Effects of Chronic Viral Infection on Immune Response to Zoster Vaccination

• Sponsor: Rockefeller University (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02590068
• Collaborator: National Institute of Allergy and Infectious Diseases (NIAID) (NIH)
• Enrollment: 14
• Location: 1
• Arms: 2
• Actual Duration (Months): 21.3
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

This study aims to identify the innate and adaptive immune response to zoster vaccination. Half of the participants will be individuals with chronic hepatitis C, while the other half with healthy volunteers.The innate immune signature elicited by Zoster vaccination will be characterized by RNA-seq analysis of pre- and post-vaccination RNA from whole blood. We will compare fold changes in gene expression profiles pre- versus post-vaccination in each individual, as well as between the two arms of the study. RNA-seq will be used to assess innate immune activation by evaluating the changes to the expression levels of interferon-stimulated genes pre- and post-vaccination. Adaptive immune response will be determined by the traditional correlates of protection used in previous Zoster clinical studies in addition to flow cytometry24. Correlates of protection include antibody response, interferon gamma production and the frequency of responder cells post- vaccination24. For antibody production, we will perform Zoster glycoprotein ELISA (gpELISA) targeting IgG/IgM. The number and frequency of responder cells will be characterized by flow cytometry.

Condition or Disease	Intervention/Treatment	Phase
Hepatitis C	Drug: Zoster vaccine live	N/A

Detailed Description

Chronic HCV infection is associated with persistent innate immune activation and dampened cellular immune responses. Interferons (IFNs) are key mediators of the antiviral innate immune response, initiating the expression of interferon-stimulated genes (ISG) with numerous host protective effector functions. However, in chronic HCV, high pre-therapy expression of ISG and persistent activation of the innate immune system negatively predicts the response to IFN-based therapies and failure of viral clearance8. In addition, HCV persistence is also associated with HCV-specific-CD8+ T cell exhaustion. HCV-specific CD8+ T cell exhaustion is characterized by diminished ex vivo polyfunctionality, upregulation of negative costimulatory cell modulators and, decreased cellular proliferation and IFN production10,12. This phenotype is associated with the development of short-term effector CD8+ T cells rather than durable, long-term memory CD8+ T cells. Chronic bystander infections (e.g. chronic HCV), characterized by persistent inflammation have been linked to bystander (non-HCV specific) CD8+ T cell dysfunction. Bystander CD8+ T cell dysfunction significantly impairs the expansion of memory CD8+ T cells and could prevent the development of secondary immunological memory to new antigens and/or vaccines11,13. Clinically, chronic HCV has been associated with impaired immune response to Hepatitis B vaccination13,14,15. Only 40% to 60% of individuals with chronic HCV achieve seroprotective titers following HBV vaccination versus 90% to 95% in healthy subjects13,14. Specific immune defects responsible for HBV vaccine failure in HCV-infected patients are unknown at present. However, some studies have suggested that the blunting of the immune response to HBV vaccination is associated with lymphocyte dysfunction and upregulation of PD-1 expression on CD4+ T cells in HBV vaccine non-responders13,15.

In the United States, 99.5% of adults over 40 years have been infected with the Varicella zoster virus (VZV) and are at risk of Zoster virus reactivation (shingles) and its complications. Unilateral, painful, blistering rashes along dermatomes characterize shingles. Complications associated with shingles include acute or chronic pain, osteonecrosis, zoster ophthalmicus with visual impairment, increased risk of blindness and a 4-fold risk of cerebral vasculitis-associated stroke)1,2. Overall, complications of shingles have a negative impact on the quality of life and activities of daily living21,22. Zoster vaccine live (Zostavax®, Merck) is recommended for the prevention of shingles. Zoster vaccine is a live, attenuated vaccine that is licensed by the FDA for individuals older than 50 years without an underlying immune deficiency (HIV, malignancies, immunosuppression and transplantation). In non-immunocompromised individuals, Zoster vaccine decreases shingles by 51% in individuals between ages 60 - 89 years and 70% in individuals between 50 - 59 years of age. Chronic infections such as TB, malaria and chronic Hepatitis C virus (HCV) have been associated with increased susceptibility to other pathogens and decreased vaccination efficacy3-6. Although chronic HCV infection is not considered a clinically immunocompromised state, it is associated with persistent immune activation and decreased vaccination response7. Zostavax is routinely administered to chronic HCV patients. However, at present, no other study has documented the immune responses elicited by Zoster vaccination in this population. This study aims to identify the innate and adaptive immune signatures elicited by zoster vaccination in chronic HCV and healthy volunteers. Unrecognized suboptimal vaccine response in individuals with chronic immune dysregulated states (chronic bystander viral infections (HBV, HCV and HIV with CD4 >200), diabetes, advancing age, cancers and transplantation) could be potentially devastating and costly.

