InfluenzaPhase 4NCT02385123
Evaluation of Human Immune Responses to Influenza Virus Vaccination in Healthy Volunteers
A Phase 4 study testing Influenza Virus Vaccine Inactivated in people with Influenza and Influenza Immunisation, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial summary
This was an open label, single arm, Phase IV study of longitudinal immunologic responses to influenza vaccine in healthy adult participants, with the aim of enrolling up to 70 participants. This study enrolled males and non-pregnant females, 18-49 years old, inclusive. Read more about this study
- Who is it for?
- Ages 18 to 49 yearsHealthy volunteers can take part
- Conditions the study is for
- Influenza, Influenza Immunisation
- What is being tested?
- Influenza Virus Vaccine Inactivated
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Apr 2015to 31 Dec 2020
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Male or female subjects between 18 and 49 years of age, inclusive.
- Subjects capable of providing written informed consent prior to initiation of any study procedures. Subjects able to understand and comply with planned study procedures and be available for all study visits.
- Screening labs within normal limits per the local laboratory normal ranges or considered to be not clinically significant by the investigator. Normal laboratory ranges are as listed below:
- Hematology:
- Hemoglobin: Male- 12.9-16.1 gm/dL, Female- 11.4-14.4 gm/dL
- White blood cells (WBC): Male- 4.2-9.2 upper limit (uL), Female- 4-10 upper limit (uL)
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- Platelet count: 150-400 upper limit (uL)
- Chemistries:
- Kidney function: Glomerular filtration rate (GFR) > / = 60 mL/min/1.73 m^2;
- Liver enzymes: Albumin > / = 3.5 g/dL; alanine aminotransferase (ALT) <66 U/L; aspartate aminotransferase (AST) <62 U/L
- Subjects who have not received the seasonal influenza vaccine in the current flu season and are not suspected to have had an influenza infection in the current flu season.
- Female subjects of child bearing potential must have a negative urine pregnancy test at the screening visit, enrollment visit and all subsequent study visits longer than 14 days since the last pregnancy test.
Who cannot join
- Known infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B virus (HBV). This information will be obtained verbally from the patient.
- If female, active pregnancy or breast-feeding or plans to become pregnant during study participation.
- Chronic medical conditions that cause immunodeficiency or that require medications which could alter immune function such as immunosuppressants and immunoenhancers.
- Have any medical disease or condition that, in the opinion of the site principal investigator or appropriate sub-investigator, is a contraindication to study participation. This includes any chronic medical disease or condition, defined as persisting 3 months (defined as 90 days) or longer, that would place the subject at an unacceptable risk of injury, render the subject unable to meet the requirements of the protocol, or may interfere with the evaluation of responses or the subject's successful completion of this study
- Have an acute illness, as determined by the site principal investigator or appropriate sub-investigator, within 72 hours prior to study vaccination. An acute illness which is nearly resolved with only minor residual symptoms remaining is allowable if, in the opinion of the site principal investigator or appropriate sub-investigator, the residual symptoms will not interfere with the ability to assess safety parameters as required by the protocol.
- Persons taking anticoagulants, long-term aspirin therapy, or long-term systemic steroids (greater than 3 months in the past 12 months and any within 30 days).
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- Have known hypersensitivity or allergy to eggs, egg or chicken protein, or other components of the study vaccine;
- Have a known latex allergy;
- Have a history of severe reactions following previous immunization with licensed influenza virus vaccines.
- Have a history of Guillain-Barre syndrome.
- Subjects who had or are suspected to have had an influenza infection in the current influenza season.
- Subjects who, at screening, have abnormal vital signs and/or physical exam, including a temperature > / = 38.0 C, Systolic blood pressure < / = 90 or > / = 160 mmHg, pulse < / = 60 or > 110 beats per minute, new rash, signs of infection.
- Subjects who have already received the seasonal influenza vaccine in the current influenza vaccination season.
Trial locations and contacts
1 site in 1 country.
United States1 site
Emory University Hospital - W. Dean Warren General Clinical Research Center (GCRC)
Atlanta, Georgia, 30322-1059
About this study
This was an open label, single arm, Phase IV study of longitudinal immunologic responses to influenza vaccine in healthy adult participants, with the aim of enrolling up to 70 participants. This study enrolled males and non-pregnant females, 18-49 years old, inclusive. The participants were screened at enrollment with a history and physical exam and laboratory testing to ensure they were healthy enough to participate. Total enrollment was 60 participants.
Qualifying participants were vaccinated with an FDA approved seasonal inactivated influenza vaccine (IIV) according to the package insert. The study enrolled a total 60 participants. The primary objective of the study was to characterize HA-specific plasmablasts and memory B cells after influenza vaccination.
