Clinical trial NCT02597647: Bacterial Composition and Immune Responses in the Nose and Oropharynx During Influenza Infection
Official title: Bacterial Composition and Immune Responses in the Nose and Oropharynx During Influenza Infection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Influenza
Keywords: immunology
Microbiota
Lead sponsor: University of California, Los Angeles
Sponsor class: OTHER
Collaborators: name: J. Craig Venter Institute
First posted: 2015-11-05
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: This study will serve to determine how influenza infection alters the bacterial colonization patterns in the nasal and oropharyngeal compartments, and whether the immune response correlate with these alterations. The investigators will be determining bacterial composition and immune responses in the nose and oropharynx during influenza infection.

Specific Aims

Therefore, the overall aims of this study are as follows:

1. To identify baseline composition and kinetic changes in the nasal and oropharyngeal microflora and immune responses after administering intranasal live attenuated influenza virus (i.e., FluMist® vaccine) or saline mist to healthy subjects;
2. To identify nasal and oropharyngeal microbial composition and local immune responses during influenza infections and after resolution of infection, and correlate these changes with clinical outcomes.

Detailed description: Randomization and Post-Randomization Visits After undergoing the nasal swabs and nasopharyngeal washes, and nasal epithelial brushing, healthy volunteers will be randomly assigned to receive either saline nasal spray (placebo) or FluMist® nasal influenza vaccine (live attenuated influenza vaccine, or LAIV). They will return 1-2 weeks and 4-6 weeks later to repeat the nasal swabs and nasopharyngeal washes, and nasal epithelial brushings done at the Enrollment Visit.

Samples will be processed to isolate 16s bacterial RNA and host RNA. 16s rRNA will be analyzed by 16S sequencing for to determine the composition of the bacterial microbiome pre and post LAIV or saline (placebo) administration. Host immune responses will be assessed based upon microarray analysis of host RNA pre and post LAIV or saline administration.

Eligibility criteria: Inclusion Criteria:

* Healthy volunteers:
* Healthy subjects between the ages of 18 and 65. Approximately half of the subjects will be female and approximately half will be male.
* Must be eligible to receive live-attenuated nasal version of the influenza vaccine.
* Must be able to provide signed and dated informed consent.
* Healthy subjects willing and able to provide oropharyngeal and nasal cavity specimens

Exclusion Criteria:

* Immunosuppressive conditions or medications
* chronic systemic medical illness
* infections or antibiotic use within the past 60 days

Primary outcomes:
measure: Changes in the bacterial composition (Bacterial "microbiome") over time
timeFrame: Changes from baseline at 1-2 weeks and 4-6 weeks after LAIV or saline spray
measure: Changes in gene expression in the nasal lining of study participants
timeFrame: Changes from baseline at 1-2 weeks after LAIV or saline spray
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA
state: California
Study officials:
References:
citation: Tarabichi Y, Li K, Hu S, Nguyen C, Wang X, Elashoff D, Saira K, Frank B, Bihan M, Ghedin E, Methe BA, Deng JC. The administration of intranasal live attenuated influenza vaccine induces changes in the nasal microbiota and nasal epithelium gene expression profiles. Microbiome. 2015 Dec 15;3:74. doi: 10.1186/s40168-015-0133-2.