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

Overview

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.

Study Type

  • Study Type: Observational
  • Study Design
    • Time Perspective: Prospective
  • Study Primary Completion Date: June 30, 2025

Detailed Description

The novel human severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes coronavirus disease (COVID-19). This acute respiratory syndrome is associated with activation of the innate immune system and a hyper-inflammatory response which can lead to life-threatening symptoms. There are a number of primary immunodeficiencies (PIDs) that prevent complete activation of innate immune cells or other pro-inflammatory mediators, as well as secondary immune deficiencies that evoke the same dysfunctional immune response. Because the extent to which these individuals experience COVID-19 is unknown, vaccination against SARS-CoV-2 is critical. In December 2020, the FDA announced Emergency Use Authorization for two mRNA-based SARS-CoV-2 vaccines. While evaluation of the immune response to these vaccines in healthy volunteers is ongoing, no large-scale characterization of the immune response in immunodeficient individuals has been undertaken. This prospective cohort study will assess and describe the baseline and post-vaccination immune response in individuals with select immune deficiencies compared to healthy volunteers who receive a COVID-19 vaccine, as well as any adverse events (AEs) experienced after either dose. 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 the booster dose. For individuals who are enrolled but have not yet had samples collected, a sample will be drawn prior to the booster. 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 about vaccine AEs using standardized questionnaires. The goal of this protocol is to gain a comprehensive understanding of the variety of immune responses in immunodeficient individuals.

Arms, Groups and Cohorts

  • 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

Clinical Trial Outcome Measures

Primary Measures

  • 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 Measures

  • 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

Participating in This Clinical Trial

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.

Gender Eligibility: All

Minimum Age: 3 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

Investigator Details

  • Lead Sponsor
    • National Institute of Allergy and Infectious Diseases (NIAID)
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Emily E Ricotta, Ph.D., Principal Investigator, National Institute of Allergy and Infectious Diseases (NIAID)
  • Overall Contact(s)
    • Emily E Ricotta, Ph.D., (301) 761-7784, NIAIDCovidVaccineStudy@niaid.nih.gov

References

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. Review.

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.

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