The Impact of Imprinting and Repeated Influenza Vaccination on Adaptive Immunity, Transcriptomics, and Metabolomics

NCT03686514 | Terminated Phase 4 Results DMC FDA Drug

• 1 other identifier: IRB00106407
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this study is to understand the impact on the human immune system's response to the four strain flu vaccine in individuals who have "imprinted" on specific influenza strains. It will also consider the effects of repeated prior annual influenza vaccination on the immune system.

Conditions

Influenza

Keywords

Flu vaccine; Influenza vaccine; Immune response; Influenza strain

Outcome Measures

Primary Outcomes (3)

• The Number of Participants Achieving Seroprotection Against Each Strain

  Seroprotection against each strain contained in the seasonal quadrivalent influenza vaccine (A/H1N1, A/H3N2, B/Phuket, and B/Colorado) were measured by hemagglutination inhibition (HAI) antibody response. Seroprotection is defined as a titer of ≥ 40.

  28 days after vaccination

• The Number of Participants Achieving Seroconversion Against Each Strain

  Seroconversion against each strain contained in the seasonal quadrivalent influenza vaccine was measured by HAI antibody response. Seroconversion is defined as a four-fold rise in HAI post- compared to pre-vaccination, or a titer of ≥40 if the pre-vaccination titer was \<10.

  28 days after vaccination

• Geometric Mean Titers (GMTs) of Serum HAI Against Each Strain

  The geometric scale is logarithmic. A geometric mean is calculated by averaging the logarithms of the test values and then converting the mean to a real number.

  28 days after vaccination

Secondary Outcomes (7)

• The Proportion of Participants Achieving Seroprotection or Seroconversion Against Each Strain Measured by Neutralizing Antibody (NAb) Response

  28 days after vaccination

• Geometric Mean Titers (GMTs) of Serum NAb Against Each Strain

  28 days after vaccination

• The Number of Participants Achieving Seroprotection Against Each Strain

  180 days after vaccination

• The Number of Participants Achieving Seroconversion Against Each Strain

  180 days after vaccination

• Geometric Mean Titers (GMTs) of Serum HAI Against Each Strain

  180 days after vaccination

Study Arms (2)

H3N2 birth cohort

EXPERIMENTAL

The H3N2 cohort consists of participants born between 1968-1977.

Biological: FLUARIX QUADRIVALENT

H1N1 birth cohort

EXPERIMENTAL

The H1N1 cohort consists of participants born between 1948-1957.

Biological: FLUARIX QUADRIVALENT

Interventions

FLUARIX QUADRIVALENT BIOLOGICAL

The FDA-approved, quadrivalent seasonal influenza vaccine that will be administered contains four distinct strains, two influenza A viruses and two influenza B viruses.

H1N1 birth cohort; H3N2 birth cohort

Eligibility Criteria

• Age: 42 Years - 71 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Capable of informed consent and provision of written informed consent before any study procedures.
• Capable of attending all study visits according to the study schedule.
• Males or females born between 1968-1977 or 1948-1957.
• Are in good health, as determined by medical history and targeted physical exam related to this history.
• Oral temperature is less than 38 degrees Celsius.
• Resting pulse rate is between 50 and 100 beats per minute.
• Female subjects of childbearing age must have a negative urine pregnancy test within 24 hours before study vaccination.
• Have received the influenza vaccine at least 3 of the past 5 years or have received the influenza vaccine in 2 or less of the past 5 years.

You may not qualify if:

• Have an acute illness within 72 hours before vaccination.
• Have any condition that, in the opinion of the principal investigator, would place the subject at an unacceptable risk of harm or confound the interpretation of the study results.
• Have any acute or chronic medical condition that, in the opinion of the principal investigator, would make vaccination unsafe or interfere with the evaluation of immune response to study vaccination.
• Have a suppressed immune system as a result of illness, immunosuppressive medication, chemotherapy, or radiation therapy within 3 years prior to study vaccination.
• Have known HIV, hepatitis B, or hepatitis C infection.
• Have a known history of autoimmune disease.
• Have taken oral or parenteral corticosteroids of any dose within 30 days before study vaccination.
• Have taken high-dose inhaled corticosteroids within 30 days before study vaccination.
• Have received, or plan to receive, any licensed live vaccine within 30 days, or any licensed inactivated vaccine within 14 days, prior to, or after, study vaccination.
• Have planned receipt of any unlicensed or investigational medications, biologics, or vaccines for the duration of subject study participation.
• Have received immunoglobulin or other blood products, with the exception of Rho D immunoglobulin, within 90 days prior to study vaccination.
• Have donated blood or blood products within 30 days before study vaccination, or within 60 days after study vaccination, or plan to donate blood within 30 days of the last blood draw.
• Have known hypersensitivity or allergy to eggs, egg protein, chicken protein, or other compounds of the study vaccine.
• Have a history of severe reactions following vaccination with influenza virus vaccines.

Sponsors & Collaborators

• Emory University: lead

Study Sites (1)

The Hope Clinic of the Emory Vaccine Center

Atlanta, Georgia, 30317, United States

Location

Related Publications (1)

• Sherman AC, Lai L, Bower M, Natrajan MS, Huerta C, Karmali V, Kleinhenz J, Xu Y, Rouphael N, Mulligan MJ. The Effects of Imprinting and Repeated Seasonal Influenza Vaccination on Adaptive Immunity after Influenza Vaccination. Vaccines (Basel). 2020 Nov 7;8(4):663. doi: 10.3390/vaccines8040663.

  PMID: 33171854 RESULT

MeSH Terms

Conditions

Influenza, Human

Condition Hierarchy (Ancestors)

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

Limitations and Caveats

Due to the COVID-19 pandemic, this study was terminated prior to beginning year 3 of the study.

Results Point of Contact

• Title: Nadine Rouphael, MD
• Organization: Emory University

nroupha@emory.edu

404-712-1435

Study Officials

• Nadine Rouphael, MD

  Emory University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: September 25, 2018
• First Posted: September 27, 2018
• Study Start: October 22, 2018
• Primary Completion: June 20, 2020
• Study Completion: June 20, 2020
• Last Updated: July 13, 2022
• Results First Posted: July 13, 2022

Record last verified: 2022-06

Locations

US (1)