Study of Immune Responses in Healthy Adults Receiving Live Influenza Virus Vaccines
|ClinicalTrials.gov Identifier: NCT01674205|
Recruitment Status : Completed
First Posted : August 28, 2012
Last Update Posted : December 15, 2015
|Condition or disease||Intervention/treatment||Phase|
|Influenza, Human||Biological: A/swine/Missouri/4296424/2006 (H2N3) x A/Ann Arbor/6/60 ca (H2N3 MO 2006/AA ca) Biological: A/chicken/Hong Kong/G9/97 (H9N2) x A/Ann Arbor/6/60 ca (H9N2 G9/AA ca) Biological: 2012-2013 trivalent seasonal live attenuated influenza vaccine (FluMist®) Biological: Vaccine placebo (Leibovitz-15 [L-15]) Biological: Vaccine placebo (FluMist®)||Phase 1|
Influenza A viruses are widely distributed in nature and exist as many different subtypes. Pandemics of influenza can occur, and vaccine development is focused on those subtypes that are predicted to represent the greatest pandemic threat to the human population. This study seeks to understand the host factors that affect the replication and immune response of seasonal and candidate pandemic LAIVs in humans and to develop biomarkers that can predict the viral shedding and immune response to LAIVs.
Three vaccines will be evaluated: the licensed seasonal LAIV, with a focus on the H3N2 component; the H9N2 G9/AA ca vaccine, which is among the most immunogenic of the candidate pandemic LAIVs evaluated to date; and the H2N3 MO 2066/AA ca vaccine, which is among the least immunogenic of the candidate pandemic LAIVs evaluated to date. The seasonal LAIV will be evaluated in an outpatient setting, while the other two vaccines will be evaluated in an inpatient setting. In each setting, some participants will receive a placebo vaccine.
Study participants will be assigned to one of four groups. Participants who are seronegative to both H9N2 G9/AA ca and H2N3 MO 2006/AA ca viruses will be randomly assigned to receive one of those vaccines (Group 1: H9N2 G9/AA ca; Group 2: H2N3 MO 2006/AA ca) or placebo (Group 4) and will remain in an inpatient isolation facility. Participants who are seronegative to the H3 component of seasonal LAIV will be randomly assigned to receive either seasonal vaccine (Group 3) or placebo (Group 4) and will be followed as outpatients.
All participants will remain in the study for 56 days. Participants in the inpatient arms will be admitted on Day -2, will receive study vaccine on Day 0, and will undergo a basic history, physical examination, and nasal wash each day until discharge. On some study days, inpatient participants will undergo a blood collection and/or a nasal swab; at the screening visit and on Day -1 or Day -2, participants will give a urine sample.
Participants in the outpatient arms will receive study vaccine on Day 0 and will have study visits on Days 1, 2, 3, 4, 5, 6, 7, 14, 28, and 56. On Days 1 through 7, participants will undergo a basic history, physical examination, and nasal wash. On some visits, participants may undergo a blood collection and/or a nasal swab; at the screening visit and on Day -1, participants will give a urine sample. Unused blood or nasal wash samples will be stored and may be used in future research studies.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||36 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Triple (Participant, Care Provider, Investigator)|
|Primary Purpose:||Basic Science|
|Official Title:||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)|
|Study Start Date :||September 2012|
|Actual Primary Completion Date :||June 2013|
|Actual Study Completion Date :||June 2013|
Experimental: Group 1 (Inpatient, H2N3 MO 2006/AA ca)
Participants will receive one dose of vaccine on Day 0, with 0.2 mL being delivered by Accuspray device (0.1 mL per nostril).
|Biological: A/swine/Missouri/4296424/2006 (H2N3) x A/Ann Arbor/6/60 ca (H2N3 MO 2006/AA ca)|
Experimental: Group 2 (Inpatient, H9N2 G9/AA ca)
Participants 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.
|Biological: A/chicken/Hong Kong/G9/97 (H9N2) x A/Ann Arbor/6/60 ca (H9N2 G9/AA ca)|
Experimental: Group 3 (Outpatient, seasonal LAIV [FluMist®])
2012-2013 trivalent seasonal live attenuated influenza vaccine (FluMist®)
|Biological: 2012-2013 trivalent seasonal live attenuated influenza vaccine (FluMist®)|
Placebo Comparator: Group 4 (Both inpatient and outpatient, placebo)
Participants will receive either the L-15 placebo delivered by nose drops or the FluMist® placebo delivered as a nasal spray.
|Biological: Vaccine placebo (Leibovitz-15 [L-15]) Biological: Vaccine placebo (FluMist®)|
- 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 [ Time Frame: Measured through Day 9 ]
- Development of serum antibody as assessed by either HAI or microneutralization (MN) assays [ Time Frame: Measured through Day 56 ]
- Development of a significant increase in nasal secretion hemagglutinin (HA)-specific antibody assessed by enzyme-linked immunosorbent assay (ELISA) [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: Measured at Day 28 ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01674205
|United States, New York|
|University of Rochester Medical Center: Facility for Evaluation of Flu Vaccines|
|Rochester, New York, United States, 14642|
|Principal Investigator:||John Treanor, MD||University of Rochester|