Normal PhysiologyNCT01730144
Studying Cell Immune Responses to a Live Flu Vaccine in Healthy Adults
An observational study of Normal Physiology, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial summary
Background: 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. Read more about this study
- Who is it for?
- Ages 18 to 49 yearsHealthy volunteers can take part
- Conditions the study is for
- Normal Physiology
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- 17 Nov 2012to 12 Jul 2019
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 49 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Adult males and females between 18 and 49 years of age.
- Females of child-bearing potential must have a negative serum beta-human choriogonadotropin (HCG) on Day -7 and agree to use an effective birth control method 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, surgical sterilization). All female subjects 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.
- General good health, without significant medical illness, physical examination findings, or significant laboratory abnormalities as determined by the investigator.
- Agree to storage of blood, NP swab, and RNA specimens for future research.
- Available for the duration of the study. Subjects must be willing and able to make follow-up visits as specified by the protocol.
Who cannot join
- Any contraindiciations for adults for the receipt of LAIV:
- --Hypersensitivity to eggs, egg proteins, gentamicin, gelatin, or arginine,or life-threatening reactions to previous influenza vaccination.
- Currently breast-feeding.
- Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, rheumatologic, autoimmune, or renal disease by history, physical examination, and/or laboratory studies including urine testing. Clinically significant alanine aminotransferase (ALT) levels, as determined by one of the protocol investigators will be exclusionary at baseline, prior to vaccination.
- Evidence of upper respiratory tract illness (URI) including fever, sore throat, and rhinorrhea. Enrollment of subjects with evidence of URI on Study Day -7 will be temporarily deferred.
- Deviated nasal septum or nasal obstruction.
Show all 29Show fewer
- Body Mass Index greater than 35.
- NIH employee involved in direct patient care, consistent with the NIH CC policy that employees should avoid patient care for 5 days following receipt of LAIV. In addition, NIH employees must not be under the supervision of the study principal or associate investigators.
- 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.
- Seropositive to the influenza A component viruses of seasonal LAIV (serum HAI titer of greater than or equal to 1:10).
- Has had 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 subject participating in the study or would render the subject unable to comply with the protocol.
- History of anaphylaxis.
- Current diagnosis of asthma or reactive airway disease (within the past 2 years).
- History of Guillain-Barr(SqrRoot)(Copyright) Syndrome.
- Positive enzyme-linked immunosorbent assay (ELISA) and confirmatory Western blot tests for human immunodeficiency virus-1 (HIV-1).
- Positive ELISA and confirmatory test (e.g., recombinant immunoblotassay) for hepatitis C virus (HCV).
- Positive hepatitis B virus surface antigen (HBsAg) by ELISA.
- Known immunodeficiency syndrome.
- Use of oral, injected, or inhaled corticosteroids (excluding topical preparations) or immunosuppressive drugs within 30 days prior to enrollment in the study.
- Use of any herbal supplement 30 days prior to study enrollment.
- Receipt of 2012-2013 influenza vaccine (TIV or LAIV).
- Receipt of a live vaccine within 4 weeks or a killed vaccine within 2 weeks prior to enrollment in the study.
- History of a surgical splenectomy.
- Receipt of blood or blood-derived products (including immunoglobulin) within 6 months prior to study vaccination.
- Current smoker.
- Travel to the Southern Hemisphere 30 days prior to study enrollment or anticipated travel to the Southern Hemisphere during the study.
- Travel on a cruise ship 30 days prior to study enrollment or anticipated travel on a cruise ship during the study.
- Receipt of another investigational vaccine or drug within 30 days prior to enrollment in the study.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Elucidation of the Mucosal Immune Responses to Live Attenuated Influenza Vaccine In Healthy Adults
Background:
- 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.
Read more
Objectives:
- To look at immune changes in nasal and blood cells in people who receive live flu vaccine.
Eligibility:
- Healthy volunteers between 18 and 49 years of age.
Design:
- 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.
Read the detailed description
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.
- Conditions
- Normal Physiology
- Keywords
- Nasal Spray Vaccine, Nasal Cells
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: One week prior to and 2 days after vaccine administration and on Days 7 and 28 after vaccination.
Secondary outcomes (1)
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...
Measured: One week prior to and 2 days after vaccine administration, and on Days 7 and 28 after vaccination.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Nov 2012 (estimated)
- Study start17 Nov 2012
- Primary completion17 Apr 2013
- Study completion12 Jul 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Normal PhysiologyStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Other
- Time perspective
- Prospective
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Tara N Palmore, M.D., Principal investigator, National Institute of Allergy and Infectious Diseases (NIAID)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01730144
- Sponsor's protocol ID
- 130020
- Other IDs
- 13-I-0020
- Status last verified
- 12 Jul 2019
- First submitted
- 17 Nov 2012
- Last updated
- 18 Oct 2019
- Results posted
- No
Publications
Sen A, Rothenberg ME, Mukherjee G, Feng N, Kalisky T, Nair N, Johnstone IM, Clarke MF, Greenberg HB. Innate immune response to homologous rotavirus infection in the small intestinal villous epithelium at single-cell resolution. Proc Natl Acad Sci U S A. 2012 Dec 11;109(50):20667-72. doi: 10.1073/pnas.1212188109. Epub 2012 Nov 27.
