Influenza Vaccine Responses
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|ClinicalTrials.gov Identifier: NCT03603509|
Recruitment Status : Active, not recruiting
First Posted : July 27, 2018
Last Update Posted : February 19, 2019
|Condition or disease||Intervention/treatment||Phase|
|Influenza||Drug: Fluad Vaccine Drug: Fluzone High-Dose||Phase 4|
The overall goal of this proposal is to determine how vaccine type, sex, and gene expression influence both innate and T helper cell immune responses using systems biology and bioinformatics as tools to comprehensively assess the human transcriptome. We will evaluate sex-dependent immune responses to two unique influenza vaccines in a population of older adults; the recently FDA-licensed MF59-adjuvanted influenza subunit vaccine and the high-dose split virion influenza virus vaccine. The influence of sex on immune response to vaccination has been observed across multiple vaccines (including standard dose influenza vaccines, but the mechanisms are unknown, it affects all age groups regardless of hormonal status, and existing studies focus almost exclusively on humoral immune responses. Relatively little is known about the effect of sex on innate and T helper responses following vaccination and we are unaware of any studies evaluating the effect of sex on immune responses to adjuvanted influenza vaccine. The presence of adjuvant (MF59Flu) or higher antigen (Ag) dose leads to greater immunogenicity through mechanisms that have not been fully deciphered and are likely to be different. Further, a direct com-arison of innate and T helper immune responses between adjuvanted and high dose influenza vaccines has not been reported.
The study design will include 200 generally healthy individuals (ages ≥65) who meet all inclusion criteria. 100 subjects will receive each vaccine with equal sex representation in each subgroup (a factorial design for sex by vaccine type). Subjects will undergo venipuncture for blood samples (~100 mL each, sufficient for the proposed assays) before vaccination and at three timepoints after vaccination (Day 1, Day 8, Day 28).
The clinical characterization of our study subjects will include demographic information, height, weight, BMI, waist circumference, medications, and medical conditions that do not meet exclusion criteria (see Protection of Human Subjects). We will also quantify blood leukocyte populations (CBC, WBC differential).
Immunosenescence and cytomegalovirus (CMV) infection can affect influenza vaccine-induced immune responses. We will evaluate whether CMV seropositivity or other measures of immunosenescence are associated with immune response and whether they interact with vaccine type/sex.
We will monitor/characterize transcriptional changes (mRNA and miRNA) as well as measures of immune function (cytokine secretion, leukocyte surface phenotype, hemagglutination inhibiting antibody titer, and memory B cell ELISPOT) at each time point.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||241 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||Eligible subjects who consent and enroll will be randomly assigned to receive either the Fluad Vaccine or Fluzone High-Dose vaccine.|
|Masking:||None (Open Label)|
|Primary Purpose:||Basic Science|
|Official Title:||Transcriptomic Signatures of Influenza Vaccine Responses|
|Actual Study Start Date :||August 27, 2018|
|Actual Primary Completion Date :||January 2, 2019|
|Estimated Study Completion Date :||February 23, 2022|
Active Comparator: Fluad vaccine
110 subjects will receive a single dose of the Fluad influenza vaccine.
Drug: Fluad Vaccine
110 subjects will be randomized to receive the high dose influenza vaccine, Fluad
Other Name: adjuvanted influenza vaccine
Active Comparator: Fluzone vaccine
110 subjects will receive a single dose of the Fluzone High-Dose influenza vaccine.
Drug: Fluzone High-Dose
110 subjects will be randomized to receive the high dose influenza vaccine, Fluzone High-Dose
Other Name: high dose influenza vaccine
- Innate cell cytokine production [ Time Frame: Baseline, Day 1, Day 7 ]cytokine secretion after in vitro stimulation with influenza virus
- Hemagglutination Ab titer [ Time Frame: Baseline, Day 1, Day 7, and Day 28 ]Serum titer of HAI antibody
- Memory B cell ELISPOT response [ Time Frame: Baseline, Day 7, and Day 28 ]Influenza-specific memory B cells
- Plasmablast ELISPOT response [ Time Frame: Baseline, Day 7, and Day 28 ]influenza-specific antibody secreting B cells
- B cell gene expression [ Time Frame: Baseline, Day 8, Day 28 ]Next generation sequencing of purified B cells' RNA
- B cell miRNA expression [ Time Frame: Baseline, Day 8, Day 28 ]Next generation sequencing of purified B cells' miRNA
- Innate cell gene expression [ Time Frame: Baseline, Day 1, Day 8 ]Next generation sequencing of purified B cells' RNANext generation Next generation sequencing of purified B cells' RNA
- Innate cell miRNA expression [ Time Frame: Baseline, Day 1, Day 8 ]Next generation sequencing of purified innate cells' miRNA
- B cell phenotype [ Time Frame: Baseline, Day 7, and Day 28 ]flow cytometry analysis of B cells
- Innate cell phenotype [ Time Frame: Baseline, Day 1, Day 8 ]flow cytometry analysis of innate cells
- CMV serostatus [ Time Frame: Baseline ]serum CMV-specific IgG/IgM titer
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03603509
|United States, Minnesota|
|Mayo Clinic in Rochester|
|Rochester, Minnesota, United States, 55905|
|Principal Investigator:||Richard B Kennedy||Mayo Clinic|