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

• ClinicalTrials.gov Identifier: NCT04852276
• Recruitment Status: Recruiting
• First Posted: April 21, 2021
• Last Update Posted: January 9, 2023
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Information provided by (Responsible Party): National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )

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
Immunodeficiencies; Immune Dysregulations

Detailed 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 prevaccination 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
• Estimated 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: April 20, 2021
• Estimated Primary Completion Date: June 30, 2025
• Estimated Study Completion Date: June 30, 2025

Groups and Cohorts

Group/Cohort
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 :

1. Change in S and RBD immunoglobulin G (IgG) antibody titer from baseline depending on vaccine manufacturer and platform [ Time Frame: 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 :

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

Eligibility Criteria

• Ages Eligible for Study: 3 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes
• Sampling Method: Non-Probability Sample

Study Population

Immunodeficient individuals will be recruited from NIAID protocols that evaluate primary or secondary immune deficiencies. Potential subjects will be identified by discussion between the study teams and review of medical and research records if necessary. They may also be referred from community practitioners who see this population.Healthy adult volunteers will be recruited through the NIH Clinical Research Volunteer Program, the Office of Patient Recruitment, MMG Patient Recruitment, ResearchMatch, or BuildClinical. Volunteers will also be recruited from existing NIH protocols. Healthy relatives of immunodeficient participants can be recruited for participation as controls if they meet enrollment criteria.

Criteria

• 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.

Contacts and Locations

Contacts

Contact: Emily E Ricotta, Ph.D.; (301) 761-7784; NIAIDCovidVaccineStudy@niaid.nih.gov

Locations

United States, Maryland

National Institutes of Health Clinical Center; Recruiting

Bethesda, Maryland, United States, 20892

Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR) 800-411-1222 ext TTY8664111010 prpl@cc.nih.gov

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

• Principal Investigator: Emily E Ricotta, Ph.D.; National Institute of Allergy and Infectious Diseases (NIAID)

More Information

Additional Information:

NIH Clinical Center Detailed Web Page 

Publications:

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.

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.

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.

• Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
• ClinicalTrials.gov Identifier: NCT04852276
• Other Study ID Numbers: 10000384; 000384-I
• First Posted: April 21, 2021
• Last Update Posted: January 9, 2023
• Last Verified: December 30, 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) ):

Adaptive immunity; clinical epidemiology; SARS-CoV-2; Coronavirus; Natural History

Additional relevant MeSH terms:

Immunologic Deficiency Syndromes; Immune System Diseases