PubMed 23188796Nakaya HI, Wrammert J, Lee EK, Racioppi L, Marie-Kunze S, Haining WN, Means AR, Kasturi SP, Khan N, Li GM, McCausland M, Kanchan V, Kokko KE, Li S, Elbein R, Mehta AK, Aderem A, Subbarao K, Ahmed R, Pulendran B. Systems biology of vaccination for seasonal influenza in humans. Nat Immunol. 2011 Jul 10;12(8):786-95. doi: 10.1038/ni.2067.
PubMed 21743478Zhu W, Higgs BW, Morehouse C, Streicher K, Ambrose CS, Woo J, Kemble GW, Jallal B, Yao Y. A whole genome transcriptional analysis of the early immune response induced by live attenuated and inactivated influenza vaccines in young children. Vaccine. 2010 Apr 1;28(16):2865-76. doi: 10.1016/j.vaccine.2010.01.060. Epub 2010 Feb 12.
PubMed 20153794
Study at a glance
From the registry record, last updated by the sponsor on 18 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Elucidation of the Mucosal Immune Responses to Live Attenuated Influenza Vaccine In Healthy Adults
- ClinicalTrials.gov ID
- NCT01730144
- Acronym / sponsor ID
- 130020
- Conditions
- Normal Physiology
- Keywords
- Nasal Spray Vaccine, Nasal Cells
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 17 Nov 2012
- Primary completion
- 17 Apr 2013 (actual)
- Study completion
- 12 Jul 2019 (actual)
- First posted
- 21 Nov 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
- 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.
Objectives:
- To look at immune changes in nasal and blood cells in people who receive live flu vaccine.
Eligibility:
- Healthy volunteers between 18 and 49 years of age.
Design:
- 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.
Detailed description
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 design
- Observational model
- Other
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 to 49 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Adult males and females between 18 and 49 years of age.
- Females of child-bearing potential must have a negative serum beta-human choriogonadotropin (HCG) on Day -7 and agree to use an effective birth control method 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, surgical sterilization). All female subjects 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.
- General good health, without significant medical illness, physical examination findings, or significant laboratory abnormalities as determined by the investigator.
- Agree to storage of blood, NP swab, and RNA specimens for future research.
- Available for the duration of the study. Subjects must be willing and able to make follow-up visits as specified by the protocol.
Key exclusion criteria (29 listed)
- Any contraindiciations for adults for the receipt of LAIV:
- --Hypersensitivity to eggs, egg proteins, gentamicin, gelatin, or arginine,or life-threatening reactions to previous influenza vaccination.
- Currently breast-feeding.
- Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, rheumatologic, autoimmune, or renal disease by history, physical examination, and/or laboratory studies including urine testing. Clinically significant alanine aminotransferase (ALT) levels, as determined by one of the protocol investigators will be exclusionary at baseline, prior to vaccination.
- Evidence of upper respiratory tract illness (URI) including fever, sore throat, and rhinorrhea. Enrollment of subjects with evidence of URI on Study Day -7 will be temporarily deferred.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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 secondary outcome
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Oct 2019.
- Background: PubMed 23188796Sen A, Rothenberg ME, Mukherjee G, Feng N, Kalisky T, Nair N, Johnstone IM, Clarke MF, Greenberg HB. Innate immune response to homologous rotavirus infection in the small intestinal villous epithelium at single-cell resolution. Proc Natl Acad Sci U S A. 2012 Dec 11;109(50):20667-72. doi: 10.1073/pnas.1212188109. Epub 2012 Nov 27.
- Background: PubMed 21743478Nakaya HI, Wrammert J, Lee EK, Racioppi L, Marie-Kunze S, Haining WN, Means AR, Kasturi SP, Khan N, Li GM, McCausland M, Kanchan V, Kokko KE, Li S, Elbein R, Mehta AK, Aderem A, Subbarao K, Ahmed R, Pulendran B. Systems biology of vaccination for seasonal influenza in humans. Nat Immunol. 2011 Jul 10;12(8):786-95. doi: 10.1038/ni.2067.
- Background: PubMed 20153794Zhu W, Higgs BW, Morehouse C, Streicher K, Ambrose CS, Woo J, Kemble GW, Jallal B, Yao Y. A whole genome transcriptional analysis of the early immune response induced by live attenuated and inactivated influenza vaccines in young children. Vaccine. 2010 Apr 1;28(16):2865-76. doi: 10.1016/j.vaccine.2010.01.060. Epub 2010 Feb 12.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Tara N Palmore, M.D. principal investigator
National Institute of Allergy and Infectious Diseases (NIAID)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Normal Physiology, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01730144, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Oct 2019.