Immunogenicity and Safety of Live Attenuated Influenza Vaccine (Flumist) Administered by Nasal and Sublingual Route
Condition: Healthy
MeSH terms: Influenza, Human
Intervention: Influenza vaccine; Influenza vaccine
Intervention description: Administration of 1 dose (0.2 ml) by nasal route; Administration of 1 dose (0.2 ml) by sublingual route
Intervention MeSH terms: Vaccines
Phase: Phase 1
Study type: Interventional
Primary purpose: Basic Science
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 40.0
Sex: All
Minimum age: 20 Years
Maximum age: 49 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Influenza vaccine; nasal route; sublingual route; immunogenicity; safety

Summary:

      Background: It is well established that live attenuated organisms can be highly effective
      vaccines, immune responses elicited can often be of greater magnitude and of longer duration
      than those produced by non-living antigens and are often able to confer protection after a
      single dose. Unlike killed influenza vaccine preparations injected by the parenteral route,
      live influenza vaccines are able to induce potent secretory (mainly IgA) antibody responses
      in the airway mucosae and can also evoke cell mediated responses. T cell proliferation,
      cytokine production, cytotoxic T cell responses and antibody-dependent cell cytotoxicity have
      all been elicited by live attenuated vaccines.

      There has been a history of the use of live attenuated flu vaccines as safe and effective
      vaccines for the prevention of flu in animals and humans. Live-attenuated cold-adapted
      influenza vaccines have been proved to be highly efficacious to protect against clinical fly
      symptoms. Among these, FluMist, a nasal vaccine formulation developed by Medimmune Inc, has
      been approved by the US FDA. Recent side by side clinical trials have demonstrated that this
      nasal vaccine was significantly superior to conventional killed flu vaccine in protecting
      against flu symptoms.

      Sublingual administration of live influenza virus at a dose lethal by the nasal route was
      well tolerated and did not redirect virus to the olfactory bulb. In addition, in a recent
      Phase I clinical study (NCT00820144) conducted in France, the sublingual administration of
      recombinant cholera toxin B subunit (rCTB,up to 1 mg) in healthy adult volunteers was found
      to be safe.

      A major issue has arisen regarding the ease with which vaccines could be administered to
      young children, especially infants, and to elderly subjects in whom nasal vaccination has not
      been possible and/or approved due to difficulties of administering nasal vaccines in infants
      and to undesired side effects related to frequent rhinitis and sneezing episodes in elderly
      subjects. This study is designed to investigate the safety, tolerability and immunogenicity
      of a new route of administration of vaccines, using the nasal FluMist formulation as
      prototype vaccine.

      Objectives: To evaluate the immunogenicity and safety of a nasal and sublingual influenza
      virus vaccine (FluMist) in healthy adult volunteers

      Study design: This will be a randomized study on a total 40 subjects; each 20 subjects will
      receive vaccine via nasal and sublingual route, respectively
    

Eligibility criteria:

        Inclusion Criteria:

          -  Healthy volunteers who are able and willing to give informed consent, following a
             detailed explanation of participation in the study.

          -  Volunteers who will be available for the duration of the study and available for
             scheduled and potential additional visits

        Exclusion Criteria:

          -  Subjects with any clinically significant medical or psychiatric condition or
             clinically significant abnormal serum biochemistry or haematology results that, in
             opinion of the Investigator, preclude participation in the study.

          -  Female subjects who are pregnant (using urine test) or breast-feeding, or of
             childbearing potential and unwilling to use a reliable method of contraception (e.g.
             oral contraceptives or contraceptive during sexual activities such as a condom,
             contraceptive diaphragm, intrauterine device, hormonal contraceptive, or intercourse
             with a male partner who has had a vasectomy etc.) throughout the study period.

          -  Subjects who have known airway hypersensitivity to one of Flu vaccine excipients
             within 14 days prior to administration of study medication.

          -  Subjects who have known buccal hypersensitivity to any component of the vaccine or
             buffer solution used in this study, including subjects with phenylketonuria.

          -  Subjects with direct contact with at risk groups (e.g. patients in special care units,
             immuno-compromised individuals, pregnant women, children under 2 years of age and
             individuals over 70 years).

          -  Subjects with a known impairment of immune function including seropositive for HIV or
             those receiving (or have received in the 6 months prior to study entry) cytotoxic
             drugs immunosuppressive therapy (including systemic corticosteroids).

          -  Subjects with a significant acute febrile illness (fever of 38.0 Celsius degree or
             more) at time of dosing.

          -  Subjects who have chronic diseases: Chronic diseases will include all autoimmune and
             immuno-compromising conditions and any other chronic condition, which at the judgement
             of the Investigator, may put the subject at higher risk of side effects from the study
             vaccine. Conditions in the latter category might include unexplained anaemia,
             hepato-biliary disease, uncontrolled hypertension, subjects with prosthetic joints or
             heart valves, etc.

          -  Subjects with a current problem, based on history, with substance abuse or with a
             history of substance abuse

          -  Subjects who are currently involved in a clinical trial, have taken an investigational
             drug or have received investigational or licensed vaccines in the preceding 4 weeks or
             anticipate receiving a vaccine other than study medication during the first 4 weeks of
             the study

          -  Subjects who have known hypersensitivity to eggs or egg proteins

          -  Subjects who have chronic respiratory infections or syndromes

          -  Unable to receive oral (sublingual) administration.

          -  Receiving anti-viral agents.

          -  Subjected to contraindications and/or precautions described in drug information