About this study

About this study

What is the purpose of the study?  

Influenza (‘flu’) is one of the most common causes of lung infection. Seasonal influenza affects between 10 and 46% of the population each year and causes around 12 deaths in every 100,000 people infected. There are three main types of flu virus: Influenza A, B and C. Influenza A causes most seasonal influenza cases and is the cause of flu pandemics. The virus can be found in many different animals and can spread between them, such as birds and wildfowl.  

Flu is transmitted by droplets, as well as aerosol and secretions from the mouth or nose of an infected person. It can also be spread by hand to mouth contamination from surfaces. Up to half of flu infections can show no symptoms, so it’s possible to spread it without knowing you’re infected. The incubation period can be 1-5 days (average 2-3 days).  

Common symptoms of flu include fever, chills, headache, muscle and joint pain and fatigue, as well as a cough, sore throat or stuffy nose. Most healthy people recover within 2-7 days. Complications are rare but more common in children under 6 months, older people, those with underlying health problems such as lung or heart disease or who are immunosuppressed, as well as pregnant women.  

The best way to protect against flu is through vaccination. Although influenza vaccines are available, these need to change every year to overcome rapid changes in the virus and are not completely protective.  We urgently need better vaccines that can: 

1. Protect against many different flu strains
2. Provide longer-lasting protection
3. Stop the spread of flu between people 

The flu vaccine routinely used in the UK for adults over the age of 18 is given by a jab into the arm. How well this vaccine protects against flu infection depends on several factors, such as the circulating strain of the flu virus, and how each individual responds to it. Because the vaccine given this way doesn’t completely protect against flu, there is a need to better understand how the body's immune system fights flu in the nose, throat, and lungs. As the flu virus gets into the body through the airways, focusing on the immune system in the airway can help design a better vaccine against flu.  

In this study, we'll compare the immune response when people get infected with flu versus when they receive a nasal spray flu vaccine. We will do this by taking blood, swabs and upper airway samples. This includes taking washes from the nose (nasal lavage), putting a soft paper strip in your nose, and a sample from the lining of the nose called a nasal scrape. In addition, in some participants we will take samples from the lower airway using a procedure called bronchoscopy. In another group of participants, we will take samples of their lymphoid tissue from the back of the nose. Lymphoid tissue - which is similar to the tonsils in the upper airway (nose and throat) has been shown to play an important role in the immune response to a flu vaccine given via the nose in children. This tissue is thought to play a role in helping create longer term and stronger immunity to flu. It is not yet known how important it is in adults. 

What does the study involve?  

This study involves a pre-screening visit where a member of the research team will discuss the study with you, ask you to sign a consent form and then collect a blood sample to look at your antibodies against influenza virus. This visit should take no longer than 1 hour and you will be paid £30 for attending this visit. We will also ask you if you have a preference for taking part in the vaccine or challenge arm of this study. 

If you meet the antibody threshold we are looking for, you will then be invited for a full screening visit which lasts approximately 3 hours. At the screening visit, the study doctor will discuss the study with you give you the opportunity to ask questions and then ask you to sign a consent form. During this visit, there will be a brief interview, medical examination, routine blood tests, urine tests, breathing tests and a chest X-ray to find out if you are suitable for the study. They will also request your medical history from your GP following the visit. You will be paid £75 for attending this visit. 

If you are eligible following screening, you will then be invited to take part in either the vaccine or challenge arm of the study.  

Influenza Vaccine Arm 

 The vaccine arm involves a baseline visit on Day -14 (14 days before) and Day -1 (one day before) the vaccination visit. On vaccination Day (Day 0), eligible participants will be given an influenza vaccine by nasal spray. 

 After the day of vaccination, they will be required to attend outpatient follow up visits on Day 1 (one day after), Day 3 (3 days after), Day 7 (7 days after) and Day 10. Participants in the vaccine arm will be paid up to £1,205 for time and inconvenience. 

