Intranasal AD4-H5-VTN as an Adenovirus Vaccine
Condition: Healthy Volunteer
Study type: Interventional
Phase: Phase 1

Summary: 
      Background:

        -  Adenoviruses are viruses that typically cause symptoms of a cold or eye infection. These
           viruses are being tested as part of a possible new vaccine. Researchers hope that the
           adenovirus will help carry the vaccine into the body and cause an immune response. An
           immune response is the body s release of cells and substances that protect the body from
           infection. If an adenovirus vaccine can be developed, it might be used as part of a
           vaccine for malaria or other serious illnesses. Researchers want to test the adenovirus
           vaccine as a nasal spray in healthy volunteers. The vaccine is called AD4-H5-VTN.

        -  Because the vaccine contains a live adenovirus, there is a possibility that participants
           can infect other people. Therefore, participants' intimate contacts must join this
           study. An intimate contact is someone who the participant will kiss on the mouth or have
           sexual intercourse with during the period of this study.

      Objectives:

        -  To study the immune response of the AD4-H5-VTN vaccine in healthy volunteers.

        -  To see if the adenovirus in the AD4-H5-VTN vaccine is contagious or spreads to others.

      Eligibility:

        -  Healthy volunteers between 18 and 49 years of age.

        -  Intimate contacts of healthy volunteers between 18 and 65 years of age.

        -  Participants must not have evidence of previous exposure to adenovirus type 4.

      Design:

        -  Participants will be screened with a physical exam and medical history. Blood and urine
           samples will be collected.

        -  Participants who will receive the vaccine must be willing to be hospitalized for between
           5 and 7 days. They will come to the National Institutes of Health for follow-up visits
           weekly for the first month, after 8 weeks, in 6 months, and possibly 1 year. They must
           also avoid all vaccines (including seasonal flu vaccine) and allergy shots for 30 days
           before and after having the study vaccine.

        -  Participants will enter the hospital for the vaccine study visit. They will receive the
           vaccine as a nasal spray. Because the vaccine uses a live virus, participants may be
           contagious for the virus for up to 4 weeks. They will remain in the hospital in
           respiratory isolation for 7 days, or until they have two negative nasal washes taken 1
           day apart. A negative nasal wash means that there is no live virus in the nose.

        -  After leaving the hospital, participants will keep a diary at home for at least 3 weeks.
           They will record their temperature, any symptoms, or other health changes every day
           during this time.

        -  Participants should avoid intimate contact with others for 28 days after having the
           vaccine. Intimate contact includes kissing on the mouth and sexual intercourse. Also,
           participants should not share kitchen utensils, drinking cups, towels, or hair combs
           with others. Intimate contacts will also keep track of any illnesses or symptoms they
           develop during this time.

        -  At the follow-up visits, participants will provide blood and swab samples for study.
    

Detailed description: 
      This is a Phase 1 single center, dose-escalation study designed to evaluate the safety and
      immunogenicity of live, replication competent recombinant Adenovirus type 4-H5N1 Influenza
      Vietnam 1194 Hemagglutinin (HA) (Ad4-H5-Vtn). Determining the optimal route and dose for this
      recombinant platform will greatly accelerate investigations of this vector as an influenza
      vaccine and an HIV vaccine platform.

      The primary goal of this study is to evaluate safety of ascending dosages of the Ad4-H5-Vtn
      vaccine following intranasal administration. A dosage will be selected to further evaluate
      the humoral, cellular, and mucosal immune responses against both the vector and the inserted
      gene. The Ad4-H5-Vtn will be initiated at 103 viral particles (vp). Once safety is
      established at the initial dose, a second round of testing will begin at the next ten-fold
      higher dose. The Ad4-H5-Vtn vaccine will be assessed in three participants at each dosage
      level. The maximum viral dose administered will be 108 vp.

      In addition to clinical and laboratory monitoring of safety, the principal assessments will
      be shedding of the Ad4-H5-Vtn virus in rectal, cervicovaginal, throat, and nasal swabs, and
      assessment of the antibody (mucosal and systemic) response to the HA and to the Ad4 virus.
      Participants will remain in the NIH Special Clinical Studies Unit until they have 2
      consecutive negative nasal washes or 7 days have elapsed since vaccination, whichever occurs
      first; they may remain on the unit longer if medically necessary. When safety has been
      confirmed in all 3 participants at a given dosage level, the next higher dose group is
      enrolled. If one grade 3 or greater toxicity (or pre-specified grade 2 toxicity, see Section
      3.4) at least possibly related to the vaccine is observed, the group will be expanded at that
      dose. If a second at least possibly related grade 3 or greater toxicity (or pre-specified
      Grade 2 toxicity, see Section 3.4) is observed, the dose will be reduced one level and the
      group will be expanded. Up to 25 Ad4-seronegative individuals will be enrolled at the maximum
      tolerated dose to fully evaluate safety and immunogenicity in the protocol.

      All participants will be followed for 28 days following immunization, and again at 8 and 26
      weeks to evaluate any long-term toxicity and persistence of immunity. All subjects will be
      offered to receive a booster vaccine at the 26-week visit and be seen for follow-up visits 4
      and 8 weeks following booster immunization with an additional telephone follow-up 6 months
      after boosting. Household and intimate contacts will also be enrolled and monitored for
      Adenovirus and HAI antibodies following Ad4-H5-Vtn administration only; household and
      intimate contacts will not be enrolled or monitored during the boost portion of the study.

      We will conduct an expansion H5N1 boost phase of this study, in which all vaccinees from the
      initial phase of the study will be offered re-enrollment to receive a booster vaccination
      with an FDA-approved H5N1 inactivated monovalent influenza vaccine. We will offer enrollment
      in the expansion phase to all participants who received the Ad4-H5-Vtn vaccine in the initial
      phase, regardless of whether they also received the recombinant hemagglutinin influenza H5
      vaccine boost. We will also enroll individuals who have never received an H5 influenza
      vaccine as controls. Participants will receive a single vaccination with the H5N1 vaccine and
      be seen for follow-up visits 4 and 8 weeks later for immunogenicity evaluations.
    

Intervention name(s): Ad4-H5-Vtn
Intervention type(s): Biological
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Flu Vaccine; Healthy Volunteer