.
Willing to have blood samples stored for future research.
Able to proficiently speak, read, and write English.

EXCLUSION CRITERIA:

Individuals meeting any of the following criteria will be excluded from study participation:

Receipt of any other vaccine within 14 days prior to screening.
Planned non-COVID-19 vaccination within 28 days after COVID-19 vaccination(s).
Any condition that, in the opinion of the investigator, contraindicates participation in this study (e.g. specific autoinflammatory diseases, interferonopathies).
Self-reported history of HIV.