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

Immunodeficiencies Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04852276
• Other study ID #: 10000384
• Secondary ID: 000384-I
• Status: Completed
• Start date: April 20, 2021
• Est. completion date: August 31, 2023

Study information

• Verified date: October 6, 2023
• Source: National Institutes of Health Clinical Center (CC)
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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 3 and older with an immune deficiency who plan to get a COVID-19 vaccine. Healthy volunteers are also needed.

Design:

Participants will be pre-screened for eligibility, including COVID-19 vaccination history and immune status.

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. Additional surveys are optional.

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 another COVID-19 vaccine dose, 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 for 6 months following their last vaccine.

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

Description:

Study Description:

This prospective cohort study will assess the pre- and post-vaccination 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 requested from participants approximately 14-21 days after dose 1 and 21-28 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 samples will again be requested approximately 28 days after each booster dose, through the 5th COVID-19 vaccine dose received, 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-cell specific 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 264
• Est. completion date: August 31, 2023
• Est. primary completion date: August 31, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 3 Years and older

Eligibility

• INCLUSION CRITERIA:

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

1. Aged 3 years and older.

2. 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.

3. Must meet the definition of affected participant or control participant:

1. 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.

2. 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.

4. Ability to provide informed consent.

5. Willing to have blood samples stored for future research.

6. Able to proficiently speak, read, and write English.

EXCLUSION CRITERIA:

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

1. Receipt of any other vaccine within 14 days prior to screening.

2. Planned non-COVID-19 vaccination within 28 days after COVID-19 vaccination(s).

3. Any condition that, in the opinion of the investigator, contraindicates participation in this study (e.g. specific autoinflammatory diseases, interferonopathies).

4. Self-reported history of HIV.

Related Conditions & MeSH terms

• Immunodeficiencies
• Immunologic Deficiency Syndromes

Locations

Country	Name	City	State
United States	National Institutes of Health Clinical Center	Bethesda	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)

Country where clinical trial is conducted

United States, 

References & Publications (3)

Bonilla FA. Vaccines in Patients with Primary Immune Deficiency. Immunol Allergy Clin North Am. 2020 Aug;40(3):421-435. doi: 10.1016/j.iac.2020.03.004. — View Citation

Jackson LA, Anderson EJ, Rouphael NG, Roberts PC, Makhene M, Coler RN, McCullough MP, Chappell JD, Denison MR, Stevens LJ, Pruijssers AJ, McDermott A, Flach B, Doria-Rose NA, Corbett KS, Morabito KM, O'Dell S, Schmidt SD, Swanson PA 2nd, Padilla M, Mascola JR, Neuzil KM, Bennett H, Sun W, Peters E, Makowski M, Albert J, Cross K, Buchanan W, Pikaart-Tautges R, Ledgerwood JE, Graham BS, Beigel JH; mRNA-1273 Study Group. An mRNA Vaccine against SARS-CoV-2 - Preliminary Report. N Engl J Med. 2020 Nov 12;383(20):1920-1931. doi: 10.1056/NEJMoa2022483. Epub 2020 Jul 14. — View Citation

Szczawinska-Poplonyk A, Breborowicz A, Samara H, Ossowska L, Dworacki G. Impaired Antigen-Specific Immune Response to Vaccines in Children with Antibody Production Defects. Clin Vaccine Immunol. 2015 Aug;22(8):875-82. doi: 10.1128/CVI.00148-15. Epub 2015 May 27. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in S and RBD immunoglobulin G (IgG) antibody titer from baseline 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	14-21 days or 21-28 days, depending on vaccine manufacturer and platform
Secondary	Incidence of vaccine-associated adverse events (AE) experienced by immunodeficient individuals compared to healthy volunteers	To characterize the COVID-19 vaccine-associated adverse events among immunodeficient and immune dysregulated individuals compared to healthy volunteers	Throughout study

External Links

•   NIH Clinical Center Detailed Web Page