Note: Due to the Coronavirus Disease 2019 (COVID-19) pandemic, all non-essential research was halted in mid-March 2020. New enrollments were placed on hold for this study. Follow-up visits were also halted, which impacted the timing of participants' subsequent follow-up visits. Five participants had their Day 180 visits halted due to the COVID-19 pandemic.
Read the detailed description
This was an open label, single arm, Phase IV study of longitudinal immunologic responses to influenza vaccine in healthy adult participants. This study enrolled males and non-pregnant females, 18-49 years old. The primary objective of the study was to characterize hemagglutinin (HA)-specific plasmablasts and memory B cells after influenza vaccination. The secondary objective was to investigate the longevity of humoral immunity to influenza virus in humans. Total enrollment was 60 participants.
This was a multi-year study. Participant duration in this study was 180 days. Participants were screened at enrollment with a history and physical exam and laboratory testing to ensure they were healthy enough to participate. Qualifying participants were vaccinated with an FDA approved seasonal inactivated influenza vaccine (IIV) according to the package insert. Approximately 450 ml of blood was collected for the research assays during the course of the study. Specifically, 16 ml was be collected for screening; 48ml was collected at enrollment; 96ml was collected at visit Days 7 and 14; and 64 ml was collected at 28, 90, and 180 days post vaccination.
A total of 60 participants were enrolled over the course of the study. Participants who completed the study were given the option to re-enroll in subsequent years as long as they continued to meet all inclusion/exclusion criteria. Re-enrolling participants were re-consented, given new participants identifiers, and counted towards the enrollment number goal for each year of participation. Safety was assessed from the time of study enrollment through the last study visit, via monitoring of vital signs, and querying for change in health status.
Note: Due to the Coronavirus Disease 2019 (COVID-19) pandemic, all non-essential research was halted in mid-March 2020. New enrollments were placed on hold for this study. Follow-up visits were also halted, which impacted the timing of participants' subsequent follow-up visits. Five participants had their Day 180 visits halted due to the COVID-19 pandemic.
A request was submitted to the Emory University Institutional Review Board to extend the missed visit windows for the Day 180 visit for a maximum of up to 90 days, to ensure that ample time would be available to bring participants back for their missed visits. Enrollment for this study ended on September 30, 2020, before research activities could resume at Emory.
- Conditions
- Influenza, Influenza Immunisation
- Being tested
- Influenza Virus Vaccine Inactivated
- Keywords
- ex-vivo, Healthy Volunteers, Immune Response, Influenza, plasmablasts, Vaccine
- Medical subject headings
- Influenza, Human
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Influenza Virus Vaccine InactivatedBiological
A synthetic vaccine consisting of three inactivated influenza viruses: two different influenza type A strains and one influenza type B strain. Trivalent influenza vaccine is formulated annually, based on influenza strains projected to be prevalent in the upcoming flu season.
| Study group | Role | What they receive |
|---|---|---|
| Seasonal Flu Vaccine/Healthy Adult Volunteers | Experimental | 0.5 ml of seasonal inactivated influenza vaccine (IIV) was administered intramuscularly (IM) on Day 0 of each study season, for this multi-year study. A total of 60 participants were enrolled in this study. Receives: Biological: Influenza Virus Vaccine Inactivated |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Subjects Achieving Seroconversion (Pre-vaccination Hemagglutination Inhibition (HI) Titer <1:10 and a Post-vaccination HI Titer >1:40 or a Pre-vaccination HI Titer >1:10 and a Minimum Four-fold Rise in Post-vaccination HI Antibody Titer)
Hemagglutination inhibition titers were measured against reference influenza A/H1N1 and A/H3N2 strains, as well as influenza B Yamagata lineage influenza strains. Strains were matched to the composition of the vaccine received by each subject. For H1N1 and H3N2, hemagglutination was performed using receptor destroying enzyme (RDE)-treated plasma and turkey red blood cells following the World Health Organization (WHO) standard protocol. For influenza B, guinea pig red blood cells were used instead.
Measured: Day 28
Percentage of Subjects With Pre-vaccination Titer <1:40
Hemagglutination inhibition titers were measured against reference influenza A/H1N1 and A/H3N2 strains, as well as influenza B Yamagata lineage influenza strains. Strains were matched to the composition of the vaccine received by each subject. For H1N1 and H3N2, hemagglutination was performed using RDE-treated plasma and turkey red blood cells following the WHO standard protocol. For influenza B, guinea pig red blood cells were used instead.
