Strategies for Enhancing Mucosal Immunity to Influenza Vaccine

The purpose of this study is to determine the safety and effectiveness of the influenza vaccine when administered nasally and intra-muscular (a "shot" of medicine given into a muscle). The investigators will measure the systemic (through out the body) and mucosal immune responses (how your body recognizes and defends itself against bacteria) to nasally administered influenza vaccine, and determine if nasal immunization results in immunity (your body's ability to avoid infections) within multiple mucosal compartments (ocular (eye), oral and reproductive), in comparison with intramuscular administration and placebo (inactive substance given in the same form as the active drug).

Study Overview

• Status: Completed
• Conditions: Mucosal Immunity
• Intervention / Treatment: Drug: Fluzone; Drug: Fluzone

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy men and women ages 18-50 years
• Non-smokers (defined as no tobacco use within the last 12 months and less than 10 pack-year lifetime tobacco use)
• Willing and able to provide written informed consent
• Able to speak and understand English
• Women of childbearing potential must have a negative serum pregnancy test.

Exclusion Criteria:

• Influenza vaccination within 6 months prior to screening date
• Symptoms of respiratory infection during the 14 days prior to screening
• Temperature >38.3o C during the period spanning 72 hours prior to screening and the time of immunization.
• History of allergy to egg, influenza vaccine or vaccine ingredients
• History of Guillain-Barre syndrome
• History of Bell's palsy
• Tonsillectomy, adenoidectomy or prior surgery to the paranasal sinus cavity.
• Physician diagnosis of or personal history of allergic or chronic rhinitis
• Physician diagnosis of or personal history of asthma
• Acute sinusitis within 30 days prior to screening
• Use of antibiotics within 14 days prior to screening
• Requirement for use of nasal corticosteroids for the period beginning 30 days prior to screening through final study visit
• Requirement for use of antihistamines (systemic, intranasal or intraocular) for the period beginning 72 hours prior to screening through final study visit
• Use of immunomodulating drugs or systemic corticosteroids within 6 months prior to screening (includes but is not limited to azathioprine, methotrexate, mycophenolate mofetil, tumor necrosis factor inhibitors, cyclosporine, tacrolimus)
• Past or present history of allergen immunotherapy to within the last 10 years.
• Students or employees who are under direct supervision by any of the investigators in this protocol are not eligible to participate.
• Subjects who abuse alcohol or illicit substances will be excluded.
• Other medical or psychological conditions which, in the opinion of the investigator, might create undue risk to the subject or interfere with the subject's ability to comply with the protocol requirements.
• Nursing mothers.
• Other investigational medication use within 30 days of screening.

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Fluzone; 0.5 ml/15 micrograms; Drug: Fluzone; 0.5 ml/60 micrograms
Placebo Comparator: Nasal Aerosol Immunization	Drug: Fluzone; 0.5 ml/15 micrograms; Drug: Fluzone; 0.5 ml/60 micrograms
Placebo Comparator: Nasal Droplet Immunization	Drug: Fluzone; 0.5 ml/15 micrograms; Drug: Fluzone; 0.5 ml/60 micrograms
Placebo Comparator: Intramuscular Immunization	Drug: Fluzone; 0.5 ml/15 micrograms; Drug: Fluzone; 0.5 ml/60 micrograms

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in hemagglutinin antibody titers from baseline to Day 28 in serum and mucosal secretions.	Assessments will include hemagglutination inhibition and antibody isotypes determination.	Baseline to Day 28

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of subjects with adverse events.	Baseline to Day 28
Comparison of hemagglutinin antibody titers between intranasal and intramuscular route of administration, from baseline to Day 28.	Baseline to Day 28

Collaborators and Investigators

• Sponsor: John Sundy
• Investigators: Principal Investigator: John Sundy, MD, PhD, Duke University

Study record dates

Study Major Dates

• Study Start: April 1, 2011
• Primary Completion (Actual): June 1, 2011
• Study Completion (Actual): June 1, 2011

Study Registration Dates

• First Submitted: April 25, 2011
• First Submitted That Met QC Criteria: June 29, 2011
• First Posted (Estimate): June 30, 2011

Study Record Updates

• Last Update Posted (Estimate): December 6, 2012
• Last Update Submitted That Met QC Criteria: December 5, 2012
• Last Verified: December 1, 2012

More Information

Terms related to this study

• Keywords: Vaccination; Mucosal Immunity; Nasal Immunization
• Other Study ID Numbers: Pro00024277