Immune System Diseases
Conditions
Keywords
varicella-zoster virus, vaccine, T-cell, genes, frail elderly, immunosenescence, immune and genetic correlates of response to zoster vaccine in the elderly
Brief summary
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.
Detailed description
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.
Interventions
DRUGZostavax
Sponsors
Merck Sharp & Dohme LLC
McMaster University
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
80 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* nursing home resident * greater than or equal to 80 years old * non-ambulatory
Exclusion criteria
* less than 80 years old * ambulatory * taking immunosuppressive medication * history of primary or acquired immuno-deficiency states including leukemia, other malignant neoplasms affecting the bone marrow or lymphatic system, and AIDS * active untreated tuberculosis * previous receipt of varicella vaccine * residents expected to expire within 30 days, in the opinion of the most responsible physician * residents planning to move nursing homes within the year * temporary residents
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in T-cell Response to the VZV Vaccine in the Frail Elderly | 6 weeks | 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. |
| Assessment of Immune Parameters Compatible With Inflammaging: CD4+/CD8+ Ratio | Baseline | 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. |
| Assessment of Immune Parameters Compatible With Inflammaging: High T Regulatory Cells | Baseline | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Assessment of Immune Parameters Compatible With Inflammaging: TEMRA Cells | Baseline | 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. |
| Assessment of Immune Parameters Compatible With Inflammaging: CD4 Cell Frequency | Baseline | 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. |
| Assessment of Immune Parameters Compatible With Inflammaging: High CD8+CD28CD45RA+T Cells | Baseline | 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. |
| Testing 150 Candidate Immune Response Genes for SNP Analysis | Baseline | 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 |
Countries
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Nursing Home Vaccine Group Nursing home residents \>= 80 years vaccinated with the ZOSTAVAX zoster vaccine | 191 |
| Community Control Vaccine Group Community dwelling seniors ages 60-75 years vaccinated with the Zostavax zoster vaccine | 50 |
| Total | 241 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 3 | 0 |
| Overall Study | Protocol Violation | 1 | 0 |
Baseline characteristics
| Characteristic | Community Control Vaccine Group | Nursing Home Vaccine Group | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 35 Participants | 191 Participants | 226 Participants |
| Age, Categorical Between 18 and 65 years | 15 Participants | 0 Participants | 15 Participants |
| Age, Continuous | 67.3 Years STANDARD_DEVIATION 4.34 | 89.0 Years STANDARD_DEVIATION 4.69 | 84.5 Years STANDARD_DEVIATION 9.9 |
| Region of Enrollment Canada | 50 Participants | 191 Participants | 241 Participants |
| Sex: Female, Male Female | 32 Participants | 154 Participants | 186 Participants |
| Sex: Female, Male Male | 18 Participants | 37 Participants | 55 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 23 / 191 | 11 / 50 |
| serious Total, serious adverse events | 3 / 191 | 0 / 50 |
Outcome results
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.
Time frame: Baseline
Population: Predictor variables were assessed only among the frail elderly, the community control group served as a control for immunogenicity only.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nursing Home Vaccine Group | Assessment of Immune Parameters Compatible With Inflammaging: CD4+/CD8+ Ratio | 3.06 T-cell ratio | Standard Deviation 2.38 |
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.
Time frame: Baseline
Population: Predictor variables were assessed only among the frail elderly, the community control group served as a control for immunogenicity only.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nursing Home Vaccine Group | Assessment of Immune Parameters Compatible With Inflammaging: High T Regulatory Cells | 2.23 % of peripheral blood mononuclear cell | Standard Deviation 1 |
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.
Time frame: 6 weeks
Population: IFN-gamma T cell ELISpot assay (sfu) against VZV taken prior to vaccination and 6 weeks post vaccination
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nursing Home Vaccine Group | Change From Baseline in T-cell Response to the VZV Vaccine in the Frail Elderly | Pre-vaccine IFN-gamma T cell ELISpot assay count | 50.17 Spot Forming Units per 10^6 PBMC | Standard Deviation 54.84 |
| Nursing Home Vaccine Group | Change From Baseline in T-cell Response to the VZV Vaccine in the Frail Elderly | Post- vaccine IFN-gamma T cell ELISpot assay count | 83.22 Spot Forming Units per 10^6 PBMC | Standard Deviation 72.56 |
| Community Control Vaccine Group | Change From Baseline in T-cell Response to the VZV Vaccine in the Frail Elderly | Pre-vaccine IFN-gamma T cell ELISpot assay count | 78.17 Spot Forming Units per 10^6 PBMC | Standard Deviation 65.37 |
| Community Control Vaccine Group | Change From Baseline in T-cell Response to the VZV Vaccine in the Frail Elderly | Post- vaccine IFN-gamma T cell ELISpot assay count | 120.56 Spot Forming Units per 10^6 PBMC | Standard Deviation 76.87 |
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.
Time frame: Baseline
Population: Predictor variables were assessed only among the frail elderly, the community control group served as a control for immunogenicity only.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nursing Home Vaccine Group | Assessment of Immune Parameters Compatible With Inflammaging: CD4 Cell Frequency | 65.24 % of peripheral blood mononuclear cell | Standard Deviation 15.41 |
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.
Time frame: Baseline
Population: Data not collected.
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.
Time frame: Baseline
Population: Data not collected.
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
Time frame: Baseline
Population: Genotyping was not conducted because of insufficient resources.