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| Name | Class |
|---|---|
| Merck Sharp & Dohme LLC | INDUSTRY |
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This study is being done to evaluate the zoster vaccine response in the nursing home elderly (80 years or older). As the immune system ages, the response to vaccines is not always as strong as in younger people. Previous zoster vaccine studies have excluded nursing home residents so the vaccine effect in this population is not known. Furthermore, the immune and genetic reasons as to why the vaccine works well in some people but not in others are also unknown. The goal of this study is to evaluate why some immune systems respond well to the vaccine and why others do not.
Deleterious changes in immunity that occur with aging are known as immunosenescence. Such changes, particularly in adaptive immunity, may lead to an impaired vaccine response in the elderly. Characterizing the immune determinants and the genetic basis for vaccine response in the frail elderly is a practical approach to better our understanding of immunosenescence. Data on genetic determinants to immunization are sparse, furthermore, to the best of our knowledge, none exist in the elderly. In this pilot study, we propose studying the immune response to the herpes zoster vaccine and the underlying genetic determinants of the immune response in elderly residents of nursing homes.
The three specific aims of this study are to generate data in order to 1) assess the T-cell response to the varicella-zoster virus (VZV) vaccine in the frail elderly; 2) assess whether immune (T-cell) phenotypes are associated with a response; 3) test the association between immune response genotype sets and T-cell response. We hypothesize that response to the VZV vaccine in elderly nonambulatory nursing home residents is a function of characteristic T-cell immune phenotypes prior to vaccination and that there are immune genetic polymorphisms associated with the response. This study will allow us to generate preliminary data and establish feasibility in order to address these questions fully in a larger population in a subsequent grant application.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Nursing Home Elderly Cases | Non-ambulatory nursing home residents >= 80 years old will be vaccinated with the zoster vaccine and provide baseline and post-vaccination blood samples. We will assess differences in genotype frequencies between participants with high and low RCF and ELISPOT responses using a candidate gene approach with SNPs (single nucleotide polymorphisms). A case will be considered failure to mount a high response. |
| |
| Nursing Home Elderly Controls | Non-ambulatory nursing home residents >= 80 years old will be vaccinated with the zoster vaccine and provide baseline and post-vaccination blood samples. We will assess differences in genotype frequencies between participants with high and low RCF and ELISPOT responses using a candidate gene approach with SNPs. A control will be a participant who mounted an adequate response as defined in primary outcomes. |
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| Community dwelling seniors | Community dwelling seniors ages 60-75 will be enrolled as a control group for the laboratory testing. They will be vaccinated and will provide pre- and post-vaccination blood. If nursing home residents do not show a response it is important to know that it is not a failure of the laboratory's measurement of immunogenicity. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Zostavax | Drug |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in T-cell Response to the VZV Vaccine in the Frail Elderly | As the primary phenotype, we will compare change in Enzyme-linked immunosorbent spot (ELISPOT) from baseline (i.e., pre and post vaccination). A high baseline T cell response will be defined as ELISPOT = >50 spots and a low baseline response will be ELISPOT = <10 spots. | 6 weeks |
| Assessment of Immune Parameters Compatible With Inflammaging: CD4+/CD8+ Ratio | Characterization of T-cell populations will be conducted on whole blood using multi-parametric flow cytometry prior to immunization to characterize the immunological function of circulating T-cells in the nursing home vaccine group. | Baseline |
| Assessment of Immune Parameters Compatible With Inflammaging: High T Regulatory Cells | Characterization of T-cell populations will be conducted on whole blood using multi-parametric flow cytometry prior to immunization to characterize the immunological function of circulating T-cells in the nursing home vaccine group. | Baseline |
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| Measure | Description | Time Frame |
|---|---|---|
| Assessment of Immune Parameters Compatible With Inflammaging: TEMRA Cells | Characterization of Tcell populations will be conducted on whole blood using multiparametric flow cytometry prior to immunization to characterize the immunological function of circulating Tcells in each participant. | Baseline |
| Assessment of Immune Parameters Compatible With Inflammaging: High CD8+CD28CD45RA+T Cells |
Inclusion Criteria:
Exclusion Criteria:
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Elderly, non-ambulatory residents of nursing homes.
