InfluenzaPhase 4NCT02485639

Analysis of Bone Marrow and Blood B Cell Immune Responses to Influenza Vaccination

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.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

This was a Phase IV open label and single arm study, with the aim of enrolling up to 55 healthy males and non-pregnant females in a single site, age 18-49 years old, inclusive. This study was designed to assess the humoral response to influenza vaccination and the longevity of humoral immunity to influenza vaccination… 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: 27 participants
Where: 1 siteUnited States
Study dates: 23 Dec 2015to 31 Mar 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 non-pregnant 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.
Safety labs:
White blood cell count (WBC), within reference range of lower limit of normal of 4,000 per microliter (uL), and upper limit of normal of 10,000 per microliter (uL).
Hemoglobin, within reference range of lower limit of normal of 11.4 grams per deciliter (gm/dL) and upper limit of normal of 16.1 grams per deciliter (gm/dL).

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Hematocrit, within reference range of lower limit of normal of 33.3 percent and an upper limit of normal of 46.5 percent.
Platelet Count, within reference range of lower limit of normal of 150,000 per microliter (uL) and upper limit of normal of 400,000 per microliter (uL).
Prothrombin Time (PT/INR), PT below or equal to the upper limit of normal of 13.1 seconds; International Normalized Ratio (INR) within normal reference range of less than 1.5 (normal range for non-anti-coagulated patients).
Creatinine within reference range of lower limit of normal of 0.4 milligrams per deciliter (mg / dL) and upper limit of normal of 1.2 milligrams per deciliter (mg / dL).
Potassium, within reference range of lower limit of normal of 3.6 millimolar (mM) and upper limit of normal of 5.1 millimolar (mM).
Heart rate > / = 55 to < / = 100 per minute.
Systolic blood pressure > / = 90 to < / = 150 millimeters of mercury (mmHg).
Diastolic blood pressure < 90 millimeters of mercury (mmHg).
Oral temperature < 100 degrees Fahrenheit.
Respirations even, unlabored, and > 10 / minute to < 20 / minute.
Female subjects of child bearing potential must have a negative urine pregnancy test at the screening visit, enrollment visit and prior to subsequent bone marrow aspirate procedures. Female subjects of childbearing potential must agree to practice abstinence, use a barrier method of birth control, or use an U.S. Food and Drug Administration (FDA) approved form of birth control.
Subjects who have not received seasonal flu vaccine for the current year (September - June).

Who cannot join

If female, active pregnancy or breast-feeding or plans to become pregnant during study participation.
Subject report of having 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 acute or 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.
Subject report of taking anticoagulants, or long-term (greater than 14 days) systemic steroids or other immunosuppressive medications.
Subject report of known allergy to lidocaine.
Subject report of known hypersensitivity or allergy to eggs, egg or chicken protein, report of allergy to components of the study vaccine or other components of the study vaccine.
Subject report of known latex allergy.

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Subject report of a history of severe reactions following previous immunization with licensed or unlicensed influenza virus vaccines.
Subject report of a history of Guillain-Barre syndrome.
Subjects who believe they cannot tolerate the bone marrow aspirations without sedation.
Subjects with an active infection or that have an acute illness within 72 hours prior to study vaccination. Subject having had 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.
Subjects who are participating in another clinical trial involving the use of investigational agents or vaccines.

Trial locations and contacts

1 site in 1 country.

United States1 site

Emory Clinic - Winship Cancer Institute
Atlanta, Georgia, 30322-1059

Other trials in United States

About this study

This was a multi-year study. After one year of participation, participants were offered the opportunity to participate in the study for up to 3 consecutive years, provided eligibility criteria was met each year. Participants who elected to continue in the study after first year of participation were rescreened to verify continued eligibility and re-consented prior to subsequent participation. The primary study objective was to investigate the longevity of humoral immunity to influenza virus in humans.