Measured: Day 0
Secondary outcomes (21)
Endpoint Immunoglobulin G (IgG) Titers for Serum Antibody Responses Directed Against the Full Length A/H1N1 Hemagglutinin (HA) Protein
ELISAs were performed using serial dilutions of plasma incubated on Maxisorp ELISA plates coated with 50 nanograms per well of H1N1 hemagglutinin protein from strain A/Michigan/45/2015. Plasma samples were drawn from donors who received the 2017-18 or 2018-19 influenza vaccine. Bound serum IgG was detected using 1:1000 diluted goat anti-human IgG-horseradish peroxidase (HRP) from Jackson Immunoresearch and plates were developed using o-phenylenediamine (OPD) substrate and developed for 7 minutes. The ELISA endpoint titer was defined as the reciprocal dilution of plasma that produced a background-subtracted optical density at 490 (OD490) value of 0.3, corresponding to 10% of maximum binding. Endpoint titers were determined by interpolation from the serial dilution curve results using Graphpad Prism software.
Measured: Day 0
Endpoint IgG Titers for Serum Antibody Responses Directed Against the Full Length A/H1N1 Hemagglutinin (HA) Protein
ELISAs were performed using serial dilutions of plasma incubated on Maxisorp ELISA plates coated with 50 nanograms per well of H1N1 hemagglutinin protein from strain A/Michigan/45/2015. Plasma samples were drawn from donors who received the 2017-18 or 2018-19 influenza vaccine. Bound serum IgG was detected using 1:1000 diluted goat anti-human IgG-HRP from Jackson Immunoresearch and plates were developed using OPD substrate and developed for 7 minutes. The ELISA endpoint titer was defined as the reciprocal dilution of plasma that produced a background-subtracted OD490 value of 0.3, corresponding to 10% of maximum binding. Endpoint titers were determined by interpolation from the serial dilution curve results using Graphpad Prism software.
Measured: Day 180
Endpoint IgG Titers for Serum Antibody Responses Directed Against the Full Length A/H1N1 Hemagglutinin (HA) Protein
ELISAs were performed using serial dilutions of plasma incubated on Maxisorp ELISA plates coated with 50 nanograms per well of H1N1 hemagglutinin protein from strain A/Michigan/45/2015. Plasma samples were drawn from donors who received the 2017-18 or 2018-19 influenza vaccine. Bound serum IgG was detected using 1:1000 diluted goat anti-human IgG-HRP from Jackson Immunoresearch and plates were developed using OPD substrate and developed for 7 minutes. The ELISA endpoint titer was defined as the reciprocal dilution of plasma that produced a background-subtracted OD490 value of 0.3, corresponding to 10% of maximum binding. Endpoint titers were determined by interpolation from the serial dilution curve results using Graphpad Prism software.
Measured: Day 28
Endpoint IgG Titers for Serum Antibody Responses Directed Against the H1N1 Hemagglutinin (HA) Stem Region
ELISAs were performed using serial dilutions of plasma incubated on Maxisorp ELISA plates coated with 50 nanograms per well of a chimeric HA protein containing the head domain from an H6 influenza virus and the stem domain from A/California/07/2009. Plasma samples were drawn from donors who received the 2017-18 or 2018-19 influenza vaccine. Bound serum IgG was detected using 1:1000 diluted goat anti-human IgG-HRP from Jackson Immunoresearch and plates were developed using OPD substrate and developed for 7 minutes. The ELISA endpoint titer was defined as the reciprocal dilution of plasma that produced a background-subtracted OD490 value of 0.3, corresponding to 10% of maximum binding. Endpoint titers were determined by interpolation from the serial dilution curve results using Graphpad Prism software.
Measured: Day 0
Endpoint IgG Titers for Serum Antibody Responses Directed Against the H1N1 Hemagglutinin (HA) Stem Region
ELISAs were performed using serial dilutions of plasma incubated on Maxisorp ELISA plates coated with 50 nanograms per well of a chimeric HA protein containing the head domain from an H6 influenza virus and the stem domain from A/California/07/2009. Plasma samples were drawn from donors who received the 2017-18 or 2018-19 influenza vaccine. Bound serum IgG was detected using 1:1000 diluted goat anti-human IgG-HRP from Jackson Immunoresearch and plates were developed using OPD substrate and developed for 7 minutes. The ELISA endpoint titer was defined as the reciprocal dilution of plasma that produced a background-subtracted OD490 value of 0.3, corresponding to 10% of maximum binding. Endpoint titers were determined by interpolation from the serial dilution curve results using Graphpad Prism software.
Measured: Day 180
Endpoint IgG Titers for Serum Antibody Responses Directed Against the H1N1 Hemagglutinin (HA) Stem Region.