Study Design

• Study Type: Interventional
• Actual Enrollment: 14 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Effects of Chronic Viral Infection on Immune Response to Zoster Vaccination
• Actual Study Start Date: Dec 1, 2015
• Actual Primary Completion Date: Sep 8, 2017
• Actual Study Completion Date: Sep 8, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Hepatitis C infected volunteers Zoster vaccine live (Zostavax), 0.65 ml dose, administered subcutaneously to Hepatitis C infected volunteers	Drug: Zoster vaccine live; Single Zostavax vaccine, 0.65 ml dose, administered subcutaneously; Other Names: Zostavax
Active Comparator: Healthy volunteers Zoster vaccine live (Zostavax), 0.65 ml dose, administered subcutaneously to healthy volunteers	Drug: Zoster vaccine live; Single Zostavax vaccine, 0.65 ml dose, administered subcutaneously; Other Names: Zostavax

Outcome Measures

Primary Outcome Measures

1. Serum Zoster Antibody Level [18 months]

   Serum zoster antibody level would be measured by gpELISA expressed in (units/mL)

Secondary Outcome Measures

1. Interferon Stimulated Gene (ISG) Expression [18 months]

   Interferon stimulated gene (ISG) expression in PBMC will be expressed as fold-change (FCH) above baseline

2. Serum Biomarkers of Immune Activation(Expressed in%) [18 months]

   Serum biomarkers of immune activation will be measured and expressed in percentage.

3. Responder Cell Frequency [18 months]

   Responder cell frequency: VZV specific CD4+ T cells post-vaccination (expressed in %)

4. Interferon-gamma Response [18 months]

   Interferon-gamma response: by ELIspot expressed as number of spot-forming cells per million PBMCs

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Willing to receive the herpes zoster vaccine

• Volunteer chronically infected with HCV (as demonstrated by serology testing and have a viral load >1000 copies) without treatment

• Healthy volunteer without significant medical problems

Exclusion Criteria:

• Received any vaccine within a month prior to study vaccine

• Previous Zoster infection as an adult, >18 years

• HIV or Hepatitis B virus infection in the HCV and healthy arms

• For HCV-negative, healthy volunteers: History of HCV infection or positive HCV antibody test

• Participation in another clinical study of an investigational product currently or within the past 90 days, or expected particpation during this study

• In the opinion of the investigator, the volunteer is unlikely to comply with the study protocol

• Any clinically significant abnormality or medical history or physical examination including history of immunodeficiency or autoimmune disease (in addition to HCV infection, for HCV group)

• Currently taking systemic steroids or other immunomodulatory medications including anticancer medications and antiviral medications

• Any clinically significant acute or chronic medical condition requiring care by a primary care provider (e.g., diabetes, coronary artery disease, rheumatologic illness, malignancy, substance abuse) that, in the opinion of the investigator, would preclude participation

• Male or female < 50 and > 70 years of age

• Is pregnant or lactating

• Clinical, laboratory, or biopsy evidence of cirrhosis

• Allergy to gelatin and/or neomycin

• ALT and/or AST > 3.5 times the ULN

• Immunosuppressed or immunodeficient individuals including those with a history of primary or acquired immunodeficiency states, leukemia, lymphoma or other malignant neoplasms affecting the bone marrow or lymphatic system and those on immunosuppressive therapy

• Individuals with active untreated tuberculosis

• Prior Varicella vaccination

• HCV volunteers who have a viral load of <1000 copies

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Rockefeller University Hospital	New York	New York	United States	10065

Sponsors and Collaborators

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

Investigators

• Principal Investigator: Oyebisi Jegede, MBBS, PhD, The Rockefeller University Center for Clinical and Translational Studies

