Studying Cell Immune Responses to a Live Flu Vaccine in Healthy Adults
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|ClinicalTrials.gov Identifier: NCT01730144|
Recruitment Status : Completed
First Posted : November 21, 2012
Last Update Posted : June 20, 2018
- One form of the influenza vaccine is a nasal spray. It uses a live but weakened flu virus. Researchers want to better under how the live vaccine interacts with the body s immune system. They will test the nasal spray flu vaccine (called FluMist) against a saline (salt water) nasal spray. They will then look at blood and nasal cell samples to see how the vaccine affects these cells immune response.
- To look at immune changes in nasal and blood cells in people who receive live flu vaccine.
- Healthy volunteers between 18 and 49 years of age.
- Participants will have five outpatient visits for this study. Each visit will last up to 2 hours.
- At the first visit, participants will have a physical exam and medical history. They will give blood and urine samples. Nasal cell samples will also be collected.
- A week later, participants will have either the nasal spray flu vaccine or a saline spray. They will know which spray they will receive. Blood samples will be collected.
- Two days after the vaccination, they will have another physical exam. Blood and nasal cell samples will be collected.
- At the final two visits (1 week and 1 month after the vaccination), more blood samples will be collected.
- Those who had the saline spray will be able to have the actual vaccine spray at the last study visit.
- The ratio of participants who receive vaccine to those who receive saline will be 4:1.
|Condition or disease|
Two types of influenza vaccines are currently licensed in the US, trivalent inactivated vaccine (TIV), administered by intramuscular injection, and LAIV, administered by nasal spray. Both vaccines are safe and effective in their approved age groups. Neutralizing antibody in the serum has been found to be a correlate of protection for TIV, but the immune correlates of protection for LAIV are not known. Defining the origin and nature of transcriptional responses to LAIV in URT in infected and bystander epithelial and lymphocyte cells in healthy adults will be a highly informative first step in a systems approach toward understanding the molecular basis of viral replication restriction and the regulation of the local mucosal immune responses following LAIV administration.
This natural history study will use a systems biology approach to identify LAIV replication niches among a variety of URT cell types and characterize the host immune response to LAIV. Healthy volunteers aged 18-49 years will be prescreened for low (<1:10) serum HAI titer against the component influenza vaccine virus strains (influenza A H1N1 and H3N2, and influenza B) of the licensed seasonal LAIV. Ten HAIlow or -negative individuals will be vaccinated intranasally with LAIV (n=8) or will receive saline intranasally (n=2). One week prior to and 2 days after vaccine administration, an NP specimen will be collected using flocked NP swabs. A blood sample will be collected at the time of NP swabbing and on Days 7 and 28 after vaccination. Total subject participation time from enrollment/baseline to the final study visit will be 5 weeks.
We propose to recover cells from NP swab samples and sort individual cells of different subsets based on specific surface phenotypic markers. We will then utilize microfluidics-based real-time reverse transcriptase polymerase chain reaction (rRT-PCR) to quantify transcripts from bulk and single cells. These transcripts will include strand-specific influenza RNA for determining virus replication, genes for assigning cells to specific epithelial or lymphocyte subpopulations, selected genes in the IFN signaling pathways to determine innate immune responses, and genes involved in activation and effector functions of different immune cell subsets. Results will be analyzed with several bioinformatics tools, with an emphasis on the differential signaling responses between various cells types. The mucosal transcriptional data will be correlated with B and T cell immunity markers and traditional serology (HAI and neutralization assays) before and after vaccination to identify key factors affecting the immune response to LAIV.
|Study Type :||Observational|
|Actual Enrollment :||10 participants|
|Official Title:||Elucidation of the Mucosal Immune Responses to Live Attenuated Influenza Vaccine In Healthy Adults|
|Study Start Date :||November 17, 2012|
|Actual Primary Completion Date :||April 17, 2013|
|Actual Study Completion Date :||October 7, 2013|
- Significant differences in transcription of selected genes in nasal mucosal epithelial and immune cells isolated from recipients of LAIV compared to pre-vaccination levels in the same cell populations isolated. [ Time Frame: One week prior to and 2 days after vaccine administration and on Days 7 and 28 after vaccination. ]
- 1) Development of serum antibody assessed by either HAI or microneutralization (MN) assays.2) Development of 200 influenza-specific interferon-gamma (IFN- >=)-secreting cells per million lymphocytes as assessed by enzymelinked immunospo... [ Time Frame: One week prior to and 2 days after vaccine administration, and on Days 7 and 28 after vaccination. ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01730144
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Tara N Palmore, M.D.||National Institute of Allergy and Infectious Diseases (NIAID)|