ELISAs were performed using serial dilutions of plasma incubated on Maxisorp ELISA plates coated with 50 nanograms per well of a chimeric HA protein containing the head domain from an H6 influenza virus and the stem domain from A/California/07/2009. Plasma samples were drawn from donors who received the 2017-18 or 2018-19 influenza vaccine. Bound serum IgG was detected using 1:1000 diluted goat anti-human IgG-HRP from Jackson Immunoresearch and plates were developed using OPD substrate and developed for 7 minutes. The ELISA endpoint titer was defined as the reciprocal dilution of plasma that produced a background-subtracted OD490 value of 0.3, corresponding to 10% of maximum binding. Endpoint titers were determined by interpolation from the serial dilution curve results using Graphpad Prism software.
Measured: Day 28
Expression of Human Influenza-specific Monoclonal Antibodies From Plasmablasts
Monoclonal antibodies were cloned from sorted H1 hemagglutinin-binding cells expressing high levels of the CD38 protein (CD38hi) plasmablasts isolated from a single donor on day 7 post vaccination.
Measured: Day 7
Frequency of Hemagglutinin (HA) Head-specific IgG Secreting Memory B Cells Per Total IgG Secreting Cells
Peripheral blood mononuclear cells from volunteers who received the 2017-18 or 2018-19 influenza vaccine were stimulated with R-848/interleukin (IL)-2 to induce polyclonal plasmablast differentiation. Total H1-specific memory B cells were detected using hemagglutinin protein from A/Michigan/45/2015 as an ELISPOT capture antigen and IgG detection. Frequencies were expressed as a percentage of the spots observed using total IgG capture antibody. Head specific memory B cell frequencies were calculated by subtracting the percentage of stem-specific IgG memory B cells from the percentage of total H1-specific cells.
Measured: Day 0
Frequency of Hemagglutinin (HA) Head-specific IgG Secreting Memory B Cells Per Total IgG Secreting Cells
Peripheral blood mononuclear cells from volunteers who received the 2017-18 or 2018-19 influenza vaccine were stimulated with R-848/IL-2 to induce polyclonal plasmablast differentiation. Total H1-specific memory B cells were detected using hemagglutinin protein from A/Michigan/45/2015 as an ELISPOT capture antigen and IgG detection. Frequencies were expressed as a percentage of the spots observed using total IgG capture antibody. Head specific memory B cell frequencies were calculated by subtracting the percentage of stem-specific IgG memory B cells from the percentage of total H1-specific cells.
Measured: Day 180
Frequency of Hemagglutinin (HA) Head-specific IgG Secreting Memory B Cells Per Total IgG Secreting Cells
Peripheral blood mononuclear cells from volunteers who received the 2017-18 or 2018-19 influenza vaccine were stimulated with R-848/IL-2 to induce polyclonal plasmablast differentiation. Total H1-specific memory B cells were detected using hemagglutinin protein from A/Michigan/45/2015 as an ELISPOT capture antigen and IgG detection. Frequencies were expressed as a percentage of the spots observed using total IgG capture antibody. Head specific memory B cell frequencies were calculated by subtracting the percentage of stem-specific IgG memory B cells from the percentage of total H1-specific cells.
Measured: Day 28
Frequency of Hemagglutinin (HA) Stem-specific IgG Secreting Memory B Cells Per Total IgG Secreting Cells
Peripheral blood mononuclear cells from volunteers who received the 2017-18 or 2018-19 influenza vaccine were stimulated with R-848/IL-2 to induce polyclonal plasmablast differentiation. Stem-specific memory B cells were detected using a chimeric hemagglutinin containing an H6 influenza head domain and the stem domain from A/California/07/2009 as an ELISPOT capture antigen. Frequencies were expressed as a percentage of the spots observed using total IgG capture antibody.
Measured: Day 0
Frequency of Hemagglutinin (HA) Stem-specific IgG Secreting Memory B Cells Per Total IgG Secreting Cells
Peripheral blood mononuclear cells from volunteers who received the 2017-18 or 2018-19 influenza vaccine were stimulated with R-848/IL-2 to induce polyclonal plasmablast differentiation. Stem-specific memory B cells were detected using a chimeric hemagglutinin containing an H6 influenza head domain and the stem domain from A/California/07/2009 as an ELISPOT capture antigen. Frequencies were expressed as a percentage of the spots observed using total IgG capture antibody.
Measured: Day 180
Frequency of Hemagglutinin (HA) Stem-specific IgG Secreting Memory B Cells Per Total IgG Secreting Cells
Peripheral blood mononuclear cells from volunteers who received the 2017-18 or 2018-19 influenza vaccine were stimulated with R-848/IL-2 to induce polyclonal plasmablast differentiation. Stem-specific memory B cells were detected using a chimeric hemagglutinin containing an H6 influenza head domain and the stem domain from A/California/07/2009 as an ELISPOT capture antigen. Frequencies were expressed as a percentage of the spots observed using total IgG capture antibody.
