Multiple SclerosisNCT05286242
Evaluating the Immune Response to COVID19 Vaccination in Immunodeficient Patients
An observational study of Multiple Sclerosis and Autoimmune Blistering Disease, run by Yale University at 1 site in United States.
Trial summary
The purpose of this study is to understand the immune response to coronavirus disease-19 (COVID-19) vaccination in patients on B-cell depleting therapies (BCDT) over time, which in the future may help to inform clinical decision making in this patient population. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Multiple Sclerosis, Autoimmune Blistering Disease, B-Cell Deficiency
- What is being tested?
- COVID19 vaccine
- Type of treatment
- Vaccines
- How many people
- 196 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Feb 2021to 22 May 2026
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: There will be four groups of participants overall: * Patients with autoimmune neurologic/autoimmune blistering disease (AIBD) who are on B-cell depleting therapy (anti-CD20 monoclonal antibodies) * Patients with autoimmune neurologic/AIBD who are on other types of immunomodulators * Patients with autoimmune neurologic/AIBD who are untreated * Healthy controls
Who may be able to join
None listed.
Who cannot join
- Use of high dose steroids for treatment of neurologic/immunologic disease within 1 month of COVID-19 vaccination
- Anti-CD20 B-cell depleting therapy infused within 2 weeks of first study visit
- Inability to comply with the requirements of the protocol, in the opinion of the primary investigator
Trial locations and contacts
1 site in 1 country.
About this study
The purpose of this study is to understand the immune response to coronavirus disease-19 (COVID-19) vaccination in patients on B-cell depleting therapies (BCDT) over time, which in the future may help to inform clinical decision making in this patient population.
Read the detailed description
This will be a prospective, observational cohort study consisting of individuals with autoimmune diseases who are undergoing treatment with anti-CD20 medications at the time they receive a vaccine against COVID-19. Control groups will include healthy individuals, individuals with autoimmune diseases on other immunomodulators, and individuals with autoimmune diseases not on immunotherapy.
Participants will undergo serial blood draws and saliva collections at prespecified time points surrounding vaccination. A subset of agreeable participants will undergo skin biopsy within days of the first vaccination, with the option to repeat skin biopsy after the second vaccination. Additional blood, saliva and skin biopsy specimens may be obtained after booster vaccinations or after known COVID19 infections .
Specimens collected will be used for studies aimed at (1) understanding the pathobiology of neurologic/inflammatory/immune diseases and the immunologic response to COVID-19 vaccination, (2) identifying how and why treatments used for neurologic/immune diseases may impact the effectiveness of vaccination, and (3) identifying dermatologic manifestations of the immunologic response to the COVID-19 mRNA vaccine.
The investigators are investigating both the production of antibodies against the virus over time and deeply interrogating the T-cell response to vaccination using methods that measure T-cell reactivity to the COVID-19 virus, including single cell RNA sequencing.
- Being tested
- COVID19 vaccine
- Medical subject headings
- Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
COVID19 vaccineBiological
All participants receive one or more FDA-authorized COVID19 vaccinations according to standard of care and current medical recommendations. The intervention is not specifically administered as part of the study.
| Study group | Role | What they receive |
|---|---|---|
| Healthy control | Healthy controls Participants will receive COVID19 vaccination according to standard of care (any FDA approved vaccine). They will donate serial biospecimens before and after vaccination according to the study design. Receives: Biological: COVID19 vaccine | |
| Disease control | Disease controls (individuals with a qualifying autoimmune condition, but not treated with any immunomodulator).
Participants will receive COVID19 vaccination according to standard of care (any FDA approved vaccine). They will donate serial biospecimens before and after vaccination according to the study design. Receives: Biological: COVID19 vaccine | |
| B-cell depleted | Individuals with autoimmune disease (multiple sclerosis or autoimmune blistering disease) who are treated with B-cell depleting anti-CD20 monoclonal antibodies.
Participants will receive COVID19 vaccination according to standard of care (any FDA approved vaccine). They will donate serial biospecimens before and after vaccination according to the study design. Receives: Biological: COVID19 vaccine | |
| Other immunomodulator | Individuals with autoimmune disease (multiple sclerosis or autoimmune blistering disease) who are treated with a non-CD20 monoclonal antibody immunomodulator to treat their disease.
