Influenza HA Ferritin Vaccine, Alone or in Prime-Boost Regimens With an Influenza DNA Vaccine in Healthy Adults
Condition: Influenza
MeSH terms: Influenza, Human
Intervention: VRC-FLUNPF081-00-VP (HA-F A/Sing); VRC-FLUDNA082-00-VP (DNA A/Sing)
Intervention description: VRC-FLUNPF081-00-VP (HA-F A/Sing) is an investigational influenza HA ferritin vaccine.; VRC-FLUDNA082-00-VP (DNA A/Sing) is an investigational influenza plasmid DNA vaccine.
Phase: Phase 1
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Enrollment: 50.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Flu Virus; Flu Shot; H2N2; Protein; Immune Response

Summary:

      Background:

      Influenza, or "flu", is a very common infectious respiratory disease. Researchers want to
      develop a vaccine against flu. Vaccines teach the body to fight or prevent an infection. When
      the body learns to fight an infection, this is called an immune response. In this study,
      researchers want to test two new vaccines to help the body make an immune response to flu.

      Subjects received the vaccine injections in the upper arm muscle. One vaccine, the influenza
      HA Ferritin vaccine (HA-F A/Sing), was given to all subjects with a needle injection. The
      other vaccine, influenza DNA vaccine (DNA A/Sing), was given to subjects in Group 3 by a
      needle-free device that uses high pressure to push the vaccine through the skin and into the
      muscle.

      Objective:

      To test the safety and side effects of two new vaccines for prevention of H2 influenza (flu).

      Eligibility:

      Part I: Healthy adults ages 18-47 born after 1969.

      Part II: Healthy adults ages 18-70, but not born in 1966-1969.

      Design:

      Volunteers were tested for eligibility in a separate screening protocol.

      In Part I, all subjects received injections of HA Ferritin vaccine. These subjects were not
      expected to have H2N2 exposure based on their age and when H2N2 last circulated in the
      population. Five subjects in Group 1 received one injection of 20 mcg dose vaccine at Day 0
      to test if it is safe. Then, five additional subjects in Group 2 received a total of two
      injections of a 60 mcg dose on Day 0 and 16 weeks later.

      In Part II, responses were evaluated from adults born before 1966 who may have prior
      potential exposure to H2N2 influenza as well as adults similar to those enrolled in Part I
      who are not expected to have H2N2 exposure. Also, Part II compared responses to 2 different
      vaccine regimens. Group 3 subjects received a DNA influenza vaccine prime at Day 0 and the HA
      Ferritin vaccine boost 16 weeks later. Group 4 subjects received the HA Ferritin vaccine 2
      times, on Day 0 and 16 weeks later.
    

Eligibility criteria:

        INCLUSION CRITERIA:

        A subject must meet all of the following criteria:

          -  Healthy subjects aged 18-70 (excluding subjects born between 1966-1969)

          -  Based on history and examination, must be in good general health and without history
             of any of the conditions listed in the exclusion criteria

          -  Received at least one licensed current seasonal influenza vaccine from 2014 to the
             present

          -  Able and willing to complete the informed consent process

          -  Available for clinic visits for 40 weeks after enrollment

          -  Willing to have blood samples collected, stored indefinitely, and used for research
             purposes

          -  Able to provide proof of identity to the satisfaction of the study clinician
             completing the enrollment process

          -  Physical examination and laboratory results without clinically significant findings
             and a Body Mass Index (BMI) less than or equal to 40 within the 84 days before
             enrollment

        Laboratory Criteria within 84 days before enrollment:

          -  White blood cells (WBC) and differential either within institutional normal range or
             accompanied by the site Principal Investigator (PI) or designee approval

          -  Total lymphocyte count greater than or equal to 800 cells/mm^3

          -  Platelets = 125,000 - 500,000/mm^3

          -  Hemoglobin within institutional normal range

          -  Serum iron either within institutional normal range or accompanied by the site PI or
             designee approval

          -  Alanine aminotransferase (ALT) less than or equal to 1.25 times institutional upper
             limit of normal (ULN)

          -  Aspartate aminotransferase (AST) less than or equal to 1.25 times institutional ULN

          -  Alkaline phosphatase (ALP) less than or equal to 1.1 times institutional ULN

          -  Total bilirubin within institutional ULN

          -  Serum creatinine less than or equal to 1.1 times institutional ULN

          -  Negative for HIV infection by an FDA approved method of detection

        Criteria applicable to women of childbearing potential:

          -  Negative beta-human chorionic gonadotropin (Beta-HCG) pregnancy test (urine or serum)
             on the day of enrollment

          -  Agrees to use an effective means of birth control from at least 21 days prior to
             enrollment through the end of the study

        EXCLUSION CRITERIA:

        A subject will be excluded if one or more of the following conditions apply:

        - Breast-feeding or planning to become pregnant during the study.

        Subject has received any of the following substances:

          -  More than 10 days of systemic immunosuppressive medications or cytotoxic medications
             within the 4 weeks prior to enrollment or any within the 14 days prior to enrollment

          -  Blood products within 16 weeks prior to enrollment

          -  Live attenuated vaccines within 4 weeks prior to enrollment

          -  Inactivated vaccines within 2 weeks prior to enrollment.

          -  Investigational research agents within 4 weeks prior to enrollment or planning to
             receive investigational products while on the study

          -  Current allergy treatment with allergen immunotherapy with antigen injections, unless
             on maintenance schedule

          -  Current anti-tuberculosis (TB) prophylaxis or therapy

          -  Previous H2 influenza investigational vaccine

          -  Receipt of a licensed influenza vaccine within 6 weeks before trial enrollment

        Subject has a history of any of the following clinically significant conditions:

          -  Serious reactions to vaccines that preclude receipt of study vaccinations as
             determined by the investigator

          -  Hereditary angioedema, acquired angioedema, or idiopathic forms of angioedema

          -  Asthma that is not well controlled

          -  Diabetes mellitus (type I or II), with the exception of gestational diabetes

          -  Thyroid disease that is not well controlled

          -  Idiopathic urticaria within the past year

          -  Evidence of autoimmune disease or immunodeficiency

          -  Hypertension that is not well controlled

          -  Bleeding disorder diagnosed by a doctor (e.g. factor deficiency, coagulopathy, or
             platelet disorder requiring special precautions) or significant bruising or bleeding
             difficulties with IM injections or blood draws

          -  Malignancy that is active or history of malignancy that is likely to recur during the
             period of the study.

          -  Seizure disorder other than 1) febrile seizures, 2) seizures secondary to alcohol
             withdrawal more than 3 years ago, or 3) seizures that have not required treatment
             within the last 3 years

          -  Asplenia, functional asplenia or any condition resulting in the absence or removal of
             the spleen

          -  Guillain-Barre Syndrome

          -  Psychiatric condition that precludes compliance with the protocol; past or present
             psychoses; or within 5 years prior to enrollment, a history of suicide plan or attempt

          -  Any medical, psychiatric, social condition, occupational reason or other
             responsibility that, in the judgment of the investigator, is a contraindication to
             protocol participation or impairs a subject's ability to give informed consent.