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| Name | Affiliation | Role |
|---|---|---|
| Mark B. Loeb, FRCPC,MD,MSc | McMaster University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Macassa Lodge | Hamilton | Ontario | Canada |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 27707807 | Derived | Lelic A, Verschoor CP, Lau VW, Parsons R, Evelegh C, Bowdish DM, Bramson JL, Loeb MB. Immunogenicity of Varicella Vaccine and Immunologic Predictors of Response in a Cohort of Elderly Nursing Home Residents. J Infect Dis. 2016 Dec 15;214(12):1905-1910. doi: 10.1093/infdis/jiw462. Epub 2016 Oct 5. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Nursing Home Vaccine Group | Nursing home residents >= 80 years vaccinated with the ZOSTAVAX zoster vaccine |
| FG001 | Community Control Vaccine Group | Community dwelling seniors ages 60-75 years vaccinated with the Zostavax zoster vaccine |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | Nursing Home Vaccine Group | Nursing home residents >= 80 years vaccinated with the ZOSTAVAX zoster vaccine |
| BG001 | Community Control Vaccine Group | Community dwelling seniors ages 60-75 years vaccinated with the Zostavax zoster vaccine |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change From Baseline in T-cell Response to the VZV Vaccine in the Frail Elderly | As the primary phenotype, we will compare change in Enzyme-linked immunosorbent spot (ELISPOT) from baseline (i.e., pre and post vaccination). A high baseline T cell response will be defined as ELISPOT = >50 spots and a low baseline response will be ELISPOT = <10 spots. | IFN-gamma T cell ELISpot assay (sfu) against VZV taken prior to vaccination and 6 weeks post vaccination | Posted | Mean | Standard Deviation | Spot Forming Units per 10^6 PBMC | 6 weeks |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Nursing Home Vaccine Group | Nursing home residents >= 80 years vaccinated with the ZOSTAVAX zoster vaccine |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pre-existing fragile health and advanced age | General disorders | Systematic Assessment | Non-vaccine related death |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cough | General disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Mark Loeb | McMaster University | 905 515 9140 | 26679 | loebm@mcmaster.ca |
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| ID | Term |
|---|---|
| D007154 | Immune System Diseases |
| D002644 | Chickenpox |
| ID | Term |
|---|---|
| D000073618 | Varicella Zoster Virus Infection |
| D006566 | Herpesviridae Infections |
| D004266 | DNA Virus Infections |
| D014777 | Virus Diseases |
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| ID | Term |
|---|---|
| D053061 | Herpes Zoster Vaccine |
| ID | Term |
|---|---|
| D019433 | Chickenpox Vaccine |
| D022283 | Herpesvirus Vaccines |
| D014765 | Viral Vaccines |
| D014612 | Vaccines |
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Retained specimens include DNA and blood cells.
Characterization of Tcell populations will be conducted on whole blood using multiparametric flow cytometry prior to immunization to characterize the immunological function of circulating Tcells in each participant. |
| Baseline |
| Testing 150 Candidate Immune Response Genes for SNP Analysis | These will include Tolllike receptors, cytokines, chemokines, chemokine receptors, interferons and interferon receptors. Tolllike receptors: TLR1TLR9 Cytokines: ILI1A, ILI1B, IL1RN, IL4, IL5, IL12B, IL13, CSF2 Chemokines: CCL1CCL3, CCL3L1, CCL4CCL8, CCL11, CCL13, CCL15CCL28, CXCL1CXCL14, CXCL16, CX3CL1 Chemokine receptors: CCR1CCR10, CXCR1CXCR6, CX3CR1, XCR1XCR2 Interferons: IFNA1IFNA2, IFNA4IFNA8, IFNA10, IFNA13, IFNA14, IFNA16IFNA17, IFNA21, IFNB1, IFNB3, IFNG, IFNK, IFNW1 Interferon receptors: IFNAR1, IFNAR2, IFNGR1, IFNGR2 | Baseline |
| Assessment of Immune Parameters Compatible With Inflammaging: CD4 Cell Frequency | Characterization of T-cell populations will be conducted on whole blood using multi-parametric flow cytometry prior to immunization to characterize the immunological function of circulating T-cells in the nursing home vaccine group. | Baseline |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | Participants |
|
Community dwelling seniors ages 60-75 years vaccinated with the Zostavax zoster vaccine |
|
|