Participants will receive COVID19 vaccination according to standard of care (any FDA approved vaccine). They will donate serial biospecimens before and after vaccination according to the study design. Receives: Biological: COVID19 vaccine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in coronavirus disease 19 (COVID19) antibody titers over time
COVID 19 spike and neutralizing antibody titers will be monitored serially
Measured: Baseline, 2 weeks post vaccine 1, pre-vaccine 2, 1 week post vaccine 2, 6 months post vaccine 2; pre- and 2 week post any additional vaccines
Change in severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) specific T-cell activation over time
Flow cytometry characterizing immunophenotype of SARS-CoV2 specific T cells
Measured: Baseline, 2 weeks post vaccine 1, pre-vaccine 2, 1 week post vaccine 2, 6 months post vaccine 2; pre- and 2 week post any additional vaccines
Secondary outcomes (6)
Skin biopsy analysis
Histologic and immunologic characterization of skin biopsy specimens, comparing vaccinated to unvaccinated arm, at one or more timepoints post-vaccination
Measured: 7 days post vaccine 1; 7 days post vaccine 2; 4 days post booster (all timepoints optional)
Measurement of COVID19 antibodies in saliva
Descriptive assessment of whether COVID antibodies can be detected in saliva at any time point
Measured: Baseline, 2 weeks post vaccine 1, pre-vaccine 2, 1 week post vaccine 2, 6 months post vaccine 2; pre- and 2 week post any additional vaccines
Immune analysis
Deep immunologic assessment (flow cytometry, single cell RNA sequencing) of blood specimens; descriptive analysis at each timepoint with comparisons over time will be performed.
Measured: Baseline, 2 weeks post vaccine 1, pre-vaccine 2, 1 week post vaccine 2, 6 months post vaccine 2; pre- and 2 week post any additional vaccines
Changes in patient reported outcomes: COVID history
Subjective reports of vaccination-associated symptoms and COVID risk factors (COVID-19 survey)
Measured: Baseline, 2 weeks post vaccine 1, pre-vaccine 2, 1 week post vaccine 2, 6 months post vaccine 2; pre- and 2 week post any additional vaccines
Change in patient reported outcomes: patient reported disability steps
Subjects will complete Patient Derived Disability Step score
Measured: Baseline, 2 weeks post vaccine 1, pre-vaccine 2, 1 week post vaccine 2, 6 months post vaccine 2; pre- and 2 week post any additional vaccines
Change in patient reported outcomes: overall symptoms
SymptoMS screening questionnaire
Measured: Baseline, 2 weeks post vaccine 1, pre-vaccine 2, 1 week post vaccine 2, 6 months post vaccine 2; pre- and 2 week post any additional vaccines
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Mar 2022
- Study start10 Feb 2021
- Primary completion22 May 2026
- Study completion22 May 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 196 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID), Robert Leet and Clara Guthrie Patterson Trust
- Responsible party
- Sponsor
- Investigators
- Erin Longbrake, Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05286242
- Sponsor's protocol ID
- 2000029889
- Other IDs
- 2U19AI089992-11, 2U19AI089992-06A1
- Status last verified
- May 2026
- First submitted
- 15 Mar 2022
- Last updated
- 28 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Sequencing data will be made publicly available upon publication of the study. Other study related data will be made available upon request and presentation of an appropriate research plan by qualified researchers
Study at a glance
From the registry record, last updated by the sponsor on 28 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluating the Immune Response to COVID19 Vaccination in Immunodeficient Patients
- ClinicalTrials.gov ID
- NCT05286242
- Acronym / sponsor ID
- 2000029889
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 196 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID), Robert Leet and Clara Guthrie Patterson Trust
- Study start
- 10 Feb 2021 (actual)
- Primary completion
- 22 May 2026 (actual)
- Study completion
- 22 May 2026 (actual)
- First posted
- 18 Mar 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to understand the immune response to coronavirus disease-19 (COVID-19) vaccination in patients on B-cell depleting therapies (BCDT) over time, which in the future may help to inform clinical decision making in this patient population.
Detailed description
This will be a prospective, observational cohort study consisting of individuals with autoimmune diseases who are undergoing treatment with anti-CD20 medications at the time they receive a vaccine against COVID-19. Control groups will include healthy individuals, individuals with autoimmune diseases on other immunomodulators, and individuals with autoimmune diseases not on immunotherapy.
Participants will undergo serial blood draws and saliva collections at prespecified time points surrounding vaccination. A subset of agreeable participants will undergo skin biopsy within days of the first vaccination, with the option to repeat skin biopsy after the second vaccination. Additional blood, saliva and skin biopsy specimens may be obtained after booster vaccinations or after known COVID19 infections .
Specimens collected will be used for studies aimed at (1) understanding the pathobiology of neurologic/inflammatory/immune diseases and the immunologic response to COVID-19 vaccination, (2) identifying how and why treatments used for neurologic/immune diseases may impact the effectiveness of vaccination, and (3) identifying dermatologic manifestations of the immunologic response to the COVID-19 mRNA vaccine.
