Study of Immune Responses in Healthy Adults Receiving Live Influenza Virus Vaccines
Exploratory Evaluation of Host Biomarkers That Predict the Vaccine Virus Replication and Immunogenicity of Seasonal and Pandemic Formulations of Live Attenuated Influenza A Virus Vaccines Based on the A/Ann Arbor/6/60 ca Master Donor Virus (MDV)
1 other identifier
interventional
36
1 country
1
Brief Summary
This study seeks to understand the host factors that affect the replication and immune response of seasonal and candidate pandemic live attenuated influenza vaccine (LAIV) in humans and to develop biomarkers that can predict the viral shedding and immune response to LAIVs.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Sep 2012
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 23, 2012
CompletedFirst Posted
Study publicly available on registry
August 28, 2012
CompletedStudy Start
First participant enrolled
September 1, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 1, 2013
CompletedStudy Completion
Last participant's last visit for all outcomes
June 1, 2013
CompletedDecember 15, 2015
October 1, 2015
9 months
August 23, 2012
December 14, 2015
Conditions
Outcome Measures
Primary Outcomes (2)
Area under the curve (AUC) of nasal virus shedding after vaccine dose as assessed by liquid titration of nasal secretions on Madin Darby Canine Kidney (MDCK) cells
Measured through Day 9
Development of serum antibody as assessed by either HAI or microneutralization (MN) assays
Measured through Day 56
Secondary Outcomes (3)
Development of a significant increase in nasal secretion hemagglutinin (HA)-specific antibody assessed by enzyme-linked immunosorbent assay (ELISA)
Measured through Day 56
Detection of influenza-specific immunoglobulin G (IgG) or immunoglobulin A (IgA) secreting B cells assessed by antibody secreting cells (ASC) assay
Measured at Day 7
Development of greater than 200 influenza-specific interferon-gamma-secreting cells per million lymphocytes as assessed by enzyme-linked immunospot assay (ELISPOT)
Measured at Day 28
Study Arms (4)
Group 1 (Inpatient, H2N3 MO 2006/AA ca)
EXPERIMENTALParticipants will receive one dose of vaccine on Day 0, with 0.2 mL being delivered by Accuspray device (0.1 mL per nostril).
Group 2 (Inpatient, H9N2 G9/AA ca)
EXPERIMENTALParticipants will receive one dose of vaccine on Day 0, with 0.5 mL being delivered as nose drops (0.25 mL per nostril) using a sterile, needle-less tuberculin syringe.
Group 3 (Outpatient, seasonal LAIV [FluMist®])
EXPERIMENTAL2012-2013 trivalent seasonal live attenuated influenza vaccine (FluMist®)
Group 4 (Both inpatient and outpatient, placebo)
PLACEBO COMPARATORParticipants will receive either the L-15 placebo delivered by nose drops or the FluMist® placebo delivered as a nasal spray.
Interventions
Eligibility Criteria
You may qualify if:
- General good health, without significant medical illness, physical examination findings, or significant laboratory abnormalities as determined by the investigator
- Agree to storage of blood specimens for future research
- Available for the duration of the trial. For the inpatient component of the study, participants must be willing and able to remain within the Isolation Unit for the specified duration of confinement. For the outpatient component of the study, participants must be willing and able to make daily outpatient follow-up visits as specified by the protocol.
- Willingness to participate in the study as evidenced by signing the informed consent document
- Female participants must agree to use effective birth control methods for the duration of the study (for example, pharmacologic contraceptives including oral, parenteral, and transcutaneous delivery; condoms with spermicide; diaphragm with spermicide; intrauterine device; abstinence from heterosexual intercourse; or surgical sterilization). All female participants will be considered being of child-bearing potential except those who have undergone hysterectomy and those in whom menopause occurred at least 1 year prior to the study.
You may not qualify if:
- Pregnancy as determined by a positive human choriogonadotropin (beta-HCG) test
- Currently breastfeeding
- Behavioral or cognitive impairment or psychiatric disease that in the opinion of the investigator affects the ability of the subject to understand and cooperate with the study protocol
- Previous enrollment in an H2 or H9 influenza vaccine trial or in any study of an avian influenza vaccine
- For the inpatient arm, seropositive to the H2N3 influenza A virus or the H9N2 influenza A virus (serum HAI titer \>1:8). For the outpatient arm, seropositive to the H3N2 component of seasonal LAIV (serum hemagglutination inhibition \[HAI\] titer greater than 1:8).
- Positive urine drug toxicology test indicating narcotic use/dependency
- Have medical, occupational, or family problems as a result of alcohol or illicit drug use during the past 12 months
- Other condition that in the opinion of the investigator would jeopardize the safety or rights of a participant participating in the trial or would render the subject unable to comply with the protocol
- History of anaphylaxis
- Allergy to oseltamivir as determined by subject report
- Current diagnosis of asthma or reactive airway disease (within the past 2 years)
- History of Guillain-Barré Syndrome
- Positive ELISA and confirmatory Western blot tests for human immunodeficiency virus-1 (HIV-1)
- Positive ELISA and confirmatory test (e.g., recombinant immunoblot assay) for hepatitis C virus (HCV)
- Positive hepatitis B virus surface antigen (HBsAg) by ELISA
- +13 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
University of Rochester Medical Center: Facility for Evaluation of Flu Vaccines
Rochester, New York, 14642, United States
Related Publications (2)
Karron RA, Callahan K, Luke C, Thumar B, McAuliffe J, Schappell E, Joseph T, Coelingh K, Jin H, Kemble G, Murphy BR, Subbarao K. A live attenuated H9N2 influenza vaccine is well tolerated and immunogenic in healthy adults. J Infect Dis. 2009 Mar 1;199(5):711-6. doi: 10.1086/596558.
PMID: 19210163BACKGROUNDBelshe RB. Current status of live attenuated influenza virus vaccine in the US. Virus Res. 2004 Jul;103(1-2):177-85. doi: 10.1016/j.virusres.2004.02.031.
PMID: 15163507BACKGROUND
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
John Treanor, MD
University of Rochester
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR
- Purpose
- BASIC SCIENCE
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 23, 2012
First Posted
August 28, 2012
Study Start
September 1, 2012
Primary Completion
June 1, 2013
Study Completion
June 1, 2013
Last Updated
December 15, 2015
Record last verified: 2015-10