Influenza A H3N2 Human Challenge Study in Healthy Adult Volunteers
Condition: Determine Minimally to Moderately Infective Dose (MMID) of Influenza A H3N2
MeSH terms: Influenza, Human
Study type: Interventional
Phase: Phase 1

Summary: 
      Background:

      Influenza A H3N2 is a flu virus. Symptoms include fever, cough, and runny nose. It can also
      be more serious. Researchers want to know more about how influenza causes disease in people.
      They hope to develop new vaccines and treatments for flu infection.

      Objective:

      To find the smallest amount of Influenza A H3N2 virus that causes a mild to moderate flu
      infection in healthy people. Also, to study the body s immune response to this virus and how
      the infection develops.

      Eligibility:

      Healthy people ages 18 50 who are:

      Non-smokers or non-habitual smokers

      Willing to not smoke for at least 9 days

      Design:

      Participants will be screened under NIAID protocol #11-I-0183

      Participants will stay at an isolation unit at the clinic for at least 9 days. They will
      remain in the isolation unit except for study-specific activities.

      The influenza virus will be sprayed into the nose.

      Participants will be monitored 24 hours a day. They will have tests, including:

      Medical history

      Physical exam

      Daily questionnaires about symptoms

      Blood and urine tests

      Nasal wash and swab: A small tube of salt water is placed in the nose to wash it. It then
      collects the

      fluid. Or the inside of the nose is rubbed with a swab.

      ECG: Measures the heart s electrical signals

      ECHO: Sound waves take pictures of the heart

      PFTs/Spirometry: They will blow into a machine that measures the air they blow.

      Participants will be discharged after they test negative for influenza A.

      Participants will return to the clinic for 4 follow-up visits over 8 weeks. They may complete
      questionnaires at home.
    

Detailed description: 
      The high morbidity and mortality associated with both pandemic and seasonal influenza, and
      the anticipation of future influenza pandemics, puts influenza front and center in infectious
      disease research. Because the natural history and pathogenesis of human influenza has not
      been well characterized and cannot be adequately studied in animal models or with current in
      vitro techniques, important questions about influenza pathogenesis can only be approached
      through human challenge studies.

      Although studies of influenza in healthy volunteers have played an important role in
      addressing aspects of the natural history of influenza disease and developing novel
      antivirals, prior to recently these important studies had not been performed in the US in
      over a decade. The H1N1 challenge studies we have performed since 2012 have sought to improve
      upon the studies done in the past and address many of the limitations due to the scope of the
      studies and/or the scientific techniques available at that time. We have successfully
      developed an H1N1 model that had been used to address important questions regarding
      correlates of protection and is now being implemented to develop new drugs and vaccines. We
      hope to develop H3N2 models that can be just as useful.

      The primary objective of this study is to determine the dose of influenza A H3N2 human
      challenge virus that will induce a mild to moderate uncomplicated influenza infection in
      healthy volunteers. This protocol will examine some of the basic questions that remain
      unanswered regarding the pathogenesis of H3N2 influenza in humans, namely, a detailed
      clinical and immunological characterization of uncomplicated influenza viral pathogenesis in
      healthy adult volunteers.

      Secondary objectives will evaluate clinical disease, length of viral shedding, and
      pathogenesis in those with influenza infection including identification of clinical markers
      of the disease. Notably, the exploratory objectives will seek to discover viral factors
      necessary for human infection/adaptation and to evaluate host immune response, viral
      replication, viral fitness, and the intrahost evolution.

      Collaboration between NIAID investigators and outside scientists will generate opportunities
      to further develop and expand areas of clinical influenza research based on the proposed H3N2
      challenge model.
    

Intervention name(s): Live recombinantly derived A/Bethesda/MM1/H3N2 virus
Intervention type(s): Other
Intervention description(s): The human challenge virus will be administered intranasally to each participant using a nasal sprayer. A total volume of up to 2mL of virus will be administered.
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: Influenza A; H3N2; Challenge Model; Influenza; Human Challenge