Note: Due to the Coronavirus Disease of 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. Participant visits for Day 7 and Day 14 were not impacted. For this study, there were participants whose Day 28 and Day 90 visits were impacted by the temporary halting of non-essential research studies. As such, a request was submitted to the Emory University Institutional Review Board to extend the missed visit windows for the Day 28 and Day 90 visits for a maximum of up to 180 days, to ensure that ample time was available to bring participants back for their missed visits. Enrollment for this study ended on March 31, 2020, before research activities could resume at Emory.

Read the detailed description

The laboratory technique used in this study characterized persistence and clonotype of antigen specific B-cells and plasmablasts in blood and bone marrow. Enrolled participants received licensed seasonal inactivated influenza vaccine (administered as a part of the study). The vaccine was administered according to the package insert, and study participants donated serial samples of blood and bone marrow aspirate for immunology monitoring.

Safety was assessed from the time of study enrollment through the last study visit, via monitoring of vital signs, change in health status, and targeted physical exam with safety labs prior to each bone marrow aspirate procedure. Repeated measurements of humoral immunity were obtained at 7 days, 14 days, 28 days, 90 days and at one year post-vaccination to assess the magnitude, clonal diversity and persistence of B-cell responses to influenza vaccination.

Re-enrolling participants received new subject identifiers and will count towards the total enrollment number for subsequent years of participation. A separate subject record will be maintained each year a subject re-enrolls in the study. Enrollment for the next year will begin with the availability of the seasonal flu vaccine. For participants who elect to re-enroll in the study, the Day 365 visit (+/- 3 month window) would also be the Day 0 visit for the subsequent year. The primary study objective is to investigate the longevity of humoral immunity to influenza virus in humans. The secondary study objective is the longitudinal tracking of vaccine-induced B cell responses with special emphasis on broadly neutralizing HA (hemagglutinin) stem-reactive responses.

Note: Due to the Coronavirus Disease of 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. Participant visits for Day 7 and Day 14 were not impacted. For this study, there are participants whose Day 28 and Day 90 visits were impacted by the temporary halting of non-essential research studies. As such, a request was submitted to the Emory University Institutional Review Board to extend the missed visit windows for the Day 28 and Day 90 visits for a maximum of up to 180 days, to ensure that ample time was available to bring participants back for their missed visits. Enrollment for this study ended on March 31, 2020, before research activities could resume at Emory.

Conditions: Influenza, Influenza Immunisation
Being tested: Influenza Virus Vaccine Inactivated
Keywords: HA (hemagglutinin) -specific plasmablasts, humoral immunity, influenza, memory B cells
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. All participants received vaccine intramuscularly (IM) on Day 0.

Study groups in NCT02485639
Study group	Role	What they receive
Influenza Virus Vaccine Inactivated	Experimental	All study participants received licensed inactivated influenza vaccine intramuscularly (IM) on Day 0. Receives: Biological: Influenza Virus Vaccine Inactivated