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - May 15, 2019

More Information

Publications

• Abu-Raddad LJ, Patnaik P, Kublin JG. Dual infection with HIV and malaria fuels the spread of both diseases in sub-Saharan Africa. Science. 2006 Dec 8;314(5805):1603-6. Erratum in: Science. 2007 Feb 2;315(5812):598.
• Bahgat MM, El-Far MA, Mesalam AA, Ismaeil AA, Ibrahim AA, Gewaid HE, Maghraby AS, Ali MA, Abd-Elshafy DN. Schistosoma mansoni soluble egg antigens enhance HCV replication in mammalian cells. J Infect Dev Ctries. 2010 May 1;4(4):226-34.
• Crawford A, Angelosanto JM, Kao C, Doering TA, Odorizzi PM, Barnett BE, Wherry EJ. Molecular and transcriptional basis of CD4⁺ T cell dysfunction during chronic infection. Immunity. 2014 Feb 20;40(2):289-302. doi: 10.1016/j.immuni.2014.01.005. Epub 2014 Feb 13.
• Drolet M, Levin MJ, Schmader KE, Johnson R, Oxman MN, Patrick D, Fournier SO, Mansi JA, Brisson M. Employment related productivity loss associated with herpes zoster and postherpetic neuralgia: a 6-month prospective study. Vaccine. 2012 Mar 9;30(12):2047-50. doi: 10.1016/j.vaccine.2012.01.045. Epub 2012 Jan 28.
• Law CW, Chen Y, Shi W, Smyth GK. voom: Precision weights unlock linear model analysis tools for RNA-seq read counts. Genome Biol. 2014 Feb 3;15(2):R29. doi: 10.1186/gb-2014-15-2-r29.
• Levin MJ, Smith JG, Kaufhold RM, Barber D, Hayward AR, Chan CY, Chan IS, Li DJ, Wang W, Keller PM, Shaw A, Silber JL, Schlienger K, Chalikonda I, Vessey SJ, Caulfield MJ. Decline in varicella-zoster virus (VZV)-specific cell-mediated immunity with increasing age and boosting with a high-dose VZV vaccine. J Infect Dis. 2003 Nov 1;188(9):1336-44. Epub 2003 Oct 17.
• Lin F, Hadler JL. Epidemiology of primary varicella and herpes zoster hospitalizations: the pre-varicella vaccine era. J Infect Dis. 2000 Jun;181(6):1897-905. Epub 2000 Jun 5. Erratum in: J Infect Dis. 2013 May 15;207(10):1625.
• Maecker HT, McCoy JP, Nussenblatt R. Standardizing immunophenotyping for the Human Immunology Project. Nat Rev Immunol. 2012 Feb 17;12(3):191-200. doi: 10.1038/nri3158. Review. Erratum in: Nat Rev Immunol. 2012 Jun;12(6):471.
• Metz P, Dazert E, Ruggieri A, Mazur J, Kaderali L, Kaul A, Zeuge U, Windisch MP, Trippler M, Lohmann V, Binder M, Frese M, Bartenschlager R. Identification of type I and type II interferon-induced effectors controlling hepatitis C virus replication. Hepatology. 2012 Dec;56(6):2082-93. doi: 10.1002/hep.25908. Epub 2012 Oct 14.
• Moorman JP, Zhang CL, Ni L, Ma CJ, Zhang Y, Wu XY, Thayer P, Islam TM, Borthwick T, Yao ZQ. Impaired hepatitis B vaccine responses during chronic hepatitis C infection: involvement of the PD-1 pathway in regulating CD4(+) T cell responses. Vaccine. 2011 Apr 12;29(17):3169-76. doi: 10.1016/j.vaccine.2011.02.052. Epub 2011 Mar 3.
• Oxman MN, Levin MJ, Johnson GR, Schmader KE, Straus SE, Gelb LD, Arbeit RD, Simberkoff MS, Gershon AA, Davis LE, Weinberg A, Boardman KD, Williams HM, Zhang JH, Peduzzi PN, Beisel CE, Morrison VA, Guatelli JC, Brooks PA, Kauffman CA, Pachucki CT, Neuzil KM, Betts RF, Wright PF, Griffin MR, Brunell P, Soto NE, Marques AR, Keay SK, Goodman RP, Cotton DJ, Gnann JW Jr, Loutit J, Holodniy M, Keitel WA, Crawford GE, Yeh SS, Lobo Z, Toney JF, Greenberg RN, Keller PM, Harbecke R, Hayward AR, Irwin MR, Kyriakides TC, Chan CY, Chan IS, Wang WW, Annunziato PW, Silber JL; Shingles Prevention Study Group. A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults. N Engl J Med. 2005 Jun 2;352(22):2271-84.
