Mucosal and Systemic Immunity After Viral Challenge of Healthy Volunteers Vaccinated With Inactivated Influenza Vaccine Via the Intranasal Versus Intramuscular Route
Condition: Influenza
MeSH terms: Influenza, Human
Study type: Interventional
Phase: Phase 2

Summary: 
      Background:

      Influenza (flu) is a contagious respiratory virus that makes humans sick. Usually its
      symptoms are mild, but they can be dangerous. Researchers want to see if one way of giving
      the flu vaccine is more effective than another.

      Objective:

      To compare the body s ability to fight infection when a flu vaccine is given in the nose
      versus the arm.

      Eligibility:

      Healthy, nonsmoking adults ages 18 55. They must be willing to stay in isolation for at least
      9 days. They must not have had the flu vaccine since September 1, 2018.

      Design:

      Participants must be willing to use birth control or abstinence from visit 1 until 8 weeks
      after getting the flu virus.

      Participants will have at least 3 clinic visits over about a month. Visits may include:

      Medical history

      Physical exam

      Blood and urine tests

      Nasal samples collected

      Heart and lung function tests

      At the first visit, participants will get either:

      Flu vaccine as injection in an arm muscle plus salt water sprays in the nose

      OR flu vaccine as sprays in the nose plus salt water injection in an arm

      Within the next few months, participants will stay in an isolation room for at least 9 days.
      They will be with up to 20 participants. Those who test positive for recreational drugs will
      leave the study. Participants will:

      Repeat study tests

      Answer questions about flu symptoms

      Have the flu virus sprayed into their nose once

      Be monitored by a medical team

      Participants will have at least 2 follow-up visits and repeat study tests.
    

Detailed description: 
      The high morbidity and mortality associated with both pandemic and seasonal influenza and the
      threat of new potentially pandemic strains emerging makes influenza an important infectious
      disease and public health problem. Public health agencies must continue attempts to reduce
      the public health impact of this important virus.

      Currently, influenza vaccination is the cornerstone of prophylaxis and the most effective
      method available to reduce the impact of influenza on the population. Current vaccines target
      the major surface protein, hemagglutinin (HA), and are standardized by stimulation of serum
      anti-HA antibodies as the primary correlate of protection. Measurements of serum antibodies
      to HA have become the gold standard for evaluating vaccines. The Food and Drug Administration
      (FDA) and the European Medicines Agency (EMA) Committee for Medicinal Products for Human Use
      (CHMP) both define protective titers as a hemagglutination inhibition (HAI) titer of greater
      than or equal to 40. Recent vaccine effectiveness has been limited and, in some populations,
      estimated at as low as 10%. Improved methods of vaccination must be developed, but limited
      information regarding the true correlates of protection is available. Correlates of
      protection in the systemic circulation may be less informative than those located in the
      nasopharyngeal mucosa, which is the site of exposure to and infection with influenza virus.

      This study is designed to characterize the mucosal and systemic immunologic correlates of
      protection from influenza infection in persons vaccinated and unvaccinated against influenza.
      Half of participants will receive current licensed quadrivalent inactivated influenza vaccine
      (IIV) administered via the intramuscular (IM) route at the standard dose, prior to challenge
      with influenza virus. The other half will receive no vaccination prior to challenge.
      Immunologic response and clinical outcomes in the human challenge model will be determined to
      characterize the two cohorts. In the vaccinated cohort, mucosal and systemic immune responses
      induced by IM administration of quadrivalent IIV will also be carefully explored. The
      thoughtful study of mucosal immunity to influenza is expected to identify novel correlates of
      protection. By administering quadrivalent IIV and then infecting participants with human
      challenge virus, we can evaluate in detail the immunologic responses after immunization and
      subsequent virus exposure. This controlled setting offers the ideal environment to query
      these responses and to identify targets of mucosal stimulation for future vaccine strategies.
      In addition, the detailed characterization of the mucosal and systemic immune responses after
      vaccination and challenge will represent a true advance in understanding influenza immunity.
    

Intervention name(s): Flucelvax(R); Human Challenge virus
Intervention type(s): Biological; Other
Intervention description(s): Cohort 1 will receive IM quadrivalent IIV (Flucelvax (R)) at the standard dose of 15 micrograms HA per strain (60 micrograms HA total).; A dose of 10^7 50% tissue culture infective dose (TCID50) of human challenge virus will be administered intranasally to all participants using a nasal sprayer.
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: Human Challenge; Vaccine; Immune Response; Challenge Study; Healthy Volunteer