Gene Signatures of Influenza Vaccine Responses in Older Adults

NCT03603509 | Completed Phase 4 Results FDA Drug

• 2 other identifiers: 17-010601R01AI132348
• Study Type: interventional
• Target: 241
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this research study is to better understand the immune response to the Adjuvanted Subunit flu vaccine (MF59) and the High Dose flu vaccine (HDFlu) in people 65 years of age and older. The research team will be studying why immune response diminishes as people get older in both men and women. The ultimate goal is to understand how flu immunity develops after vaccination. This information may lead to the development of more effective flu vaccines in the future.

Conditions

Influenza

Keywords

Fluad, MF59, Fluzone, HDFlu, Influenza, Vaccine

Outcome Measures

Primary Outcomes (7)

• Innate Cell IFNa2a Production

  Cytokine secretion (interferon alpha 2a) after in vitro stimulation with influenza virus

  Baseline, Day 1

• Hemagglutination Inhibition Ab Titer

  Reciprocal of the serum dilution exhibiting no hemagglutination (the larger the number, the more agglutinating antibodies the subject has. A titer of equal to more than 1:40 and above is considered a protective antibody titer)

  Baseline and Day 28

• T Cell Gene Expression

  Gene expression counts. The number shown is the total number of RNA molecules whose sequence matches a human gene. This is a measure of how much gene expression is occurring in the cells in each subject's blood sample.

  Baseline, Day 28

• T Cell miRNA Expression

  Next generation sequencing of purified T cells' miRNA

  Baseline, Day 8, Day 28

• Innate IFNAR1 Cell Gene Expression

  IFNAR1 gene counts (the number of molecules of RNA whose sequence matches the interferon alpha receptor 1 gene that were present in the subject's blood sample).

  Baseline, Day 8

• Innate Cell miRNA Expression

  Next generation sequencing of purified innate cells' miRNA

  Baseline, Day 1, Day 8

• Memory B Cell ELISPOT

  Number of influenza-specific Ab producing memory B cells. Spot Forming Units (SFUs) are the frequency of Ab secreting B cells in an ELISPOT assay.

  Day 28

Secondary Outcomes (5)

• T Cell ELISPOT Response

  Day 28

• T Cell Phenotype

  Day 28

• Innate Cell Phenotype

  Day 1 (stim)

• CMV Serostatus

  Baseline

• CD4/CD8 Ratio

  Day 28

Study Arms (2)

Fluad vaccine

ACTIVE COMPARATOR

Subjects receive a single dose of the Fluad influenza vaccine.

Drug: Fluad Vaccine

Fluzone vaccine

ACTIVE COMPARATOR

Subjects receive a single dose of the Fluzone High-Dose influenza vaccine.

Drug: Fluzone High-Dose

Interventions

Fluad Vaccine DRUG

FLUAD is an inactivated influenza vaccine indicated for active immunization against influenza. disease caused by influenza virus subtypes A and type B contained in the vaccine. FLUAD is. approved for use in persons 65 years of age and older.

Also known as: adjuvanted influenza vaccine

Fluad vaccine

Fluzone High-Dose DRUG

FLUZONE® HIGH-DOSE vaccine is indicated for people 65 years of age and older to help prevent influenza disease caused by influenza A and B strains contained in the vaccine.

Also known as: high dose influenza vaccine

Fluzone vaccine

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Older Adult (65+)

You may qualify if:

• Male or female adults ages 18-40 or of 65 and or older at the time of enrollment
• Eligible to receive Fluad® (MF59Flu) or Fluzone® (HDFlu) if age 65 or older
• No history of anaphylactic reaction to gelatin, neomycin, or other vaccine component
• Not pregnant
• No immunosuppression or immunodeficiency
• No acute illness at time of vaccination
• Determined by medical history and clinical judgment to be eligible for the study, by being generally healthy, with no autoimmune or immunosuppressive conditions and having stable current medical conditions (subjects with preexisting stable disease, defined as disease not requiring significant change in therapy or hospitalization for worsening disease 12 weeks before receipt of study vaccine, will be eligible. A change in dose or therapy within a category (e.g., change from one nonsteroidal anti-inflammatory drug to another) is allowed. A change to a new therapy category (e.g., surgery or addition of a new pharmacological class) is only allowed if it is not caused by worsening disease. A change to a new therapy category caused by worsening disease is considered significant and therefore ineligible for enrollment.
• Able to follow study procedures in the opinion of the investigator
• Expected to be available for the duration of the study
• Weighs \>110 lbs

You may not qualify if:

• Known or suspected immunodeficiency or receiving treatment with immunosuppressive therapy including cytotoxic agents or systemic corticosteroids (e.g., for cancer, HIV, or autoimmune disease). If systemic corticosteroids have been administered short term for treatment of an acute illness, subjects will be included if corticosteroid therapy (inhaled, intranasal, and intra-articular corticosteroid therapy is permitted) has been discontinued for at least 30 days.
• Serious chronic medical conditions including metastatic malignancy, severe chronic obstructive pulmonary disease requiring supplemental oxygen, end-stage renal disease with or without dialysis, clinically unstable cardiac disease, or any other disorder that, in the investigator's opinion, precludes the subject from participating in the study. Diabetic patients will be excluded if they do not have a hemoglobin A1c measurement within the past 6 months or if they had a hemoglobin A1c measurement of an A1c \>8.0
• Receipt of any blood products, including immunoglobulin, within 6 months of study enrollment.
• Current anticoagulant therapy or a history of bleeding diathesis that would contraindicate intramuscular (IM) injection. (Note: antiplatelet drugs such as aspirin and clopidogrel are permitted.)
• Receipt of any vaccines within the past 30 days prior to enrollment
• Receipt of the current seasonal influenza vaccine other than in this study
• Acute illness within the last 30 days
• Blood donation within the last 58 days prior to study enrollment
• Any medical condition that would, in the opinion of the investigator, interfere with the evaluation of the study objectives
• Pregnant patients will be excluded
• Any condition (e.g. allergic reaction, Guillain-Barre Syndrome) that precludes their receipt of the influenza vaccine

Sponsors & Collaborators

• Mayo Clinic: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (1)

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Influenza, Human

Interventions

fluad vaccine; Fluzone High-Dose; Influenza Vaccines

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Viral Vaccines; Vaccines; Biological Products; Complex Mixtures

Results Point of Contact

• Title: Richard Kennedy, PhD
• Organization: Mayo Clinic

Kennedy.Rick@mayo.edu

507-284-0708

Study Officials

• Richard B Kennedy

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Eligible subjects who consent and enroll will be randomly assigned to receive either the Fluad Vaccine or Fluzone High-Dose vaccine.

Study Record Dates

• First Submitted: July 18, 2018
• First Posted: July 27, 2018
• Study Start: August 27, 2018
• Primary Completion: January 2, 2019
• Study Completion: January 2, 2019
• Last Updated: May 16, 2023
• Results First Posted: May 16, 2023

Record last verified: 2023-04

Locations

US (1)