• Pisell TL, Hoffman IF, Jere CS, Ballard SB, Molyneux ME, Butera ST, Lawn SD. Immune activation and induction of HIV-1 replication within CD14 macrophages during acute Plasmodium falciparum malaria coinfection. AIDS. 2002 Jul 26;16(11):1503-9.
• Sauerbrei A, Wutzler P. Serological detection of varicella-zoster virus-specific immunoglobulin G by an enzyme-linked immunosorbent assay using glycoprotein antigen. J Clin Microbiol. 2006 Sep;44(9):3094-7.
• Schmader KE, Johnson GR, Saddier P, Ciarleglio M, Wang WW, Zhang JH, Chan IS, Yeh SS, Levin MJ, Harbecke RM, Oxman MN; Shingles Prevention Study Group. Effect of a zoster vaccine on herpes zoster-related interference with functional status and health-related quality-of-life measures in older adults. J Am Geriatr Soc. 2010 Sep;58(9):1634-41. doi: 10.1111/j.1532-5415.2010.03021.x.
• Schoggins JW, Wilson SJ, Panis M, Murphy MY, Jones CT, Bieniasz P, Rice CM. A diverse range of gene products are effectors of the type I interferon antiviral response. Nature. 2011 Apr 28;472(7344):481-5. doi: 10.1038/nature09907. Epub 2011 Apr 10. Erratum in: Nature. 2015 Sep 3;525(7567):144.
• Soneson C, Delorenzi M. A comparison of methods for differential expression analysis of RNA-seq data. BMC Bioinformatics. 2013 Mar 9;14:91. doi: 10.1186/1471-2105-14-91.
• Stelekati E, Shin H, Doering TA, Dolfi DV, Ziegler CG, Beiting DP, Dawson L, Liboon J, Wolski D, Ali MA, Katsikis PD, Shen H, Roos DS, Haining WN, Lauer GM, Wherry EJ. Bystander chronic infection negatively impacts development of CD8(+) T cell memory. Immunity. 2014 May 15;40(5):801-13. doi: 10.1016/j.immuni.2014.04.010.
• Stelekati E, Wherry EJ. Chronic bystander infections and immunity to unrelated antigens. Cell Host Microbe. 2012 Oct 18;12(4):458-69. doi: 10.1016/j.chom.2012.10.001. Review.
• Urbani S, Amadei B, Tola D, Massari M, Schivazappa S, Missale G, Ferrari C. PD-1 expression in acute hepatitis C virus (HCV) infection is associated with HCV-specific CD8 exhaustion. J Virol. 2006 Nov;80(22):11398-403. Epub 2006 Sep 6.
• Wherry EJ, Ha SJ, Kaech SM, Haining WN, Sarkar S, Kalia V, Subramaniam S, Blattman JN, Barber DL, Ahmed R. Molecular signature of CD8+ T cell exhaustion during chronic viral infection. Immunity. 2007 Oct;27(4):670-84. Epub 2007 Oct 18. Erratum in: Immunity. 2007 Nov;27(5):824.
• Wiedmann M, Liebert UG, Oesen U, Porst H, Wiese M, Schroeder S, Halm U, Mössner J, Berr F. Decreased immunogenicity of recombinant hepatitis B vaccine in chronic hepatitis C. Hepatology. 2000 Jan;31(1):230-4.
• Zhu J, Hladik F, Woodward A, Klock A, Peng T, Johnston C, Remington M, Magaret A, Koelle DM, Wald A, Corey L. Persistence of HIV-1 receptor-positive cells after HSV-2 reactivation is a potential mechanism for increased HIV-1 acquisition. Nat Med. 2009 Aug;15(8):886-92. doi: 10.1038/nm.2006. Epub 2009 Aug 2.