Measured: Day 28
Function of Human Influenza-specific Monoclonal Antibodies Assessed by Virus Neutralization Assay
Madin-Darby canine kidney (MDCK) cells in 96-well plates were infected in duplicate for 5 hours with H1N1 influenza virus (strain A/Michigan/45/2015) that had been pre-incubated for 15 minutes at 37 degrees with influenza monoclonal antibodies. Pre-incubations were performed using serial 2-fold dilutions of each monoclonal antibody, beginning at a concentration of 30 micrograms per milliliter. Virus was used at a dose sufficient to yield 5% infection in the absence of antibody. Infection was assessed after 5 hours in methanol-permeabilized cells by staining with an influenza nucleoprotein-specific mouse antibody (HB65), then phycoerythrin (PE)-conjugated anti-mouse IgG, followed by identification of PE-positive cells by flow cytometry. The 50% neutralizing titer reported is equivalent to the lowest monoclonal antibody concentration that resulted in a greater than or equal to 2-fold reduction in viral infection relative to the no-antibody control.
Measured: Day 7
Function of Human Influenza-specific Monoclonal Antibodies Assessed by Enzyme-Linked Immunosorbent Assay (ELISA)
Influenza-specific mAbs were assessed for HA binding by ELISA using recombinant HA protein from H1N1 strain A/California/07/2009. 50 ng of HA were coated per well in Maxisorp ELISA plates and serial dilutions of mAb were added. The concentration of each mAb that gave 50% maximal binding (EC50) was determined.
Measured: Day 7
Function of Human Influenza-specific Monoclonal Antibodies Assessed by Hemagglutination Inhibition (HAI) Assay
The HAI titer for each antibody was determined using the World Health Organization (WHO) standard protocol using H1N1 strain A/Michigan/45/2015.
Measured: Day 7
Quadrivalent Influenza Vaccine Immunoglobulin Gamma-1 (IgG1) ELISA Endpoint Titer
ELISA titers were measured against the matched seasonal quadrivalent inactivated influenza vaccine received by each subject using a secondary antibody specific for human IgG1. The endpoint ELISA titer was defined as the reciprocal dilution of plasma that gave an optical density (OD) reading of 0.2, which corresponded to ~3 standard deviations above the background OD for ELISA wells incubated without plasma.
Measured: Day 0
Quadrivalent Influenza Vaccine IgG1 ELISA Endpoint Titer
ELISA titers were measured against the matched seasonal quadrivalent inactivated influenza vaccine received by each subject using a secondary antibody specific for human IgG1. The endpoint ELISA titer was defined as the reciprocal dilution of plasma that gave an optical density (OD) reading of 0.2, which corresponded to ~3 standard deviations above the background OD for ELISA wells incubated without plasma.
Measured: Day 180
Quadrivalent Influenza Vaccine IgG1 ELISA Endpoint Titer
ELISA titers were measured against the matched seasonal quadrivalent inactivated influenza vaccine received by each subject using a secondary antibody specific for human IgG1. The endpoint ELISA titer was defined as the reciprocal dilution of plasma that gave an optical density (OD) reading of 0.2, which corresponded to ~3 standard deviations above the background OD for ELISA wells incubated without plasma.
Measured: Day 28
Plasmablast Responses Against Hemagglutinin (HA) Head Antigens Assessed by Direct ex Vivo Enzyme-linked Immunospot (ELISPOT)
Plasmablasts (PB) were enumerated directly from frozen PBMC without stimulation. Total H1-specific cells were detected using hemagglutinin protein from A/Michigan/45/2015 as an ELISPOT capture antigen and IgG detection. Frequencies were expressed as the number of spots observed per million peripheral blood mononuclear cells. Head specific PB frequencies were calculated by subtracting the number of stem-specific PB per million peripheral blood mononuclear cells from the number of total H1-specific PB per million cells.
Measured: Day 7
Plasmablast Responses Against Hemagglutinin (HA) Stem Antigens Assessed by Direct ex Vivo Enzyme-linked Immunospot (ELISPOT)
Plasmablasts (PB) were enumerated directly from frozen PBMC without stimulation. Stem-specific cells were detected using a chimeric hemagglutinin containing an H6 influenza head domain and the stem domain from A/California/07/2009 as an ELISPOT capture antigen and IgG detection. Frequencies were expressed as the number of spots observed per million peripheral blood mononuclear cells.
