The Immunologic Basis for an Attenuated Immune Response to the Influenza Vaccine After Repeated Annual Vaccination (FLU1)

This is a prospective pilot study designed to suggest differences in the immunologic response to the seasonal influenza vaccine in people with regular vaccination history compared to those vaccinated less regularly. Participants will receive one dose of the Food and Drug Administration (FDA) approved 2016-2017 seasonal influenza vaccine. Immune system data will be collected at standard time points. The duration of the study for each participant will be approximately 1 month.

Study Overview

• Status: Completed
• Conditions: Influenza
• Intervention / Treatment: Biological: 2016-2017 Influenza Vaccine

Detailed Description

This is a prospective pilot study in 20 males and non-pregnant females, 20 to 30 years old, inclusive, who are in good health and meet all eligibility criteria. The study is designed to evaluate differences in the immunologic response to the seasonal influenza vaccine in people with regular vaccination history compared to those vaccinated less regularly.

Participants will be sorted to either Arm A (Naïve) or Arm B (Experienced) based on their vaccination history. Those vaccinated no more than 2 out of the past 5 years will be in Arm A. Those vaccinated 3 or more out of the past 5 years will be in Arm B. Participants will receive one dose of the Food and Drug Administration (FDA) approved 2016-2017 seasonal influenza vaccine. The duration of the study for each participant will be approximately 1 month. Subjects will return for clinic visits on Days 3, 8, 15, and 29 during the month follow-up period following vaccination.

The study has two primary objectives; to evaluate the antibody response to the influenza vaccine in people who are vaccinated regularly and those vaccinated less regularly; the second is to evaluate circulating follicular helper T cells (TFH) in people who are vaccinated regularly and those vaccinated less regularly.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • The Hope Clinic of the Emory Vaccine Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 30 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 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.
• 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 115 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.

Exclusion Criteria:

• 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 injury 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 any licensed live vaccine within 30 days or any licensed inactivated vaccine within 14 days prior to study vaccination.
• Have planned vaccination with any vaccine during the 29-day 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, plan to donate blood at any time during the 29-day duration of subject study participation, or plan to donate blood within 30 days after 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vaccination Naïve; Participants who have received an influenza vaccine in 2 or less of the past 5 years will receive the FDA-approved 2016-2017 influenza vaccine.	Biological: 2016-2017 Influenza Vaccine; Quadrivalent influenza A/Hemagglutinin Type 1 (H1N1), A/Influenza A virus subtype (A/H3N2) H3N2,and B virus vaccine for Intramuscular (IM) use is a sterile, clear and slightly opalescent suspension administered as a single 0.5 mL intramuscular dose.
Experimental: Vaccination Experienced; Participants who have received an influenza vaccine at least 3 of the past 5 years will receive the FDA-approved 2016-2017 influenza vaccine.	Biological: 2016-2017 Influenza Vaccine; Quadrivalent influenza A/Hemagglutinin Type 1 (H1N1), A/Influenza A virus subtype (A/H3N2) H3N2,and B virus vaccine for Intramuscular (IM) use is a sterile, clear and slightly opalescent suspension administered as a single 0.5 mL intramuscular dose.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Geometric Mean Serum Hemagglutination Inhibition (HAI) Antibody Titer	Geometric mean serum HAI antibody titers serum HAI titer will be collected via blood draw. Titer for serum HAI antibodies will be calculated using the geometric mean. Change is defined as the difference in means from Day 1 to Day 29.	Baseline (Day 1), Day 29
Change in Mean Level of Circulating Follicular Helper T (TFH) Cells	TFH cells will be collected via blood draw. Change is defined as the difference in the mean levels of cells from baseline, day 8, and day 15.	Up to 15 Days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Mean Levels of Plasmablasts	Plasmablasts will be collected via blood draw. Change is defined as the difference in mean levels from baseline to Day 29.	Up to 29 Days
Change in Mean Levels of Memory B Cells From Baseline (Day 1) to Day 29	Memory B cells will be collected via blood draw. Change is defined as the difference in mean levels from baseline to Day 29.	Baseline (Day 1) and Day 29
Change in Mean Levels of Antigen-specific IL-2 Producing CD4+ T Cells	Antigen-specific Interleukin 2 (IL-2) producing cluster of differentiation 4 (CD4)+ T cells will be collected via blood draw. Change is defined as the difference in mean levels from baseline to Day 29.	Up to 29 Days
Change in Mean Levels of Antigen-specific Cluster of Differentiation 8 (CD8) + T Cells	CD8+T cells will be collected via blood draw. Change is defined as the difference in mean levels from baseline to Day 29.	Up to 29 Days

Collaborators and Investigators

• Sponsor: Emory University
• Investigators: Principal Investigator: Mark Mulligan, MD, Emory University

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2016
• Primary Completion (Actual): October 18, 2016
• Study Completion (Actual): December 1, 2016

Study Registration Dates

• First Submitted: August 4, 2016
• First Submitted That Met QC Criteria: August 18, 2016
• First Posted (Estimate): August 23, 2016

Study Record Updates

• Last Update Posted (Actual): December 12, 2018
• Last Update Submitted That Met QC Criteria: December 11, 2018
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Keywords: Vaccination
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human
• Other Study ID Numbers: IRB00090196