Herpes Zoster
Conditions
Keywords
Herpes zoster, immune response, Zostavax, twins, non-twins
Brief summary
In this study the investigators are trying to identify immune signatures that are associated with effective or poor vaccine responses to naturally-acquired herpes zoster virus and the zoster (shingles) vaccine, Zostavax.
Detailed description
This study will examine the frequency, phenotype and repertoire of VZV-specific T cells. The frequency and T-Cell Receptor (TCR) diversity of VZV-specific T cells on days 7 and 14 after vaccination will be examined. The titer of anti-VZV antibodies and T cell frequencies will be examined on day 28 post vaccination.
Interventions
BIOLOGICALZostavax™
In the Vaccination arm, healthy individuals will be vaccinated with the licensed zoster vaccine, Zostavax.
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Stanford University
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Otherwise healthy adult non-twins and twin pairs, 40-49 years of age (Cross-Sectional study) or 50 years of age and older (Vaccination study). If a volunteer cannot participate in the Vaccination study after screening, may be considered for Cross-Sectional study. * History of prior chicken pox infection or living within the continental U.S. for past 30 years * Willing to complete the informed consent process * Availability for follow-up for the planned duration of the study (Cross-Sectional study: 1 visit; Vaccination study: 5 visits within 4-5 weeks) * Acceptable medical history and vital signs
Exclusion criteria
* History of shingles within 5 years of enrollment * Prior vaccination with Zostavax vaccine for prevention of shingles * Vaccination Study only: History of severe allergic reactions to vaccine components, including gelatin and neomycin. * Vaccination Study only: Life-threatening reactions to previous vaccinations. * Vaccination Study only: Adults weighing less than 110 pounds. * Active systemic or serious concurrent illness, including febrile illness on the day of enrollment/vaccination * History of immunodeficiency disorder * Chronic HIV, Hepatitis B or Hepatitis C infection * Known or suspected impairment of immunologic function, including, but not limited to clinically significant liver disease, diabetes mellitus treated with insulin, moderate to severe renal disease or any other chronic disorder which, in the opinion of the investigator, might jeopardize volunteer safety or compliance with the protocol. * Recent or current use of immunosuppressive medication, or anticipated use during study period, including systemic corticosteroids (corticosteroid nasal sprays, inhaled steroids and topical steroids are permissible). * Blood pressure \>150 systolic or \> 95 diastolic at Visit 1 * History of chemotherapy treatment for cancer. * Malignancy, other than squamous cell or basal cell skin cancer (includes solid tumors such as breast cancer with recurrence in the past year and any hematologic cancer such as leukemia or lymphoma) which, in the opinion of the investigator, might jeopardize volunteer safety or compliance with the protocol. Prostate cancer may be acceptable if no metastases and not undergoing treatment with immunosuppressive medications. * Autoimmune disease, including rheumatoid arthritis, treated with immunosuppressive medication such as Plaquenil, methotrexate, prednisone, Enbrel, which in the opinion of the investigator, might jeopardize volunteer safety or compliance with the protocol (thyroid disease may be acceptable). * History of blood dyscrasias, renal disease, or hemoglobinopathies requiring regular medical follow up or hospitalization during the preceding year * Use of anti-coagulation medication such as Coumadin or Lovenox, or anti-platelet agents such as aspirin (except aspirin up to 325 mg. daily), Plavix or Aggrenox which may, in the opinion of the investigator, jeopardize volunteer safety or compliance with the protocol. * Receipt of blood or blood products within 6 months prior to enrollment and during the study period * Use of antiviral medications within 24 hrs. prior to enrollment, and for the Vaccination study, for the 14 days following study vaccination. * Inactivated vaccine within 14 days prior to enrollment and during study period(avoid non-study related immunization during the study period) * Live, attenuated vaccine within 60 days prior to enrollment and during study period (avoid non-study related immunization during the study period) * Pregnant or lactating woman, planning to become pregnant (pregnancy should be avoided for 3 months following administration of Zostavax vaccine). * Use of investigational agents within 30 days prior to enrollment and during study period * Donation of a unit of blood within 6 weeks prior to enrollment and during study period * Medical or psychiatric condition or occupational responsibilities that preclude subject compliance with the protocol * Any condition which, in the opinion of the investigator, might interfere with volunteer safety, study objectives or the ability of the participant to understand or comply with the study protocol.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants Who Received Zostavax Immunization or Had Natural Exposure to VZV | Day 0 to Day 35 |
Secondary
| Measure | Time frame |
|---|---|
| Number of Participants With Related Adverse Events | 0 to 35 Days |
Other
| Measure | Time frame | Description |
|---|---|---|
| Identify Predictors That Correlate With a Rapid and Diverse T Cell Response. | 0 to 14 Days | The investigators will use the frequency and TCR diversity of VZV-specific T cells on days 7 and 14 after vaccination as outcome variable and identify predictors that positively or negatively correlate with a rapid and diverse T cell response in the different age groups. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Zostavax™ Vaccine Group Participants \> 50 years received a single dose 0.65 ml Zostavax™ (live, attenuated zoster vaccine) administered by subcutaneous injection. | 45 |
| Naturally-acquired VZV Immunity Participants 40-49 years of age did not receive any intervention with the objective of examining the influence of age and inherited factors on the varicella zoster virus (VZV)-specific immune response in those with a naturally-acquired VZV immunity (a prior history of chicken pox). | 9 |
| Total | 54 |
Baseline characteristics
| Characteristic | Zostavax™ Vaccine Group | Naturally-acquired VZV Immunity | Total |
|---|---|---|---|
| Age, Customized Age 40-49 Years Old | 0 Participants | 9 Participants | 9 Participants |
| Age, Customized Age 50 and above | 45 Participants | 0 Participants | 45 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 0 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 40 Participants | 9 Participants | 49 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) White | 43 Participants | 7 Participants | 50 Participants |
| Region of Enrollment United States | 45 participants | 9 participants | 54 participants |
| Sex: Female, Male Female | 21 Participants | 7 Participants | 28 Participants |
| Sex: Female, Male Male | 24 Participants | 2 Participants | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 3 / 45 | 0 / 9 |
| serious Total, serious adverse events | 0 / 45 | 0 / 9 |
Outcome results
Primary
Number of Participants Who Received Zostavax Immunization or Had Natural Exposure to VZV
Time frame: Day 0 to Day 35
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Zostavax™ Vaccine Group | Number of Participants Who Received Zostavax Immunization or Had Natural Exposure to VZV | 45 Participants |
| Naturally-acquired VZV Immunity | Number of Participants Who Received Zostavax Immunization or Had Natural Exposure to VZV | 9 Participants |
Secondary
Number of Participants With Related Adverse Events
Time frame: 0 to 35 Days
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Zostavax™ Vaccine Group | Number of Participants With Related Adverse Events | Erythema at injection site greater 5 cm | 5 Participants |
| Zostavax™ Vaccine Group | Number of Participants With Related Adverse Events | No related AEs | 40 Participants |
| Naturally-acquired VZV Immunity | Number of Participants With Related Adverse Events | Erythema at injection site greater 5 cm | 0 Participants |
| Naturally-acquired VZV Immunity | Number of Participants With Related Adverse Events | No related AEs | 9 Participants |
Other Pre-specified
Identify Predictors That Correlate With a Rapid and Diverse T Cell Response.
The investigators will use the frequency and TCR diversity of VZV-specific T cells on days 7 and 14 after vaccination as outcome variable and identify predictors that positively or negatively correlate with a rapid and diverse T cell response in the different age groups.
Time frame: 0 to 14 Days