Measured: Day 7
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Mar 2015 (estimated)
- Study start1 Apr 2015
- Primary completion6 Dec 2019
- Study completion31 Dec 2020
Why it stopped: Study was terminated due to COVID-19 pandemic.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for InfluenzaStudies 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
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Aneesh Mehta, MD, Principal investigator, Emory University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02385123
- Sponsor's protocol ID
- 14-0071
- Other IDs
- HHSN272201400004C
- Status last verified
- Nov 2018
- First submitted
- 5 Mar 2015
- Last updated
- 25 Oct 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Thompson WW, Shay DK, Weintraub E, Brammer L, Cox N, Anderson LJ, Fukuda K. Mortality associated with influenza and respiratory syncytial virus in the United States. JAMA. 2003 Jan 8;289(2):179-86. doi: 10.1001/jama.289.2.179.
PubMed 12517228Centers for Disease Control and Prevention (CDC). Prevention and control of seasonal influenza with vaccines. Recommendations of the Advisory Committee on Immunization Practices--United States, 2013-2014. MMWR Recomm Rep. 2013 Sep 20;62(RR-07):1-43.
PubMed 24048214Kunzel W, Glathe H, Engelmann H, Van Hoecke C. Kinetics of humoral antibody response to trivalent inactivated split influenza vaccine in subjects previously vaccinated or vaccinated for the first time. Vaccine. 1996 Aug;14(12):1108-10. doi: 10.1016/0264-410x(96)00061-8.
PubMed 8911005Pica N, Palese P. Toward a universal influenza virus vaccine: prospects and challenges. Annu Rev Med. 2013;64:189-202. doi: 10.1146/annurev-med-120611-145115.
PubMed 23327522
Study at a glance
From the registry record, last updated by the sponsor on 25 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Human Immune Responses to Influenza Virus Vaccination in Healthy Volunteers
- ClinicalTrials.gov ID
- NCT02385123
- Acronym / sponsor ID
- 14-0071
- Conditions
- Influenza, Influenza Immunisation
- Keywords
- ex-vivo, Healthy Volunteers, Immune Response, Influenza, plasmablasts, Vaccine
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study was terminated due to COVID-19 pandemic.
- Enrolment
- 60 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 1 Apr 2015 (actual)
- Primary completion
- 6 Dec 2019 (actual)
- Study completion
- 31 Dec 2020 (actual)
- First posted
- 11 Mar 2015 (estimated)
- Results
- Posted 25 Oct 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This was an open label, single arm, Phase IV study of longitudinal immunologic responses to influenza vaccine in healthy adult participants, with the aim of enrolling up to 70 participants. This study enrolled males and non-pregnant females, 18-49 years old, inclusive. The participants were screened at enrollment with a history and physical exam and laboratory testing to ensure they were healthy enough to participate. Total enrollment was 60 participants.
Qualifying participants were vaccinated with an FDA approved seasonal inactivated influenza vaccine (IIV) according to the package insert. The study enrolled a total 60 participants. The primary objective of the study was to characterize HA-specific plasmablasts and memory B cells after influenza vaccination.
Note: Due to the Coronavirus Disease 2019 (COVID-19) pandemic, all non-essential research was halted in mid-March 2020. New enrollments were placed on hold for this study. Follow-up visits were also halted, which impacted the timing of participants' subsequent follow-up visits. Five participants had their Day 180 visits halted due to the COVID-19 pandemic.
Detailed description
This was an open label, single arm, Phase IV study of longitudinal immunologic responses to influenza vaccine in healthy adult participants. This study enrolled males and non-pregnant females, 18-49 years old. The primary objective of the study was to characterize hemagglutinin (HA)-specific plasmablasts and memory B cells after influenza vaccination. The secondary objective was to investigate the longevity of humoral immunity to influenza virus in humans. Total enrollment was 60 participants.
This was a multi-year study. Participant duration in this study was 180 days. Participants were screened at enrollment with a history and physical exam and laboratory testing to ensure they were healthy enough to participate. Qualifying participants were vaccinated with an FDA approved seasonal inactivated influenza vaccine (IIV) according to the package insert. Approximately 450 ml of blood was collected for the research assays during the course of the study. Specifically, 16 ml was be collected for screening; 48ml was collected at enrollment; 96ml was collected at visit Days 7 and 14; and 64 ml was collected at 28, 90, and 180 days post vaccination.
A total of 60 participants were enrolled over the course of the study. Participants who completed the study were given the option to re-enroll in subsequent years as long as they continued to meet all inclusion/exclusion criteria. Re-enrolling participants were re-consented, given new participants identifiers, and counted towards the enrollment number goal for each year of participation. Safety was assessed from the time of study enrollment through the last study visit, via monitoring of vital signs, and querying for change in health status.
Note: Due to the Coronavirus Disease 2019 (COVID-19) pandemic, all non-essential research was halted in mid-March 2020. New enrollments were placed on hold for this study. Follow-up visits were also halted, which impacted the timing of participants' subsequent follow-up visits. Five participants had their Day 180 visits halted due to the COVID-19 pandemic.
