T Cell Responses to Varicella Zoster Virus (VZV) Vaccine SLVP020

• Sponsor: Stanford University (Other)
• Overall Status: Completed
• CT.gov ID: NCT01911065
• Collaborator: National Institute of Allergy and Infectious Diseases (NIAID) (NIH)
• Enrollment: 54
• Location: 1
• Arms: 2
• Duration (Months): 15
• Patients Per Site Per Month: 3.6

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Herpes Zoster	Biological: Zostavax™	Phase 4

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 54 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: T Cell Responses to Varicella Zoster Virus After Vaccination and Viral Escape
• Study Start Date: Sep 1, 2010
• Actual Primary Completion Date: Dec 1, 2011
• Actual Study Completion Date: Dec 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Zostavax™ vaccine group Participants > 50 years will receive a single dose 0.65 ml Zostavax™ (live, attenuated zoster vaccine) administered by subcutaneous injection.	Biological: Zostavax™; In the Vaccination arm, healthy individuals will be vaccinated with the licensed zoster vaccine, Zostavax.; Other Names: Zoster Vaccine Live
No Intervention: Natural-acquired VZV immunity Participants 40-49 years of age will 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).

Outcome Measures

Primary Outcome Measures

1. Number of Participants Who Received Zostavax Immunization or Had Natural Exposure to VZV [Day 0 to Day 35]

Secondary Outcome Measures

1. Number of Participants With Related Adverse Events [0 to 35 Days]

Other Outcome Measures

1. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years and Older
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stanford University School of Medicine	Stanford	California	United States	94305

Sponsors and Collaborators

• Stanford University
• National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

• Principal Investigator: Cornelia L Dekker, MD, Stanford University
• Principal Investigator: Jorg J Goronzy, MD, PhD, Stanford University

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Stanford LPCH Vaccine Program Clinical Trials Website

Publications

• Fang F, Yu M, Cavanagh MM, Hutter Saunders J, Qi Q, Ye Z, Le Saux S, Sultan W, Turgano E, Dekker CL, Tian L, Weyand CM, Goronzy JJ. Expression of CD39 on Activated T Cells Impairs their Survival in Older Individuals. Cell Rep. 2016 Feb 9;14(5):1218-1231. doi: 10.1016/j.celrep.2016.01.002. Epub 2016 Jan 28.
• Qi Q, Cavanagh MM, Le Saux S, NamKoong H, Kim C, Turgano E, Liu Y, Wang C, Mackey S, Swan GE, Dekker CL, Olshen RA, Boyd SD, Weyand CM, Tian L, Goronzy JJ. Diversification of the antigen-specific T cell receptor repertoire after varicella zoster vaccination. Sci Transl Med. 2016 Mar 30;8(332):332ra46. doi: 10.1126/scitranslmed.aaf1725.
• Qi Q, Cavanagh MM, Le Saux S, Wagar LE, Mackey S, Hu J, Maecker H, Swan GE, Davis MM, Dekker CL, Tian L, Weyand CM, Goronzy JJ. Defective T Memory Cell Differentiation after Varicella Zoster Vaccination in Older Individuals. PLoS Pathog. 2016 Oct 20;12(10):e1005892. doi: 10.1371/journal.ppat.1005892. eCollection 2016 Oct.
• Wang C, Liu Y, Cavanagh MM, Le Saux S, Qi Q, Roskin KM, Looney TJ, Lee JY, Dixit V, Dekker CL, Swan GE, Goronzy JJ, Boyd SD. B-cell repertoire responses to varicella-zoster vaccination in human identical twins. Proc Natl Acad Sci U S A. 2015 Jan 13;112(2):500-5. doi: 10.1073/pnas.1415875112. Epub 2014 Dec 22.

• Responsible Party: Cornelia L. Dekker, Professor, Pediatrics, Stanford University
• ClinicalTrials.gov Identifier: NCT01911065
• Other Study ID Numbers: SU-19385; 1U19AI090019-01
• First Posted: Jul 30, 2013
• Last Update Posted: Apr 21, 2017
• Last Verified: Apr 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Cornelia L. Dekker, Professor, Pediatrics, Stanford University: Herpes zoster; immune response; Zostavax; twins; non-twins
• Additional relevant MeSH terms: Herpes Zoster; Chickenpox; Vaccines

Study Results

Participant Flow

Arm/Group Title	Zostavax™ Vaccine Group	Naturally-acquired VZV Immunity
Arm/Group Description	Participants > 50 years received a single dose 0.65 ml Zostavax™ (live, attenuated zoster vaccine) administered by subcutaneous injection.	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).
Period Title: Overall Study
STARTED	45	9
COMPLETED	45	9
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Zostavax™ Vaccine Group	Naturally-acquired VZV Immunity	Total
Arm/Group Description	Participants > 50 years received a single dose 0.65 ml Zostavax™ (live, attenuated zoster vaccine) administered by subcutaneous injection.	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).	Total of all reporting groups
Overall Participants	45	9	54
Age, Customized (Count of Participants)
40-49 Years Old	0 0%	9 100%	9 16.7%
50 and above	45 100%	0 0%	45 83.3%
Sex: Female, Male (Count of Participants)
Female	21 46.7%	7 77.8%	28 51.9%
Male	24 53.3%	2 22.2%	26 48.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	3 6.7%	0 0%	3 5.6%
Not Hispanic or Latino	40 88.9%	9 100%	49 90.7%
Unknown or Not Reported	2 4.4%	0 0%	2 3.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	2 22.2%	2 3.7%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	43 95.6%	7 77.8%	50 92.6%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	2 4.4%	0 0%	2 3.7%
Region of Enrollment (participants) [Number]
United States	45 100%	9 100%	54 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants Who Received Zostavax Immunization or Had Natural Exposure to VZV
Time Frame	Day 0 to Day 35

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Zostavax™ Vaccine Group	Naturally-acquired VZV Immunity
Arm/Group Description	Participants > 50 years received a single dose 0.65 ml Zostavax™ (live, attenuated zoster vaccine) administered by subcutaneous injection.	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).
Measure Participants	45	9
Count of Participants [Participants]	45 100%	9 100%

2. Secondary Outcome

Title	Number of Participants With Related Adverse Events
Time Frame	0 to 35 Days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Zostavax™ Vaccine Group	Naturally-acquired VZV Immunity
Arm/Group Description	Participants > 50 years received a single dose 0.65 ml Zostavax™ (live, attenuated zoster vaccine) administered by subcutaneous injection.	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).
Measure Participants	45	9
Erythema at injection site greater 5 cm	5 11.1%	0 0%
No related AEs	40 88.9%	9 100%

3. Other Pre-specified Outcome

Title	Identify Predictors That Correlate With a Rapid and Diverse T Cell Response.
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Arm/Group Title	Zostavax™ Vaccine Group		Naturally-acquired VZV Immunity
Arm/Group Description	Participants > 50 years received a single dose 0.65 ml Zostavax™ (live, attenuated zoster vaccine) administered by subcutaneous injection.		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).
All Cause Mortality
	Zostavax™ Vaccine Group		Naturally-acquired VZV Immunity
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Zostavax™ Vaccine Group		Naturally-acquired VZV Immunity
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/45 (0%)		0/9 (0%)
Other (Not Including Serious) Adverse Events
	Zostavax™ Vaccine Group		Naturally-acquired VZV Immunity
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/45 (6.7%)		0/9 (0%)
Respiratory, thoracic and mediastinal disorders
Upper respiratory infection	2/45 (4.4%)	2	0/9 (0%)	0
Skin and subcutaneous tissue disorders
Herpes zoster	1/45 (2.2%)	1	0/9 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.