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of Influenza-specific Antibody Secreting Cells (ASC) Present in the Blood
Blood Immunoglobulin G (IgG) ASC specific for the seasonal influenza vaccine were measured by enzyme-linked immunosorbent spot (ELISPOT) using vaccine-coated plates. Numbers of influenza-specific ASC per million peripheral blood mononuclear cells are reported.
Measured: Day 7
Number of Influenza-specific Antibody Secreting Cells (ASC) Present in the Bone Marrow
Influenza-specific IgG ASC and total IgG ASC were measured in bone marrow samples by ELISPOT using plates coated with influenza vaccine or total IgG capture antibody. Influenza-specific bone marrow IgG ASC numbers are expressed as a percentage of the total bone marrow IgG ASC number.
Measured: Day 0
Number of Influenza-specific Antibody Secreting Cells (ASC) Present in the Bone Marrow
Influenza-specific IgG ASC and total IgG ASC were measured in bone marrow samples by ELISPOT using plates coated with influenza vaccine or total IgG capture antibody. Influenza-specific bone marrow IgG ASC numbers are expressed as a percentage of the total bone marrow IgG ASC number.
Measured: Day 28
Number of Influenza-specific Antibody Secreting Cells (ASC) Present in the Bone Marrow
Influenza-specific IgG ASC and total IgG ASC were measured in bone marrow samples by ELISPOT using plates coated with influenza vaccine or total IgG capture antibody. Influenza-specific bone marrow IgG ASC numbers are expressed as a percentage of the total bone marrow IgG ASC number.
Measured: Day 365
Number of Influenza-specific Memory B Cells Present in the Blood
Influenza-specific memory B cells were assayed by ELISPOT after polyclonal stimulation of peripheral blood mononuclear cells to generate ASC. The influenza-specific memory B cell frequencies are reported as the percentage of IgG secreting cells found in the stimulated cultures.
Measured: Day 0
Number of Influenza-specific Memory B Cells Present in the Blood
Influenza-specific memory B cells were assayed by ELISPOT after polyclonal stimulation of peripheral blood mononuclear cells to generate ASC. The influenza-specific memory B cell frequencies are reported as the percentage of IgG secreting cells found in the stimulated cultures.
Measured: Day 28
Number of Influenza-specific Memory B Cells Present in the Blood
Influenza-specific memory B cells were assayed by ELISPOT after polyclonal stimulation of peripheral blood mononuclear cells to generate ASC. The influenza-specific memory B cell frequencies are reported as the percentage of IgG secreting cells found in the stimulated cultures.
Measured: Day 365
Number of Subjects Who Initially Seroconverted and Maintained Seroconversion at 1 Year Post Vaccination
Initial seroconversion is defined as having a pre-vaccination (day 0) hemagglutination inhibition (HAI) titer < 1:40 against a particular strain and a day 28 post-vaccination titer > / = 1:40 against the same strain OR a pre-vaccination HAI titer >1:40 and an increase in titer of at least 4-fold on day 28 relative to day 0. Maintenance of seroconversion in those who initially seroconverted is defined as maintaining an HAI titer >/= 40 at 1 year in those with day 0 titers < 40 OR maintaining a >/= 4-fold increase in HAI titer at one year compared to day 0.
HAI assays were performed using 0.75% guinea pig red blood cells and virus stocks matched to the strains in the vaccines received by each donor.
Measured: Day 365
Number of Subjects Achieving Seroconversion to Each of the Strains in the Vaccine
Seroconversion defined as having a pre-vaccination (day 0) hemagglutination inhibition (HAI) titer < 1:40 against a particular strain and a Day 28 post-vaccination titer > / = 1:40 against the same strain OR a pre-vaccination HAI titer >1:40 and an increase in titer of at least 4-fold on day 28. HAI assays were performed using 0.75% guinea pig red blood cells and virus stocks matched to the strains in the vaccines received by each donor.
Measured: Day 28

Secondary outcomes (2)

Frequency of Hemagglutinin Stem Reactive Responses to Influenza Vaccine Among Blood Plasmablasts
Blood IgG ASC specific for the seasonal influenza vaccine were measured by ELISPOT using plates coated with chimeric hemagglutinin antigen containing the pandemic H1 stem domain fused to the head domain of an H9 influenza virus. Numbers of stem-specific ASC per million peripheral blood mononuclear cells are reported.
Measured: Day 7
Frequency of Hemagglutinin Stem Reactive Responses to Influenza Vaccine Among the Bone Marrow Plasma Cells
Influenza-specific IgG ASC and total IgG ASC were measured in bone marrow samples by ELISPOT using plates coated with H9 head/H1 stem chimeric hemagglutinin antigen or total IgG capture antibody. Stem-specific bone marrow IgG ASC numbers are expressed as a percentage of the total bone marrow IgG ASC number.
Measured: Day 365

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

23 Dec 201531 Mar 2020

First posted30 Jun 2015 (estimated)
Study start23 Dec 2015
Primary completion31 Mar 2020
Study completion31 Mar 2020