| Primary | Assessment of Immune Parameters Compatible With Inflammaging: CD4+/CD8+ Ratio | Characterization of T-cell populations will be conducted on whole blood using multi-parametric flow cytometry prior to immunization to characterize the immunological function of circulating T-cells in the nursing home vaccine group. | Predictor variables were assessed only among the frail elderly, the community control group served as a control for immunogenicity only. | Posted | Mean | Standard Deviation | T-cell ratio | Baseline |
|
|
|
| Primary | Assessment of Immune Parameters Compatible With Inflammaging: High T Regulatory Cells | Characterization of T-cell populations will be conducted on whole blood using multi-parametric flow cytometry prior to immunization to characterize the immunological function of circulating T-cells in the nursing home vaccine group. | Predictor variables were assessed only among the frail elderly, the community control group served as a control for immunogenicity only. | Posted | Mean | Standard Deviation | % of peripheral blood mononuclear cell | Baseline |
|
|
|
| Other Pre-specified | Assessment of Immune Parameters Compatible With Inflammaging: TEMRA Cells | Characterization of Tcell populations will be conducted on whole blood using multiparametric flow cytometry prior to immunization to characterize the immunological function of circulating Tcells in each participant. | Data not collected. | Posted | Baseline |
|
|
| Other Pre-specified | Assessment of Immune Parameters Compatible With Inflammaging: High CD8+CD28CD45RA+T Cells | Characterization of Tcell populations will be conducted on whole blood using multiparametric flow cytometry prior to immunization to characterize the immunological function of circulating Tcells in each participant. | Data not collected. | Posted | Baseline |
|
|
| Other Pre-specified | Testing 150 Candidate Immune Response Genes for SNP Analysis | These will include Tolllike receptors, cytokines, chemokines, chemokine receptors, interferons and interferon receptors. Tolllike receptors: TLR1TLR9 Cytokines: ILI1A, ILI1B, IL1RN, IL4, IL5, IL12B, IL13, CSF2 Chemokines: CCL1CCL3, CCL3L1, CCL4CCL8, CCL11, CCL13, CCL15CCL28, CXCL1CXCL14, CXCL16, CX3CL1 Chemokine receptors: CCR1CCR10, CXCR1CXCR6, CX3CR1, XCR1XCR2 Interferons: IFNA1IFNA2, IFNA4IFNA8, IFNA10, IFNA13, IFNA14, IFNA16IFNA17, IFNA21, IFNB1, IFNB3, IFNG, IFNK, IFNW1 Interferon receptors: IFNAR1, IFNAR2, IFNGR1, IFNGR2 | Genotyping was not conducted because of insufficient resources. | Posted | Baseline |
|
|
| Other Pre-specified | Assessment of Immune Parameters Compatible With Inflammaging: CD4 Cell Frequency | Characterization of T-cell populations will be conducted on whole blood using multi-parametric flow cytometry prior to immunization to characterize the immunological function of circulating T-cells in the nursing home vaccine group. | Predictor variables were assessed only among the frail elderly, the community control group served as a control for immunogenicity only. | Posted | Mean | Standard Deviation | % of peripheral blood mononuclear cell | Baseline |
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| 3 |
| 191 |
| 23 |
| 191 |
| EG001 | Community Control Vaccine Group | Community dwelling seniors ages 60-75 years vaccinated with the Zostavax zoster vaccine | 0 | 50 | 11 | 50 |
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| Progressive renal failure | Renal and urinary disorders | Systematic Assessment | Non-vaccine related death |
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| Advanced age and medical issues (Parkinson's disease) | Nervous system disorders | Systematic Assessment | Non-vaccine related death |
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| Fall | General disorders | Systematic Assessment |
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| Lethargy | General disorders | Systematic Assessment |
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| Emesis/Nausea | General disorders | Systematic Assessment |
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| Pain/Soreness in arm | General disorders | Systematic Assessment |
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| Redness/Swelling in arm | General disorders | Systematic Assessment |
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| Headache | General disorders | Systematic Assessment |
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| D007239 | Infections |
| D001688 |
| Biological Products |
| D045424 | Complex Mixtures |