Dose, Safety, Tolerability and Immunogenicity of an Influenza H10 Stabilized Stem Ferritin Vaccine, VRC-FLUNPF0103-00-VP, in Healthy Adults
Condition: Influenza
MeSH terms: Influenza, Human
Intervention: VRC-FLUNPF0103-00-VP (H10ssF-6473)
Intervention description: The vaccine is composed of the haemagglutinin (HA) stem domain from A/Jiangxi/IPB13/2013 (H10N8) influenza genetically fused to the ferritin protein from H. pylori. Purified H10ssF-6473 displays eight well-formed HA trimers that antigenically resemble the native H10 stem viral spikes.
Phase: Phase 1
Study type: Interventional
Primary purpose: Prevention
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Intervention model description: Dose escalation study
Masking: None (Open Label)
Enrollment: 25.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Flu Virus; Respiratory Illness; Viral Infection; Experimental Vaccine

Summary:

      Background: The flu is a common viral infection that can be deadly for certain people.
      Vaccines against flu have been developed to teach the body to prevent or fight the infection.
      A new vaccine may help the body to make an immune response to H10 flu, a flu strain that
      infects humans.

      Objective:

      To test the safety and effectiveness of the H10 Stabilized Stem Ferritin vaccine
      (VRC-FLUNPF0103-00-VP or H10ssF-6473).

      Eligibility:

      Healthy adults ages 18-70, but not born between 1965-1970

      Design:

      Participants received 1 or 2 vaccinations by injections (shots) in the upper arm muscle over
      4 months. Participants received a thermometer and recorded their temperature and symptoms
      every day on/with/via a diary card for 7 days after each injection. The injection site was
      checked for redness, swelling, itching or bruising.

      Participants had 8-10 follow-up visits over 10 months. At follow-up visits, participants had
      blood drawn and were checked for health changes or problems. Participants who reported
      influenza-like illness had nose and throat swabs collected for evaluation of viral infection.

      Some participants had apheresis. A needle was placed into a vein in both arms. Blood was
      removed through a needle in the vein of one arm. A machine removed the white blood cells and
      then the rest of the blood was returned to the participant through a needle in the other arm.
    

Eligibility criteria:

        INCLUSION CRITERIA:

          1. Healthy adults between the ages of 18-70 years (excluding adults born between January
             1, 1965 and December 31,1970)

          2. Based on history and examination, in good general health and without history of any of
             the conditions listed in the exclusion criteria

          3. Received at least one licensed influenza vaccine from 2015 to the present

          4. Able and willing to complete the informed consent process

          5. Available for clinic visits for 40 weeks after enrollment

          6. Able to provide proof of identity to the satisfaction of the study clinician
             completing the enrollment process

          7. Physical examination and laboratory results without clinically significant findings
             and a Body Mass Index (BMI) less than or equal to 40 within the 56 days before
             enrollment

             Laboratory Criteria within 56 days before enrollment

          8. White blood cells (WBC) and differential within institutional normal range or
             accompanied by the site Principal Investigator (PI) or designee approval

          9. Total lymphocyte count greater than or equal to 800 cells/microL

         10. Platelets = 125,000 - 500,000 cells/microL

         11. Hemoglobin within institutional normal range or accompanied by the PI or designee
             approval

         12. Serum iron within institutional normal range or accompanied by the site PI or designee
             approval

         13. Serum ferritin within institutional normal range or accompanied by the site PI or
             designee approval

         14. Alanine aminotransferase (ALT) less than or equal to 1.25 x institutional upper limit
             of normal (ULN)

         15. Aspartate aminotransferase (AST) less than or equal to 1.25 x institutional ULN

         16. Alkaline phosphatase (ALP) <1.1 x institutional ULN

         17. Total bilirubin within institutional normal range, except when otherwise consistent
             with Gilbert's syndrome

         18. Serum creatinine less than or equal to 1.1 x institutional ULN

         19. Negative for HIV infection by an FDA-approved method of detection

             Criteria applicable to women of childbearing potential:

         20. Negative beta-human chorionic gonadotropin (Beta-HCG) pregnancy test (urine or serum)
             on the day of enrollment

         21. 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:

          1. Breast-feeding or planning to become pregnant during the study

             Individual has received any of the following substances:

          2. 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

          3. Blood products within 16 weeks prior to enrollment

          4. Live attenuated vaccines within 4 weeks prior to enrollment

          5. Inactivated vaccines within 2 weeks prior to enrollment

          6. Investigational research agents within 4 weeks prior to enrollment or planning to
             receive investigational products while on the study

          7. Current allergy treatment with allergen immunotherapy with antigen injections, unless
             on maintenance schedule

          8. Current anti-TB (tuberculosis) prophylaxis or therapy

          9. Previous investigational H10 influenza vaccine

         10. Receipt of a licensed influenza vaccine within 6 weeks prior to enrollment

             Individual has a history of any of the following clinically significant conditions:

         11. Serious reactions to vaccines that preclude receipt of the study vaccination as
             determined by the investigator

         12. Hereditary angioedema, acquired angioedema, or idiopathic forms of angioedema

         13. Asthma that is not well controlled

         14. Diabetes mellitus (type I or II), with the exception of gestational diabetes

         15. Thyroid disease that is not well controlled

         16. Idiopathic urticaria within the past year

         17. Autoimmune disease or immunodeficiency

         18. Hypertension that is not well controlled (baseline systolic > 140 mmHg or diastolic >
             90 mmHg)

         19. 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

         20. Malignancy that is active or history of malignancy that is likely to recur during the
             period of the study

         21. 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

         22. Asplenia, functional asplenia or any condition resulting in the absence or removal of
             the spleen

         23. Guillain-Barre Syndrome

         24. Previous or current infection with severe acute respiratory syndrome coronavirus 2
             (SARS-CoV-2) documented by polymerase chain reaction (PCR) test

         25. 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 participant's ability to give informed consent.

        INCLUSION OF VULNERABLE PARTICIPANTS

        Children

        Children were not eligible to participate in this clinical trial because the
        investigational vaccine had not been previously evaluated in adults. If the product is
        assessed as safe and immunogenic, other protocols designed for children may be conducted in
        the future.

        NIH Employees

        NIH employees and members of their immediate families could have participated in this
        protocol. If eligible, the Guidelines for the Inclusion of Employees in NIH Research
        Studies were followed for employees and each employee was given a copy of the 'NIH
        Information Sheet on Employee Research Participation' and a copy of the 'Leave Policy for
        NIH Employees Participating in NIH Medical Research Studies.'

        Neither participation nor refusal to participate had an effect, either beneficial or
        adverse, on the participant's employment or work situation. The NIH information sheet
        regarding NIH employee research participation was distributed to all potential participants
        who are NIH employees. The employee participant's privacy and confidentiality was preserved
        in accordance with NIH Clinical Center and NIAID policies. For NIH employee participants,
        consent was obtained by an individual who is independent of the participant's team. If the
        individual obtaining consent is a co-worker to the participant, independent monitoring of
        the consent process will be included through the Bioethics Consultation Service. Protocol
        study staff were trained on obtaining potentially sensitive and private information from
        co-workers or subordinates.