Why it stopped: Study was terminated due to CoronaVIrus Disease of 2019 (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 (6)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: 27 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02485639
Sponsor's protocol ID: 14-0059
Other IDs: HHSN272201400004C
Status last verified: Mar 2021
First submitted: 11 Jun 2015
Last updated: 24 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 12517228
Centers 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 24048214
Kunzel 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 8911005
Pica 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
Wrammert J, Smith K, Miller J, Langley WA, Kokko K, Larsen C, Zheng NY, Mays I, Garman L, Helms C, James J, Air GM, Capra JD, Ahmed R, Wilson PC. Rapid cloning of high-affinity human monoclonal antibodies against influenza virus. Nature. 2008 May 29;453(7195):667-71. doi: 10.1038/nature06890. Epub 2008 Apr 30.
PubMed 18449194
Slifka MK, Antia R, Whitmire JK, Ahmed R. Humoral immunity due to long-lived plasma cells. Immunity. 1998 Mar;8(3):363-72. doi: 10.1016/s1074-7613(00)80541-5.
PubMed 9529153

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 24 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Analysis of Bone Marrow and Blood B Cell Immune Responses to Influenza Vaccination
ClinicalTrials.gov ID: NCT02485639
Acronym / sponsor ID: 14-0059
Conditions: Influenza, Influenza Immunisation
Keywords: HA (hemagglutinin) -specific plasmablasts, humoral immunity, influenza, memory B cells
Phase: Phase 4
Study type: Interventional
Recruitment status: TerminatedReason stopped: Study was terminated due to CoronaVIrus Disease of 2019 (COVID-19) pandemic.
Enrolment: 27 participants (actual)
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
Study start: 23 Dec 2015 (actual)
Primary completion: 31 Mar 2020 (actual)
Study completion: 31 Mar 2020 (actual)
First posted: 30 Jun 2015 (estimated)
Results: Posted 24 Oct 2023

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Note: Due to the Coronavirus Disease of 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. Participant visits for Day 7 and Day 14 were not impacted. For this study, there are participants whose Day 28 and Day 90 visits were impacted by the temporary halting of non-essential research studies. As such, a request was submitted to the Emory University Institutional Review Board to extend the missed visit windows for the Day 28 and Day 90 visits for a maximum of up to 180 days, to ensure that ample time was available to bring participants back for their missed visits. Enrollment for this study ended on March 31, 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
Influenza Virus Vaccine Inactivated	Experimental	Biological: Influenza Virus Vaccine InactivatedAll study participants received licensed inactivated influenza vaccine intramuscularly (IM) on Day 0.

Who may qualify

Ages: 18 to 49 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (18 listed)

Male or non-pregnant 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.
Safety labs:
White blood cell count (WBC), within reference range of lower limit of normal of 4,000 per microliter (uL), and upper limit of normal of 10,000 per microliter (uL).

Key exclusion criteria (11 listed)

If female, active pregnancy or breast-feeding or plans to become pregnant during study participation.
Subject report of having 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 acute or 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.
Subject report of taking anticoagulants, or long-term (greater than 14 days) systemic steroids or other immunosuppressive medications.
Subject report of known allergy to lidocaine.
Subject report of known hypersensitivity or allergy to eggs, egg or chicken protein, report of allergy to components of the study vaccine or other components of the study vaccine.

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. All participants received vaccine intramuscularly (IM) on Day 0.	Biological	Influenza Virus Vaccine Inactivated

