Assessment of Immunogenicity of Zostavax® in Patients With Antibody Deficiency 60 Years of Age and Older
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Common variable immune deficiency (CVID), specific antibody deficiency (SAD), and X-linked agammaglobulinemia (XLA) are among the most common primary antibody deficiencies in which the mainstay of treatment is gammaglobulin replacement. The use of high doses of immunoglobulin replacement therapy and the early recognition of co-morbid diseases during the course of CVID, SAD, and XLA has improved survival and led to an aging population of CVID, SAD, and XLA patients.
The Advisory Committee on Immunization Practices (ACIP) recommends routine vaccination of all persons aged >60 years with 1 dose of vaccine directed against herpes zoster (Zostavax®) in the absence of any contraindications. Current standard of care includes avoidance of all vaccines when receiving gammaglobulin products due to passive immunity obtained from gammaglobulin against vaccine preventable infections. The exception to this rule is that patients on gammaglobulin should receive the yearly influenza vaccine due to its enhanced cell mediated immunity against the influenza virus. Clinical immunologists currently have no data upon which to advise patients receiving gammaglobulin replacement including those with CVID, SAD, and XLA concerning use of Zostavax®.
All gammaglobulin replacement products maintain protective antibody levels against VZV. However, humoral immune responses with anti-VZV antibodies are relatively constant and do not protect against the development of shingles. Varicella zoster virus specific cell mediated immunity (VZV-CMI), which is T cell dependent, is the critical component in preventing herpes zoster (shingles). VZV-CMI diminishes with age leaving the elderly most susceptible to shingles. Several studies have concluded that boosting VZV-CMI protects older adults from developing herpes zoster and postherpetic neuralgia (PHN).
Recommendations on the prevention of herpes zoster published in the Morbidity and Mortality Weekly Report (MMWR) by the Centers for disease control (CDC) in May 2008 make the following statements:
Zoster vaccine should not be administered to persons with primary or acquired immunodeficiency including:
a. Persons with clinical or laboratory evidence of other unspecified cellular immunodeficiency.
- Persons with impaired humoral immunity (e.g., hypogammaglobulinemia or dysgammaglobulinemia) can/should receive zoster vaccine.
The investigators hypothesize that vaccination with Zostavax® in adults with CVID, SAD, and XLA who have evidence of normal cell mediated immunity with normal T cell quantities and function will have a boost in VZV-CMI thereby reducing susceptibility to shingles and PHN.
Successful completion of this study will provide clinical immunologists with data upon which to advise antibody deficient patients concerning the use of Zostavax®.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
-
Florida
-
Saint Petersburg, Florida, United States, 33701
- University of South Florida
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion/Exclusion Criteria for Antibody Deficient Patients
Inclusion Criteria
- Adults 60 years of age and older
- Diagnosis of common variable immunodeficiency (CVID), Specific Antibody Deficiency (SAD), or X-linked agammaglobulinemia (XLA)
- Receiving replacement gammaglobulin
- Willing and able to sign consent and follow study schedule
- History of varicella or long-term (greater than or equal to 30 years) residence in the USA
Exclusion Criteria
- Allergy to Zostavax® or any of its components (i.e gelatin, neomycin)
- Absolute CD3, CD4, or CD8 lymphopenia as determined by age specific reference ranges
- Poor T cell function as indicated by a < 30 % increase in T cell response to mitogens or antigens as compared to the age matched normal reference range (in CVID) subjects
- Evidence of acute systemic illness or infection at within four weeks of screening or enrollment
- Prior herpes zoster infection
- Previously received herpes zoster vaccination
- Malignancy including solid tumors, leukemia, or lymphoma
- Presence of autoimmune or other inflammatory disease
- Use of immunosuppressive or immunomodulatory medications including chronic corticosteroids. Treatment for >2weeks of daily steroids will be considered chronic use.
- History of bleeding or chronic skin disorders.
- Pregnant or breastfeeding females
- Immunizations within one month
- Persons with HIV or AIDS
- Subject unwilling to sign consent or adhere to study schedule
- Any condition that in the opinion of the investigator would interfere with the conduct of the study
- Subjects unlikely to adhere to protocol follow-up
Inclusion/Exclusion Criteria for Healthy Subjects
Inclusion Criteria
- Adults 60 years of age and older
- Willing and able to sign consent and follow study schedule
- History of varicella or long-term (greater than or equal to 30 years) residence in the USA
Exclusion Criteria
- Allergy to Zostavax® or any of its components (i.e gelatin, neomycin)
- Evidence of acute systemic illness or infection at within four weeks of screening or enrollment
- Prior herpes zoster infection
- Previously received herpes zoster vaccination
- Malignancy including solid tumors, leukemia, or lymphoma
- Presence of autoimmune or other inflammatory disease
- Use of immunosuppressive or immunomodulatory medications including chronic corticosteroids. Treatment for >2weeks of daily steroids will be considered chronic use.
- History of bleeding or chronic skin disorders.
- Pregnant or breastfeeding females
- Immunizations within one month
- Persons with HIV or AIDS
- Subject unwilling to sign consent or adhere to study schedule
- Any condition that in the opinion of the investigator would interfere with the conduct of the study
- Subjects unlikely to adhere to protocol follow-up
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Experimental: Antibody Deficient Patients
Zostavax® vaccine administered to antibody deficient patients 60 years of age and older.
|
Zostavax® immunization
|
|
Active Comparator: Healthy Subjects
Zostavax® vaccine administered per standard of care to healthy adults 60 years of age and older.
|
Zostavax® immunization
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Determine in vitro changes in T cell proliferation preceding and following vaccination with Zostavax® by measurement of lymphocyte proliferation in response to VZV antigen.
Time Frame: Day 0, Week 4, 3 months, 6 months
|
Determine in vitro lymphocyte proliferation as counts per minute after stimulation of cells with varicella zoster antigen at time points preceding and following vaccination with Zostavax.
Blood samples will be obtained prior to administering the Zostavax® vaccine and post-vaccination at 4 weeks, 3 months, and 6 months.
|
Day 0, Week 4, 3 months, 6 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Determine in vitro changes in T cell proliferation preceding and following vaccination with Zostavax® by measurement of IFNg production by T cells in response to VZV antigen.
Time Frame: Day 0, Week 4, 3 months, 6 months
|
Determine in vitro IFNg production as Units/ml after stimulation of cells with varicella zoster antigen at time points preceding and following vaccination with Zostavax.
Blood samples will be obtained prior to administering the Zostavax® vaccine and post-vaccination at 4 weeks, 3 months, and 6 months.
|
Day 0, Week 4, 3 months, 6 months
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Jennifer Leiding, MD, University of South Florida
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- Pro00023706
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.