Analysis of Bone Marrow and Blood B Cell Immune Responses to Influenza Vaccination
Condition: Influenza; Influenza Immunisation
MeSH terms: Influenza, Human
Intervention: Influenza Virus Vaccine Inactivated
Intervention description: 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.
Phase: Phase 4
Study type: Interventional
Primary purpose: Prevention
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 27.0
Sex: All
Minimum age: 18 Years
Maximum age: 49 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: HA (hemagglutinin) -specific plasmablasts; humoral immunity; influenza; memory B cells

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 in healthy adults. Total enrollment was 27
      participants.

      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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  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).

          -  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).

        Exclusion Criteria:

          -  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.

          -  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.