Primary outcome

Number of Influenza-specific Antibody Secreting Cells (ASC) Present in the Blood
Time frame: Day 7
Blood Immunoglobulin G (IgG) ASC specific for the seasonal influenza vaccine were measured by enzyme-linked immunosorbent spot (ELISPOT) using vaccine-coated plates. Numbers of influenza-specific ASC per million peripheral blood mononuclear cells are reported.
Number of Influenza-specific Antibody Secreting Cells (ASC) Present in the Bone Marrow
Time frame: Day 0
Influenza-specific IgG ASC and total IgG ASC were measured in bone marrow samples by ELISPOT using plates coated with influenza vaccine or total IgG capture antibody. Influenza-specific bone marrow IgG ASC numbers are expressed as a percentage of the total bone marrow IgG ASC number.
Number of Influenza-specific Antibody Secreting Cells (ASC) Present in the Bone Marrow
Time frame: Day 28
Influenza-specific IgG ASC and total IgG ASC were measured in bone marrow samples by ELISPOT using plates coated with influenza vaccine or total IgG capture antibody. Influenza-specific bone marrow IgG ASC numbers are expressed as a percentage of the total bone marrow IgG ASC number.
Number of Influenza-specific Antibody Secreting Cells (ASC) Present in the Bone Marrow
Time frame: Day 365
Influenza-specific IgG ASC and total IgG ASC were measured in bone marrow samples by ELISPOT using plates coated with influenza vaccine or total IgG capture antibody. Influenza-specific bone marrow IgG ASC numbers are expressed as a percentage of the total bone marrow IgG ASC number.
Number of Influenza-specific Memory B Cells Present in the Blood
Time frame: Day 0
Influenza-specific memory B cells were assayed by ELISPOT after polyclonal stimulation of peripheral blood mononuclear cells to generate ASC. The influenza-specific memory B cell frequencies are reported as the percentage of IgG secreting cells found in the stimulated cultures.
Number of Influenza-specific Memory B Cells Present in the Blood
Time frame: Day 28
Influenza-specific memory B cells were assayed by ELISPOT after polyclonal stimulation of peripheral blood mononuclear cells to generate ASC. The influenza-specific memory B cell frequencies are reported as the percentage of IgG secreting cells found in the stimulated cultures.
Number of Influenza-specific Memory B Cells Present in the Blood
Time frame: Day 365
Influenza-specific memory B cells were assayed by ELISPOT after polyclonal stimulation of peripheral blood mononuclear cells to generate ASC. The influenza-specific memory B cell frequencies are reported as the percentage of IgG secreting cells found in the stimulated cultures.
Number of Subjects Who Initially Seroconverted and Maintained Seroconversion at 1 Year Post Vaccination
Time frame: Day 365
Initial seroconversion is defined as having a pre-vaccination (day 0) hemagglutination inhibition (HAI) titer < 1:40 against a particular strain and a day 28 post-vaccination titer > / = 1:40 against the same strain OR a pre-vaccination HAI titer >1:40 and an increase in titer of at least 4-fold on day 28 relative to day 0. Maintenance of seroconversion in those who initially seroconverted is defined as maintaining an HAI titer >/= 40 at 1 year in those with day 0 titers < 40 OR maintaining a >/= 4-fold increase in HAI titer at one year compared to day 0. HAI assays were performed using 0.75% guinea pig red blood cells and virus stocks matched to the strains in the vaccines received by each donor.
Number of Subjects Achieving Seroconversion to Each of the Strains in the Vaccine
Time frame: Day 28
Seroconversion defined as having a pre-vaccination (day 0) hemagglutination inhibition (HAI) titer < 1:40 against a particular strain and a Day 28 post-vaccination titer > / = 1:40 against the same strain OR a pre-vaccination HAI titer >1:40 and an increase in titer of at least 4-fold on day 28. HAI assays were performed using 0.75% guinea pig red blood cells and virus stocks matched to the strains in the vaccines received by each donor.

2 secondary outcomes

Frequency of Hemagglutinin Stem Reactive Responses to Influenza Vaccine Among Blood Plasmablasts
Time frame: Day 7
Frequency of Hemagglutinin Stem Reactive Responses to Influenza Vaccine Among the Bone Marrow Plasma Cells
Time frame: Day 365

Results and safety

Results posted to the registry on 24 Oct 2023, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Influenza Virus Vaccine - Inactivated	27	11

Primary outcome: Number of Influenza-specific Antibody Secreting Cells (ASC) Present in the Blood

Time frame: Day 7. Geometric mean (Inter-Quartile Range). Unit: Number of Influenza-specific ASC/million

Measure	Influenza Virus Vaccine - Inactivated n = 24
Value	284.2 (81.8 to 501.2)

Population analysed: Of the 27 donors enrolled in this study, 24 participants were included in this analysis, as one participant withdrew from the study prior to the Day 7 sample collection, one participant had a failed ELISPOT assay/bad plate batch, and for the remaining donor, a sample was not collected at this time-point, as the donor missed their appointment.