A request was submitted to the Emory University Institutional Review Board to extend the missed visit windows for the Day 180 visit for a maximum of up to 90 days, to ensure that ample time would be available to bring participants back for their missed visits. Enrollment for this study ended on September 30, 2020, before research activities could resume at Emory.
Study design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Seasonal Flu Vaccine/Healthy Adult Volunteers | Experimental | Biological: Influenza Virus Vaccine Inactivated0.5 ml of seasonal inactivated influenza vaccine (IIV) was administered intramuscularly (IM) on Day 0 of each study season, for this multi-year study. A total of 60 participants were enrolled in this study. |
Who may qualify
- Ages
- 18 to 49 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (12 listed)
- Male or female subjects between 18 and 49 years of age, inclusive.
- Subjects capable of providing written informed consent prior to initiation of any study procedures. Subjects able to understand and comply with planned study procedures and be available for all study visits.
- Screening labs within normal limits per the local laboratory normal ranges or considered to be not clinically significant by the investigator. Normal laboratory ranges are as listed below:
- Subjects who have not received the seasonal influenza vaccine in the current flu season and are not suspected to have had an influenza infection in the current flu season.
- Female subjects of child bearing potential must have a negative urine pregnancy test at the screening visit, enrollment visit and all subsequent study visits longer than 14 days since the last pregnancy test.
Key exclusion criteria (13 listed)
- Known infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B virus (HBV). This information will be obtained verbally from the patient.
- If female, active pregnancy or breast-feeding or plans to become pregnant during study participation.
- Chronic medical conditions that cause immunodeficiency or that require medications which could alter immune function such as immunosuppressants and immunoenhancers.
- Have any medical disease or condition that, in the opinion of the site principal investigator or appropriate sub-investigator, is a contraindication to study participation. This includes any chronic medical disease or condition, defined as persisting 3 months (defined as 90 days) or longer, that would place the subject at an unacceptable risk of injury, render the subject unable to meet the requirements of the protocol, or may interfere with the evaluation of responses or the subject's successful completion of this study
- Have an acute illness, as determined by the site principal investigator or appropriate sub-investigator, within 72 hours prior to study vaccination. An acute illness which is nearly resolved with only minor residual symptoms remaining is allowable if, in the opinion of the site principal investigator or appropriate sub-investigator, the residual symptoms will not interfere with the ability to assess safety parameters as required by the protocol.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Influenza Virus Vaccine InactivatedA synthetic vaccine consisting of three inactivated influenza viruses: two different influenza type A strains and one influenza type B strain. Trivalent influenza vaccine is formulated annually, based on influenza strains projected to be prevalent in the upcoming flu season. | Biological | Seasonal Flu Vaccine/Healthy Adult Volunteers |
Primary outcome
Percentage of Subjects Achieving Seroconversion (Pre-vaccination Hemagglutination Inhibition (HI) Titer <1:10 and a Post-vaccination HI Titer >1:40 or a Pre-vaccination HI Titer >1:10 and a Minimum Four-fold Rise in Post-vaccination HI Antibody Titer)
Time frame: Day 28
Hemagglutination inhibition titers were measured against reference influenza A/H1N1 and A/H3N2 strains, as well as influenza B Yamagata lineage influenza strains. Strains were matched to the composition of the vaccine received by each subject. For H1N1 and H3N2, hemagglutination was performed using receptor destroying enzyme (RDE)-treated plasma and turkey red blood cells following the World Health Organization (WHO) standard protocol. For influenza B, guinea pig red blood cells were used instead.
Percentage of Subjects With Pre-vaccination Titer <1:40
Time frame: Day 0
Hemagglutination inhibition titers were measured against reference influenza A/H1N1 and A/H3N2 strains, as well as influenza B Yamagata lineage influenza strains. Strains were matched to the composition of the vaccine received by each subject. For H1N1 and H3N2, hemagglutination was performed using RDE-treated plasma and turkey red blood cells following the WHO standard protocol. For influenza B, guinea pig red blood cells were used instead.
21 secondary outcomes
Endpoint Immunoglobulin G (IgG) Titers for Serum Antibody Responses Directed Against the Full Length A/H1N1 Hemagglutinin (HA) Protein
Time frame: Day 0
Endpoint IgG Titers for Serum Antibody Responses Directed Against the Full Length A/H1N1 Hemagglutinin (HA) Protein
Time frame: Day 180
Endpoint IgG Titers for Serum Antibody Responses Directed Against the Full Length A/H1N1 Hemagglutinin (HA) Protein
Time frame: Day 28
Endpoint IgG Titers for Serum Antibody Responses Directed Against the H1N1 Hemagglutinin (HA) Stem Region
Time frame: Day 0
Endpoint IgG Titers for Serum Antibody Responses Directed Against the H1N1 Hemagglutinin (HA) Stem Region
Time frame: Day 180
Endpoint IgG Titers for Serum Antibody Responses Directed Against the H1N1 Hemagglutinin (HA) Stem Region.
