Flu Vaccine for Immune Response

(EVax-3 Trial)

Overseen By Jamie Mills

Age: 18 - 65

Sex: Any

Trial Phase: Phase 4

Sponsor: Washington University School of Medicine

Must not be taking: Immunosuppressants, Immune-modifying drugs

Disqualifiers: Pregnancy, Immunocompromised, Current smokers, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 6

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to compare immune responses in healthy adults after receiving one of two types of flu vaccines: the inactivated influenza vaccine (a standard shot) or FluMist (a nasal spray). Researchers seek to understand how these vaccines affect antibodies in the blood, nose, and lungs, particularly 14 days post-vaccination. Participants will be randomly assigned to receive one of the vaccines, with some opting for additional lung testing through bronchoscopy, a procedure to examine the lungs. Healthy individuals aged 18-40, who have not had a flu shot or flu in the past nine months, are suitable candidates for this study. As a Phase 4 trial, this study involves FDA-approved vaccines, aiming to understand how they benefit more patients.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on immunosuppressive drugs or have an unstable chronic disease requiring significant medical care, you may not be eligible to participate.

What is the safety track record for these treatments?

Previous studies have shown that FluMist is safe and effective. It uses a weakened virus that cannot cause the flu. Researchers have found that it helps the body build strong protection, similar to natural immunity. Most people tolerate it well, with few serious side effects reported.

The inactivated influenza vaccine is also very safe. It does not contain the live virus, so it cannot cause the flu. This vaccine has a great safety record. Most side effects are mild, such as a sore arm or a slight fever.

Both vaccines are FDA-approved, indicating thorough testing. These studies demonstrate they are safe for most people. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about these flu vaccines because they offer innovative approaches to boosting the immune response. Unlike traditional flu shots, FluMist is a nasal spray vaccine, making it easier and more comfortable to administer, especially for those who dislike needles. The inactivated influenza vaccine, on the other hand, is known for its stability and effectiveness, providing a reliable option for those with compromised immune systems. By comparing these two methods, researchers hope to uncover the best strategies for enhancing flu protection and potentially improving vaccination experiences for everyone.

What evidence suggests that this trial's treatments could be effective for immune response?

This trial will compare the effectiveness of the FluMist nasal spray and the inactivated flu shot in different groups. Studies have shown that both the FluMist nasal spray and the inactivated flu shot effectively prevent the flu. Research indicates that the inactivated flu shot can reduce the risk of flu by more than half in adults aged 18-65, with about 59% effectiveness. FluMist, a nasal spray vaccine, mimics a natural infection and has been found to protect children well. Both vaccines are similarly effective in preventing flu-like symptoms. Although neither vaccine is perfect, both significantly lower the chance of getting sick from the flu. ^{1 3 4 6 7}

Who Is on the Research Team?

Philip A. Mudd, M.D., Ph.D.

Principal Investigator

Washington University in Saint Louis School of Medicine

Are You a Good Fit for This Trial?

This trial is for healthy, non-pregnant adults aged 18-40 who want to help study the immune response to flu vaccines. Participants will receive either an inactivated influenza vaccine or FluMist intranasal vaccine and provide blood and nose swabs.

Inclusion Criteria

Able to understand and give written informed consent

In stable health, as determined by medical history and targeted physical exam related to the history

I am a healthy adult between 18 and 40 years old.

Exclusion Criteria

Pregnant women and nursing mothers or women who are planning to become pregnant during the study interval

Current smokers

Prisoners

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

Up to 6 weeks

1 visit (in-person)

Vaccination

Participants receive either the FDA-approved inactivated influenza vaccine or the FDA-approved intranasal FluMist vaccine

1 day

1 visit (in-person)

Immune Response Monitoring

Blood samples and nasopharyngeal swabs are collected to measure immune responses at various time points post-vaccination

3 months

Multiple visits (in-person)

Bronchoscopy Procedures (optional)

Optional bronchoscopy procedures for some participants to collect bronchoalveolar lavage and endobronchial biopsy samples

3 months

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 month

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• bronchoscopy
• FluMist
• inactivated influenza vaccine

Trial Overview The trial tests how the body's immune system responds to two FDA-approved flu vaccines: a shot (inactivated influenza vaccine) and a nasal spray (FluMist). It measures changes in specific antibodies in the lungs and nose up to 14 days post-vaccination.

How Is the Trial Designed?

Group I: FluMist no bronchoscopy group Experimental Treatment 1 Intervention

Individuals who do not complete day 14 or day 90 bronchoscopy procedures randomized to receive FluMist vaccine

Group II: FluMist bronchoscopy group Experimental Treatment 2 Interventions

Individuals who undergo all bronchoscopy procedures randomized to receive FluMist vaccine

Group III: inactivated influenza vaccine bronchoscopy group Active Control 2 Interventions

Individuals who undergo all bronchoscopy procedures randomized to receive inactivated influenza vaccine

Group IV: inactivated influenza vaccine no bronchoscopy group Active Control 1 Intervention

Individuals who do not complete day 14 or day 90 bronchoscopy procedures randomized to receive inactivated influenza vaccine

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

AstraZeneca

Industry Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5861782/

Immune responses after live attenuated influenza vaccination The immune responses elicted by LAIV mimic natural infection and have been found to provide broader clinical protection in children compared to the IIVs.

2. sciencedirect.com sciencedirect.com/science/article/pii/S0264410X25002439

Real-world effectiveness of influenza vaccination in ... Conclusions. An overall moderate, comparable effectiveness of LAIV-4 and IIV in preventing influenza/ILI among Italian children was observed.

3. cdc.gov cdc.gov/flu/vaccine-types/nasalspray.html

Live Attenuated Influenza Vaccine [LAIV] (The Nasal Spray ... Because of limited use, there have been no effectiveness estimates in the United States since LAIV was recommended again in the 2018-2019 ...

4. niaidcivics.org niaidcivics.org/news/2024/02/live-attenuated-and-inactivated-flu-vaccines-produce-differing-immune-responses/

Live Attenuated and Inactivated Flu Vaccines Produce ... Even when the vaccine matches currently circulating influenza strains, effectiveness has only reached about 60%. This limited effectiveness may indicate that ...

5. jamanetwork.com jamanetwork.com/journals/jama/fullarticle/302147

Effectiveness of Live, Attenuated Intranasal Influenza Virus ... Conclusion Intranasal trivalent LAIV vaccine was safe and effective in healthy, working adults in a year in which a drifted influenza A virus predominated.

6. flumisthcp.com flumisthcp.com/about-flumist/mechanism-of-action

Mechanism of Action | FluMist® (Influenza Vaccine Live ... FLUMIST induces a mucosal, cellular, and systemic immune response resembling natural immunity1,2* ...

7. mayoclinicproceedings.org mayoclinicproceedings.org/article/S0025-6196(11)61121-X/fulltext

Dispelling the Myths Associated With Live Attenuated ... Live attenuated influenza vaccine is a safe, highly immunogenic, and effective vaccine.