Primary outcome: Number of Influenza-specific Antibody Secreting Cells (ASC) Present in the Bone Marrow

Time frame: Day 0. Geometric mean (Inter-Quartile Range). Unit: Percent of total BM IgG ASC number

Measure	Influenza Virus Vaccine - Inactivated n = 15
Value	1.08 (0.79 to 1.71)

Population analysed: Of the 27 donors enrolled in this study, 15 donors were eligible to have their samples analyzed for this Day 0 time-point outcome measure. 15 participants were analyzed for this time-point outcome measure as due to limited bone marrow yields, as ELISPOT assays were not run on every bone marrow sample. This was the case for 12 of the donors for this time-point outcome measure.

Primary outcome: Number of Influenza-specific Antibody Secreting Cells (ASC) Present in the Bone Marrow

Time frame: Day 28. Geometric mean (Inter-Quartile Range). Unit: Percent of total BM IgG ASC number

Measure	Influenza Virus Vaccine - Inactivated n = 9
Value	3.49 (2.19 to 3.75)

Population analysed: Of the 27 donors enrolled in this study, 9 donors were eligible to have their samples analyzed for this Day 28 time-point outcome measure. Due to limited bone marrow yields, ELISPOT assays were not run on every bone marrow sample. This was the case for 14 of the donors for this time-point measure. There were two donor/participant withdrawals prior to the Day 28 time-point collection, and two donors were unable to provide a sample, as their lab values were out of range for the bone marrow draw.

Primary outcome: Number of Influenza-specific Antibody Secreting Cells (ASC) Present in the Bone Marrow

Time frame: Day 365. Geometric mean (Inter-Quartile Range). Unit: Percent of total BM IgG ASC number

Measure	Influenza Virus Vaccine - Inactivated n = 7
Value	1.48 (1.24 to 1.78)

Population analysed: Of the 27 donors enrolled in this study, seven donors were eligible to have their samples analyzed for this Day 365 time-point outcome measure. Due to limited bone marrow yields, ELISPOT assays were not run on every bone marrow sample. This was the case for three of the donors for this time-point outcome measure. There were nine donor/participant withdrawals prior to the Day 365 time-point collection. Eight Day 365 visits were halted due to COVID, and samples could not be collected.

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: 1 year Adverse event data were collected from Day 0 (enrollment) to Day 365 (the end of follow-up). Adverse event data were collected at each of the follow-up visits (Day 7, Day 14, Day 28, Day 90, and Day 365).. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Influenza Virus Vaccine Inactivated	0 of 27 (0%)	1 of 27 (3.7%)	0 of 27

Limitations and caveats (from the sponsor): Due to the COVID-19 pandemic, all non-essential research was halted at our site (mid-March 2020). New enrollments and follow-up visits were halted, impacting participants' follow-up visits. One Day 28 visit was halted, three Day 90 visits were halted. Seven Day 365 visits were halted. We requested an expansion of the visit windows, however, enrollment for this study ended on March 31, 2020, before research activities could resume at Emory.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 24 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.
Background: PubMed 18449194Wrammert J, Smith K, Miller J, Langley WA, Kokko K, Larsen C, Zheng NY, Mays I, Garman L, Helms C, James J, Air GM, Capra JD, Ahmed R, Wilson PC. Rapid cloning of high-affinity human monoclonal antibodies against influenza virus. Nature. 2008 May 29;453(7195):667-71. doi: 10.1038/nature06890. Epub 2008 Apr 30.
Background: PubMed 9529153Slifka MK, Antia R, Whitmire JK, Ahmed R. Humoral immunity due to long-lived plasma cells. Immunity. 1998 Mar;8(3):363-72. doi: 10.1016/s1074-7613(00)80541-5.
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.

Edmund K Waller, MD, PhD 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?

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 18 inclusion and 11 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 24 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 24 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?

Number of Influenza-specific Antibody Secreting Cells (ASC) Present in the Blood (time frame: Day 7). The study lists 9 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 NCT02485639, which also lists 6 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 24 Oct 2023.