Evaluation of Anti-Hemagglutinin (Anti-HA) Antibodies as Protection From the Flu in Healthy People
Condition: Influenza
MeSH terms: Influenza, Human
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      Background:

      - Researchers want to know if a certain type of antibody in the blood affects whether people
      get influenza (the flu). They will study 2 different groups with different levels of anti-HA
      antibodies and expose them to the flu virus. They will study how the flu develops in a
      healthy person. This may lead to future studies to develop new vaccines and treatments for
      the flu.

      Objective:

      - To study how people can be protected from flu infection.

      Eligibility:

      - Healthy volunteers 18 to 50 years of age.

      Design:

        -  Participants will be screened through the use of a medical history, physical exam, and
           laboratory tests.

        -  Groups of 7 participants will stay in an isolation unit in a hospital for at least 9
           days with no visitors.

        -  Participants will be screened again upon admission. They will also have:

        -  ECG: soft electrodes will be stuck to the skin. A machine will record the heart s
           electrical signals.

        -  Echocardiogram: a small probe will be held to the chest to take pictures of the heart.

        -  Lung tests: participants will blow into a machine.

        -  They will also have nasal fluid collected. This will be done either with a swab or with
           a tube of water washing out the nose. This will be done once every day.

        -  The flu virus will be sprayed into the participant s nose. This will be done only once.

        -  Participants will complete a questionnaire on day 1 and twice a day after that for 14
           days.

        -  A medical team will watch participants 24 hours a day. They will go home after 2 days of
           negative flu tests.

        -  Participants will have 4 follow-up visits over 8 weeks.
    

Detailed description: 
      The high morbidity and mortality associated with both pandemic and seasonal influenza, and
      the threat of new pandemic strains emerging, continues to keep influenza at the forefront of
      infectious disease and public health research. Mean annual estimates of influenza deaths due
      to seasonal influenza alone, attributes 36,000 deaths in the US and 250,000 to 500,000 deaths
      in industrialized countries to influenza. Pandemics can have an even more devastating effect,
      and we must continue to be prepared by making attempts to reduce the public health impact of
      this important virus.

      Currently, influenza vaccination is the cornerstone of prophylaxis and most effective method
      available to reduce the impact of influenza on the world s population each year. Data from
      the 2013 influenza season suggest that current seasonal vaccines held to these standards are
      greatly underperforming especially in those that really need protection such as the elderly,
      young, and infirmed.

      Multiple factors could play a role in defining the true correlates of protection to influenza
      infection and disease and many of these factors are yet to be clearly defined. In our own
      influenza challenge study, protocol 12-I-0077, we have clearly seen evidence that not
      everyone with a low HAI titer is susceptible to influenza, and that there must be other
      factors protecting certain individuals. There are many examples like this that demonstrate
      that there may be much more to immune protection to influenza than just anti-HA antibodies.

      Live virus challenge studies have played an important role in defining the correlates of
      protection of influenza in the past, and we believe they can continue to do so in the future.
      Since the last time a wild-type influenza challenge has been performed to investigate
      correlates of protection over 20 years ago, many new scientific tools and a significant
      increase in knowledge of the immune system have developed. In this study we will enroll
      participants at different hemagglutinin inhibition titer levels and evaluate this as a
      correlate of protection to the 2009 H1N1 while exploring the other possible correlates of
      protection that may be identified. This study represents the first opportunity to examine the
      correlates of protection of influenza in a fully validated and described wild-type virus
      challenge model. We believe that studies like this are an ideal use of a wild-type influenza
      challenge study and can lead to intelligent universal vaccine design as well as a basis to
      begin evaluating novel vaccine strategies in wild-type challenge studies in the future.
    

Intervention name(s): Ca/04/2009/H1N1r Challenge Virus
Intervention type(s): Biological
Intervention description(s): The human challenge virus will be administered intranasally to each participant using a nasal sprayer. A total volume of up to 1 mL of virus will be administered.
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: Influenza A; HAI; H1N1; Challenge Study; Correlates of Protection