Evaluating the Immune Response to COVID19 Vaccination in Immunodeficient Patients

Yale University

Status: Active, not recruiting

Conditions: Multiple Sclerosis; Autoimmune Blistering Disease; B-Cell Deficiency

Treatments: Biological: COVID19 vaccine

Study type: Observational

Funder types: Other; NIH

Identifiers

NCT05286242

2U19AI089992-06A1 (U.S. NIH Grant/Contract)

2000029889

2U19AI089992-11 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 400 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

Subjects with neurologic/immunologic condition:

• at least 18 years of age

• Known diagnosis of autoimmune neurologic disease (e.g. multiple sclerosis (MS), neuromyelitis optica, myelin oligodendrocyte glycoprotein (MOG) -associated disorder) or autoimmune blistering disease (AIBD).

• EITHER:

  • Treated with an anti-CD20 (rituximab, ocrelizumab) medications for >6 months at the time of vaccination (B-cell depletion therapy, BCDT)
  • On no immunomodulatory therapy for their autoimmune condition for >6 months at the time of vaccination
  • Treated with a non-BCDT immunotherapy

• No relapse of neurologic/immunologic disease for >6 months prior to the time of enrollment

• Subject is eligible and willing to receive COVID-19 vaccination in accordance with local and national guidelines, or subject intends to receive booster COVID-19 vaccination in accordance with recommendations from their primary medical team.

• No active skin condition (e.g. open sores) preventing blood draw

Healthy Controls:

• at least 18 years of age
• No evidence of neurological/immunologic disease/illness/condition
• Subject is eligible and willing to receive COVID-19 vaccination in accordance with local and national guidelines, or subject intends to receive booster COVID-19 vaccination in accordance with recommendations from their primary medical team.
• No active skin condition (e.g. open sores) preventing blood draw/skin biopsy

Exclusion Criteria:

• 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 design

400 participants in 4 patient groups

Healthy control

Description:

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.

Treatment:

Biological: COVID19 vaccine

Disease control

Description:

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.

Treatment:

Biological: COVID19 vaccine

B-cell depleted

Description:

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.

Treatment:

Biological: COVID19 vaccine

Other immunomodulator

Description:

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.

Treatment:

Biological: COVID19 vaccine