Time frame: Day 28
Expression of Human Influenza-specific Monoclonal Antibodies From Plasmablasts
Time frame: Day 7
Frequency of Hemagglutinin (HA) Head-specific IgG Secreting Memory B Cells Per Total IgG Secreting Cells
Time frame: Day 0
Frequency of Hemagglutinin (HA) Head-specific IgG Secreting Memory B Cells Per Total IgG Secreting Cells
Time frame: Day 180
Frequency of Hemagglutinin (HA) Head-specific IgG Secreting Memory B Cells Per Total IgG Secreting Cells
Time frame: Day 28
Frequency of Hemagglutinin (HA) Stem-specific IgG Secreting Memory B Cells Per Total IgG Secreting Cells
Time frame: Day 0
Frequency of Hemagglutinin (HA) Stem-specific IgG Secreting Memory B Cells Per Total IgG Secreting Cells
Time frame: Day 180
Frequency of Hemagglutinin (HA) Stem-specific IgG Secreting Memory B Cells Per Total IgG Secreting Cells
Time frame: Day 28
Function of Human Influenza-specific Monoclonal Antibodies Assessed by Virus Neutralization Assay
Time frame: Day 7
Function of Human Influenza-specific Monoclonal Antibodies Assessed by Enzyme-Linked Immunosorbent Assay (ELISA)
Time frame: Day 7
Function of Human Influenza-specific Monoclonal Antibodies Assessed by Hemagglutination Inhibition (HAI) Assay
Time frame: Day 7
Quadrivalent Influenza Vaccine Immunoglobulin Gamma-1 (IgG1) ELISA Endpoint Titer
Time frame: Day 0
Quadrivalent Influenza Vaccine IgG1 ELISA Endpoint Titer
Time frame: Day 180
Quadrivalent Influenza Vaccine IgG1 ELISA Endpoint Titer
Time frame: Day 28
Plasmablast Responses Against Hemagglutinin (HA) Head Antigens Assessed by Direct ex Vivo Enzyme-linked Immunospot (ELISPOT)
Time frame: Day 7
Plasmablast Responses Against Hemagglutinin (HA) Stem Antigens Assessed by Direct ex Vivo Enzyme-linked Immunospot (ELISPOT)
Time frame: Day 7
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Oct 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 12517228Thompson WW, Shay DK, Weintraub E, Brammer L, Cox N, Anderson LJ, Fukuda K. Mortality associated with influenza and respiratory syncytial virus in the United States. JAMA. 2003 Jan 8;289(2):179-86. doi: 10.1001/jama.289.2.179.
- Background: PubMed 24048214Centers for Disease Control and Prevention (CDC). Prevention and control of seasonal influenza with vaccines. Recommendations of the Advisory Committee on Immunization Practices--United States, 2013-2014. MMWR Recomm Rep. 2013 Sep 20;62(RR-07):1-43.
- Background: PubMed 8911005Kunzel W, Glathe H, Engelmann H, Van Hoecke C. Kinetics of humoral antibody response to trivalent inactivated split influenza vaccine in subjects previously vaccinated or vaccinated for the first time. Vaccine. 1996 Aug;14(12):1108-10. doi: 10.1016/0264-410x(96)00061-8.
- Background: PubMed 23327522Pica N, Palese P. Toward a universal influenza virus vaccine: prospects and challenges. Annu Rev Med. 2013;64:189-202. doi: 10.1146/annurev-med-120611-145115.
- Individual participant dataSharing planned: No
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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.
Aneesh Mehta, MD principal investigator
Emory University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Influenza Virus Vaccine Inactivated in people with Influenza and Influenza Immunisation, 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 12 inclusion and 13 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: stopped early, as of the sponsor's last update on 25 Oct 2023. 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.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Oct 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Percentage of Subjects Achieving Seroconversion (Pre-vaccination Hemagglutination Inhibition (HI) Titer <1:10 and a Post-vaccination HI Titer >1:40 or a Pre-vaccination HI Titer >1:10 and a Minimum Four-fold Rise in Post-vaccination HI Antibody Titer) (time frame: Day 28). The study lists 2 primary outcomes in all. 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 NCT02385123, which also lists 4 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 25 Oct 2023; AzTrials last refreshed its copy on 8 Nov 2026.