The investigators are investigating both the production of antibodies against the virus over time and deeply interrogating the T-cell response to vaccination using methods that measure T-cell reactivity to the COVID-19 virus, including single cell RNA sequencing.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Healthy control | – | Biological: COVID19 vaccineHealthy controls Participants will receive COVID19 vaccination according to standard of care (any FDA approved vaccine). They will donate serial biospecimens before and after vaccination according to the study design. |
| Disease control | – | Biological: COVID19 vaccineDisease controls (individuals with a qualifying autoimmune condition, but not treated with any immunomodulator). Participants will receive COVID19 vaccination according to standard of care (any FDA approved vaccine). They will donate serial biospecimens before and after vaccination according to the study design. |
| B-cell depleted | – | Biological: COVID19 vaccineIndividuals with autoimmune disease (multiple sclerosis or autoimmune blistering disease) who are treated with B-cell depleting anti-CD20 monoclonal antibodies. Participants will receive COVID19 vaccination according to standard of care (any FDA approved vaccine). They will donate serial biospecimens before and after vaccination according to the study design. |
| Other immunomodulator | – | Biological: COVID19 vaccineIndividuals with autoimmune disease (multiple sclerosis or autoimmune blistering disease) who are treated with a non-CD20 monoclonal antibody immunomodulator to treat their disease. Participants will receive COVID19 vaccination according to standard of care (any FDA approved vaccine). They will donate serial biospecimens before and after vaccination according to the study design. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- There will be four groups of participants overall: * Patients with autoimmune neurologic/autoimmune blistering disease (AIBD) who are on B-cell depleting therapy (anti-CD20 monoclonal antibodies) * Patients with autoimmune neurologic/AIBD who are on other types of immunomodulators * Patients with autoimmune neurologic/AIBD who are untreated * Healthy controls
Key inclusion criteria (0 listed)
Key exclusion criteria (3 listed)
- Use of high dose steroids for treatment of neurologic/immunologic disease within 1 month of COVID-19 vaccination
- Anti-CD20 B-cell depleting therapy infused within 2 weeks of first study visit
- Inability to comply with the requirements of the protocol, in the opinion of the primary investigator
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| COVID19 vaccineAll participants receive one or more FDA-authorized COVID19 vaccinations according to standard of care and current medical recommendations. The intervention is not specifically administered as part of the study. | Biological | B-cell depleted, Disease control, Healthy control, Other immunomodulator |
Primary outcome
Change in coronavirus disease 19 (COVID19) antibody titers over time
Time frame: Baseline, 2 weeks post vaccine 1, pre-vaccine 2, 1 week post vaccine 2, 6 months post vaccine 2; pre- and 2 week post any additional vaccines
COVID 19 spike and neutralizing antibody titers will be monitored serially
Change in severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) specific T-cell activation over time
Time frame: Baseline, 2 weeks post vaccine 1, pre-vaccine 2, 1 week post vaccine 2, 6 months post vaccine 2; pre- and 2 week post any additional vaccines
Flow cytometry characterizing immunophenotype of SARS-CoV2 specific T cells
6 secondary outcomes
Skin biopsy analysis
Time frame: 7 days post vaccine 1; 7 days post vaccine 2; 4 days post booster (all timepoints optional)
Measurement of COVID19 antibodies in saliva
Time frame: Baseline, 2 weeks post vaccine 1, pre-vaccine 2, 1 week post vaccine 2, 6 months post vaccine 2; pre- and 2 week post any additional vaccines
Immune analysis
Time frame: Baseline, 2 weeks post vaccine 1, pre-vaccine 2, 1 week post vaccine 2, 6 months post vaccine 2; pre- and 2 week post any additional vaccines
Changes in patient reported outcomes: COVID history
Time frame: Baseline, 2 weeks post vaccine 1, pre-vaccine 2, 1 week post vaccine 2, 6 months post vaccine 2; pre- and 2 week post any additional vaccines
Change in patient reported outcomes: patient reported disability steps
Time frame: Baseline, 2 weeks post vaccine 1, pre-vaccine 2, 1 week post vaccine 2, 6 months post vaccine 2; pre- and 2 week post any additional vaccines
Change in patient reported outcomes: overall symptoms
Time frame: Baseline, 2 weeks post vaccine 1, pre-vaccine 2, 1 week post vaccine 2, 6 months post vaccine 2; pre- and 2 week post any additional vaccines
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 May 2026.
- Individual participant dataSharing planned: Undecided. Sequencing data will be made publicly available upon publication of the study. Other study related data will be made available upon request and presentation of an appropriate research plan by qualified researchers
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Erin Longbrake principal investigator
Yale University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Multiple Sclerosis and Autoimmune Blistering Disease, run by Yale University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 0 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in coronavirus disease 19 (COVID19) antibody titers over time (time frame: Baseline, 2 weeks post vaccine 1, pre-vaccine 2, 1 week post vaccine 2, 6 months post vaccine 2; pre- and 2 week post any additional vaccines). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 May 2026.