• Responsible Party: Rockefeller University
• ClinicalTrials.gov Identifier: NCT02590068
• Other Study ID Numbers: OJE-0890; 5U19AI111825-02
• First Posted: Oct 28, 2015
• Last Update Posted: Dec 18, 2019
• Last Verified: Dec 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Hepatitis C; Virus Diseases

Study Results

Participant Flow

Arm/Group Title	Hepatitis C Infected Volunteers	Healthy Volunteers
Arm/Group Description	Zoster vaccine live (Zostavax), 0.65 ml dose, administered subcutaneously to Hepatitis C infected volunteers Zoster vaccine live: Single Zostavax vaccine, 0.65 ml dose, administered subcutaneously	Zoster vaccine live (Zostavax), 0.65 ml dose, administered subcutaneously to healthy volunteers Zoster vaccine live: Single Zostavax vaccine, 0.65 ml dose, administered subcutaneously
Period Title: Overall Study
STARTED	0	14
COMPLETED	0	14
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Hepatitis C Infected Volunteers	Healthy Volunteers	Total
Arm/Group Description	Zoster vaccine live (Zostavax), 0.65 ml dose, administered subcutaneously to Hepatitis C infected volunteers Zoster vaccine live: Single Zostavax vaccine, 0.65 ml dose, administered subcutaneously	Zoster vaccine live (Zostavax), 0.65 ml dose, administered subcutaneously to healthy volunteers Zoster vaccine live: Single Zostavax vaccine, 0.65 ml dose, administered subcutaneously	Total of all reporting groups
Overall Participants	0	14	14
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	57	57
Sex: Female, Male (Count of Participants)
Female	4 Infinity	4 28.6%
Male	10 Infinity	10 71.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 Infinity	2 14.3%
Not Hispanic or Latino	11 Infinity	11 78.6%
Unknown or Not Reported	1 Infinity	1 7.1%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 Infinity	1 7.1%
Asian	0 NaN	0 0%
Native Hawaiian or Other Pacific Islander	0 NaN	0 0%
Black or African American	5 Infinity	5 35.7%
White	6 Infinity	6 42.9%
More than one race	1 Infinity	1 7.1%
Unknown or Not Reported	1 Infinity	1 7.1%
Region of Enrollment (Count of Participants)
United States	14 Infinity	14 100%

Outcome Measures

1. Primary Outcome

Title	Serum Zoster Antibody Level
Description	Serum zoster antibody level would be measured by gpELISA expressed in (units/mL)
Time Frame	18 months

Outcome Measure Data

Analysis Population Description

Samples were collected but none were tested for antibody levels

Arm/Group Title	Hepatitis C Infected Volunteers	Healthy Volunteers
Arm/Group Description	Zoster vaccine live (Zostavax), 0.65 ml dose, administered subcutaneously to Hepatitis C infected volunteers Zoster vaccine live: Single Zostavax vaccine, 0.65 ml dose, administered subcutaneously	Zoster vaccine live (Zostavax), 0.65 ml dose, administered subcutaneously to healthy volunteers Zoster vaccine live: Single Zostavax vaccine, 0.65 ml dose, administered subcutaneously
Measure Participants	0	0

2. Secondary Outcome

Title	Interferon Stimulated Gene (ISG) Expression
Description	Interferon stimulated gene (ISG) expression in PBMC will be expressed as fold-change (FCH) above baseline
Time Frame	18 months

Outcome Measure Data

Analysis Population Description

Samples were collected and cryopreserved. RNA was collected for these samples and batched, but the RNA-Seq (for RNA expression measurements) was not run. The samples wee not analyzed and no assays were performed for this protocol.

Arm/Group Title	Hepatitis C Infected Volunteers	Healthy Volunteers
Arm/Group Description	Zoster vaccine live (Zostavax), 0.65 ml dose, administered subcutaneously to Hepatitis C infected volunteers Zoster vaccine live: Single Zostavax vaccine, 0.65 ml dose, administered subcutaneously	Zoster vaccine live (Zostavax), 0.65 ml dose, administered subcutaneously to healthy volunteers Zoster vaccine live: Single Zostavax vaccine, 0.65 ml dose, administered subcutaneously
Measure Participants	0	0

3. Secondary Outcome

Title	Serum Biomarkers of Immune Activation(Expressed in%)
Description	Serum biomarkers of immune activation will be measured and expressed in percentage.
Time Frame	18 months

Outcome Measure Data

Analysis Population Description

Samples were not analyzed and no assays were performed for this protocol.