Influenza Challenge Arm 

The challenge arm involves a baseline visit on Day -14 (14 days before) the residential stay. Eligible participants will be admitted to the residential facility on Day -1 (one day before) they are to be deliberately infected with the influenza virus. Participants will then remain in the residential facility until Day 8 if they remain uninfected, or until Day 10 if they become infected with influenza. Participants may experience some flu-like symptoms. Participants in the challenge arm will be paid up to £2,735 for time and inconvenience. 

All participants from both arms will undergo nasal biopsies OR bronchoscopies which will be explained in detail by the study team. They will then attend a follow up visit on Day 14, Day 28 and Day 180. After the Day 180 visit, your participation in the study will be complete.  

Who can take part? 

• You must be 18-40 years old (inclusive) at the time of enrolment 

• You must be willing and able to commit to the study procedures and visits 

• You must be in good health with no clinically significant medical conditions 

• You must NOT have a history of, or currently active, clinically significant illness. Examples include: 

• • Cancer 

• • Cardiovascular, thromboembolic or cerebrovascular diseases such as high blood pressure, stroke, heart failure and bleeding or clotting disorders  

• • Respiratory diseases such as asthma, COPD and cystic fibrosis 

• • Diabetes (Type 1 or 2) 

• • Any immunodeficiency or autoimmune disease  

• You must NOT have used inhalers or inhaled steroids in the last 12 months 

• You must NOT have had a cold or sinusitis in the past 6 weeks 

• You must NOT have received blood or blood products, or lost most than 550mL of blood in the last 3 months, including through blood donation 

• You must NOT have a significant history of using recreational drugs or excessive amounts of alcohol 

• You must NOT currently take drugs through the nose or by inhalation  

• You must NOT be a current regular smoker (including the use of e-cigarettes) 

• • If you are an ex-smoker, you must have quit more than 3 months ago and not smoked more than 5 pack years in your lifetime (use the Smoking Pack Years Calculator: https://www.smokingpackyears.com/ ) 

• You must NOT have severe allergies or intolerances, for example, to foods or medications, that cause severe allergic reactions such as anaphylaxis.  

• You must NOT be in close domestic contact (e.g. live with) anyone under 3 years old, or anyone over the age of 65 years or anyone who has a problem with their immune system or has a chronic lung condition.  

• You must NOT have taken part in another human viral challenge study in the last 6 months 

• You must have a Body Mass Index (BMI) between 18kg/m2 and 28kg/m2 

If you are a person of child-bearing potential:  

• You must NOT be currently pregnant 

• You must NOT be breastfeeding or have been breastfeeding within the last 6 months  
• You must NOT have been pregnant in the last 6 months 
• You must be willing to use effective contraception, such as the pill, an IUD (the coil), the implant or injection, or you must use condoms, until 6 months after enrolment. 

What is the duration of this study?  

Each participant will be in the study for approximately 6-7 months from screening to their last scheduled visit.   

Are there any potential benefits?  

Taking part will not improve anyone’s health, although they might develop some immunity to the study virus and benefit from a general health check at screening. Participants will be compensated for their time if they take part, up to £2,735.  

Ethics

The London Fulham Research Ethics Committee (REC) has reviewed and approved this study on 24th February 2025.

Review by an ethics committee is one of a series of safeguards intended to protect people taking part in all clinical research studies. It is a thorough process and there are many principles that are considered during the review, including weighing up the benefits against the risks. Another important consideration is making sure the potential participants receive high-quality, comprehensive information about the study in a timely fashion. The information about the study sent to and discussed with potential volunteers is very detailed and there are measures in place to make sure it is understood, so potential volunteers have a full picture of what the risks are and what the study entails before agreeing to take part (this is known as informed consent).

You can find out more about Research Ethics Committees (RECs) and the Health Research Authority (HRA) approvals on the HRA website: About us - Health Research Authority (hra.nhs.uk). A REC is made up of experts from different backgrounds (for example doctors, clinical trial experts, and scientists) and members of the public.