Influenza HA Ferritin Vaccine, Alone or in Prime-Boost Regimens With an Influenza DNA Vaccine in Healthy Adults
Condition: Influenza
MeSH terms: Influenza, Human
Study type: Interventional
Phase: Phase 1

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.
    

Detailed description: 
      Study Design: This is a Phase I open-label, dose escalation study to evaluate the dose,
      safety, tolerability, and immunogenicity of VRC-FLUNPF081-00-VP (HA-F A/Sing) vaccine alone
      or in prime-boost regimens with VRC-FLUDNA082-00-VP (DNA A/Sing) vaccine. The hypotheses are
      that VRC-FLUNPF081-00-VP and VRC-FLUDNA082-00-VP vaccines are safe, well-tolerated, and
      induce an immune response to the H2 antigen. The primary objectives are to evaluate the
      safety and tolerability of two different doses of the HA-F A/Sing vaccine alone and in
      prime-boost regimens in healthy adults. Secondary objectives are related to the evaluation of
      the immunogenicity of the HA-F A/Sing and DNA A/Sing vaccines in prime-boost regimens.

      Study Products: The investigational HA-F A/Sing vaccine, developed by the Vaccine Research
      Center (VRC), National Institute of Allergy and Infectious Diseases (NIAID), is composed of
      Helicobacter pylori non-haem ferritin with an influenza virus H2 hemagglutinin (HA) insert to
      form a nanoparticle displaying eight HA trimers from A/Singapore/1/57 (H2N2) influenza.

      The investigational DNA A/Sing vaccine, developed by the VRC, NIAID, is composed of a single
      closed-circular DNA plasmid that encodes the H2 protein of A/Singapore/1/57 influenza.

      Subjects: Up to 80 healthy adults ages 18-70 were enrolled; adults born between 1966 and 1969
      were excluded from the trial.

      Study Plan: Vaccines were administered intramuscularly (IM) in the deltoid muscle. This study
      has two parts:

      Part I evaluated the safety, tolerability, and immunogenicity of 1 or 2 doses of the HA-F
      A/Sing vaccine in a dose-escalation design. In Group 1, five subjects received a 20 mcg dose
      of the HA-F A/Sing vaccine via needle and syringe on Day 0. If this dose was assessed as safe
      and well tolerated, enrollment began for Group 2. In Group 2, five subjects received the
      higher 60 mcg dose of the HA-F A/Sing vaccine via needle and syringe on Day 0 and Week 16. If
      this higher dose was assessed as safe, enrollment began for Part II.

      Part II evaluated the safety, tolerability, and immunogenicity of HA-F A/Sing vaccine in
      prime-boost regimens. Subjects were stratified by age and randomized equally into Groups 3
      and Group 4. In Group 3, subjects received DNA A/Sing vaccine via a PharmaJet Needle-Free
      Injector on Day 0 and HA-F A/Sing vaccine via needle and syringe on Week 16. In Group 4,
      subjects received HA-F A/Sing vaccine via needle and syringe on Day 0 and Week 16.

      For Group 1, the protocol required about 8 clinic visits and 1 telephone follow up contact
      after the injection.

      For Group 2, Group 3 and Group 4, the protocol required about 10 clinic visits and 2
      telephone follow-up contacts after each injection.

      For all Groups, solicited reactogenicity were evaluated using a 7-day diary card. Assessment
      of vaccine safety included clinical observation and monitoring of hematological and chemical
      parameters at clinical visits throughout the study.

      Study Duration: Subjects were evaluated for 40 weeks following the first vaccine
      administration.
    

Intervention name(s): VRC-FLUNPF081-00-VP (HA-F A/Sing); VRC-FLUDNA082-00-VP (DNA A/Sing)
Intervention type(s): Biological; Biological
Intervention description(s): 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.
Allocation: Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Flu Virus; Flu Shot; H2N2; Protein; Immune Response