Evaluation of Anti-Hemagglutinin (Anti-HA) Antibodies as Protection From the Flu in Healthy People

Phase 1

Completed

Conditions: Influenza

Interventions: Biological: Ca/04/2009/H1N1r Challenge Virus

Registration Number: NCT01971255

Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Brief 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 74

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
High Titer (HAI > or = 1:40)	Ca/04/2009/H1N1r Challenge Virus	Subjects with prechallenge hemagglutination inhibition (HAI) titers of ≥1:40 were assigned to this group. The human challenge virus, Ca/04/2009/H1N1r 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.
Low Titer (HAI < 1:40)	Ca/04/2009/H1N1r Challenge Virus	Subjects with prechallenge hemagglutination inhibition (HAI) titers of \<1:40 were assigned to this group. The human challenge virus, Ca/04/2009/H1N1r 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.

Primary Outcome Measures

Name	Time	Method
Number of Patients With Mild to Moderate Influenza Disease (MMID)	Within 10 days of inoculation	This was determined by presence of the combination of symptoms of influenza and presence of a positive clinical test for influenza. If both were present then the participant had positive MMID.

Secondary Outcome Measures

Name	Time	Method
Clinical Disease Severity Score	Within 28 days after inoculation	This was measured using a validated participant directed questionnaire called FLUPRO. This is then scored daily with a range of score from 0-185. The total score is the sum of all time points the questionnaire is given, which is 16 time points. Therefore the total score range is from 0-2960. 0 would represent no symptoms over the 16 time points while 2960 would represent maximum symptoms and perceived severity at all 16 time points.
Duration of Shedding (Days)	Within 14 days of inoculation	The number of days total from the time a participant had the first positive test for influenza to their last positive test.
Duration of Symptoms (Days)	within 68 days after inoculation	The number of days a participant experienced any influenza symptoms
Number of Symptoms	within 68 days after inoculation	A simple count of the number of unique influenza symptoms the participant experienced.
Number of Participants With Influenza Symptoms	within 68 days after inoculation	This was determined by the presence or absence of influenza symptoms.