Arm/Group Title	Hepatitis C Infected Volunteers	Healthy Volunteers
Arm/Group Description	Zoster vaccine live (Zostavax), 0.65 ml dose, administered subcutaneously to Hepatitis C infected volunteers Zoster vaccine live: Single Zostavax vaccine, 0.65 ml dose, administered subcutaneously	Zoster vaccine live (Zostavax), 0.65 ml dose, administered subcutaneously to healthy volunteers Zoster vaccine live: Single Zostavax vaccine, 0.65 ml dose, administered subcutaneously
Measure Participants	0	0

4. Secondary Outcome

Title	Responder Cell Frequency
Description	Responder cell frequency: VZV specific CD4+ T cells post-vaccination (expressed in %)
Time Frame	18 months

Outcome Measure Data

Analysis Population Description

Samples were not analyzed and no assays were performed for this protocol.

Arm/Group Title	Hepatitis C Infected Volunteers	Healthy Volunteers
Arm/Group Description	Zoster vaccine live (Zostavax), 0.65 ml dose, administered subcutaneously to Hepatitis C infected volunteers Zoster vaccine live: Single Zostavax vaccine, 0.65 ml dose, administered subcutaneously	Zoster vaccine live (Zostavax), 0.65 ml dose, administered subcutaneously to healthy volunteers Zoster vaccine live: Single Zostavax vaccine, 0.65 ml dose, administered subcutaneously
Measure Participants	0	0

5. Secondary Outcome

Title	Interferon-gamma Response
Description	Interferon-gamma response: by ELIspot expressed as number of spot-forming cells per million PBMCs
Time Frame	18 months

Outcome Measure Data

Analysis Population Description

Samples were not analyzed and no assays were performed for this protocol.

Arm/Group Title	Hepatitis C Infected Volunteers	Healthy Volunteers
Arm/Group Description	Zoster vaccine live (Zostavax), 0.65 ml dose, administered subcutaneously to Hepatitis C infected volunteers Zoster vaccine live: Single Zostavax vaccine, 0.65 ml dose, administered subcutaneously	Zoster vaccine live (Zostavax), 0.65 ml dose, administered subcutaneously to healthy volunteers Zoster vaccine live: Single Zostavax vaccine, 0.65 ml dose, administered subcutaneously
Measure Participants	0	0

Adverse Events

Time Frame	Up to 22 months
Adverse Event Reporting Description	The number of participants at risk in the Hepatitis C Infected Volunteers group is zero as we didn't enroll any volunteers in that arm of the study and the study is now closed for enrollment.
Arm/Group Title	Hepatitis C Infected Volunteers		Healthy Volunteers
Arm/Group Description	Zoster vaccine live (Zostavax), 0.65 ml dose, administered subcutaneously to Hepatitis C infected volunteers Zoster vaccine live: Single Zostavax vaccine, 0.65 ml dose, administered subcutaneously		Zoster vaccine live (Zostavax), 0.65 ml dose, administered subcutaneously to healthy volunteers Zoster vaccine live: Single Zostavax vaccine, 0.65 ml dose, administered subcutaneously
All Cause Mortality
	Hepatitis C Infected Volunteers		Healthy Volunteers
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/14 (0%)
Serious Adverse Events
	Hepatitis C Infected Volunteers		Healthy Volunteers
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		1/14 (7.1%)
Cardiac disorders
Dyspnea	0/0 (NaN)	0	1/14 (7.1%)	1
Chest Pain	0/0 (NaN)	0	1/14 (7.1%)	1
Other (Not Including Serious) Adverse Events
	Hepatitis C Infected Volunteers		Healthy Volunteers
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		4/14 (28.6%)
Blood and lymphatic system disorders
Mild Anemia	0/0 (NaN)	0	1/14 (7.1%)	1
Gastrointestinal disorders
Dental Filling Fell Out	0/0 (NaN)	0	1/14 (7.1%)	1
General disorders
Lightheadedness	0/0 (NaN)	0	1/14 (7.1%)	1
Musculoskeletal and connective tissue disorders
Mild Back Pain	0/0 (NaN)	0	1/14 (7.1%)	1
Psychiatric disorders
Anxiety	0/0 (NaN)	0	1/14 (7.1%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.