Assessment of Immunogenicity of Zostavax® in Patients With Antibody Deficiency 60 Years of Age and Older

Brief Title

Assessment of Immunogenicity of Zostavax® in Patients With Antibody Deficiency 60 Years of Age and Older

Official Title

Assessment of Immunogenicity of Zostavax® in Patients With Antibody Deficiency 60 Years of Age and Older

Brief Summary

      Recommendations concerning the administration of Zostavax® in patients with antibody
      deficiency are unclear. The investigators plan to assess the immunogenicity and safety of
      Zostavax® in patients with antibody deficiency as compared with healthy volunteers.
    

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:

        1. 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.

        2. 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

Interventional


Primary Outcome

Determine in vitro changes in T cell proliferation preceding and following vaccination with Zostavax® by measurement of lymphocyte proliferation in response to VZV antigen.

Secondary Outcome

 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.

Condition

Common Variable Immune Deficiency

Intervention

Zostavax®

Study Arms / Comparison Groups

 Antibody Deficient Patients
Description:  Zostavax® vaccine administered to antibody deficient patients 60 years of age and older.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Biological

Estimated Enrollment

2

Start Date

December 2015

Completion Date

December 2017

Primary Completion Date

December 2017

Eligibility Criteria

        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
      

Gender

All

Ages

60 Years - N/A

Accepts Healthy Volunteers

Accepts Healthy Volunteers

Contacts

Jennifer Leiding, MD, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT02960399

Organization ID

Pro00023706


Responsible Party

Sponsor

Study Sponsor

University of South Florida

Collaborators

 Merck Sharp & Dohme Corp.

Study Sponsor

Jennifer Leiding, MD, Principal Investigator, University of South Florida


Verification Date

April 2018