Influenza Virus Challenge for Flu

Overseen by Matthew J Memoli, M.D.

Age: 18 - 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Waitlist Available

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

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial involves giving healthy adults a small dose of the H10N7 flu virus. Researchers will observe how their bodies respond to help develop better flu vaccines.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, it does exclude individuals with certain medical conditions and those who have received specific treatments recently, so it's best to discuss your medications with the trial team.

What data supports the effectiveness of the treatment A/Mallard/Ohio-99/MM4/1989 H10N7 for flu?

The research indicates that low pathogenic avian influenza viruses, like H10N7, can trigger a strong but short-lived immune response in mallards, suggesting that the virus may be controlled effectively by the immune system. Additionally, similar H10N7 viruses have been involved in outbreaks, indicating their ability to cause infection, which may imply potential for vaccine development. ^{1 2 3 4 5}

How is the drug A/Mallard/Ohio-99/MM4/1989 H10N7 different from other flu treatments?

The drug A/Mallard/Ohio-99/MM4/1989 H10N7 is unique because it involves a low pathogenicity avian influenza virus, which is not typically used in standard flu treatments. This approach may offer insights into how avian influenza viruses interact with hosts and could potentially inform the development of new strategies for managing flu infections. ^{2 3 6 7 8}

Research Team

Matthew J Memoli, M.D.

Principal Investigator

National Institute of Allergy and Infectious Diseases (NIAID)

Eligibility Criteria

Healthy adults aged 18-50 who can consent and agree to stay in isolation for at least 10 days without using tobacco, marijuana, or vaping. Women must meet specific fertility and HIV criteria; men must meet certain fertility conditions. Excludes those with significant medical issues, high-risk contacts, abnormal test results, recent illness or vaccinations, drug/alcohol abuse, psychiatric problems, non-English speakers.

Inclusion Criteria

Agrees to not use tobacco products, marijuana, or vaping products during participation

I am a woman following specific fertility and contraception guidelines and do not have HIV.

I am between 18 and 50 years old.

Exclusion Criteria

I have a serious long-term health condition like heart or lung disease.

I have a serious health condition like heart or lung disease, or I am immunocompromised.

I live with or am in close contact with high-risk individuals such as those over 65, under 5, or nursing home residents.

Treatment Details

Interventions

• A/Mallard/Ohio-99/MM4/1989 H10N7 (Virus Therapy)

Trial Overview The trial is testing the smallest dose of H10N7 flu virus that causes mild to moderate infection in healthy people. This will help evaluate new flu vaccines' effectiveness. Participants will receive one dose via nasal spray and be monitored closely with frequent tests and symptom surveys.

Participant Groups

Group I: 1 Experimental Treatment 1 Intervention

All participants receive challenge virus

Who Is Running the Clinical Trial?

National Institute of Allergy and Infectious Diseases (NIAID)

Lead Sponsor

Trials

3,361

Recruited

5,516,000+

Dr. Jeanne Marrazzo

National Institute of Allergy and Infectious Diseases (NIAID)

Chief Executive Officer since 2023

MD, MPH

Dr. H. Clifford Lane

National Institute of Allergy and Infectious Diseases (NIAID)

Chief Medical Officer

MD

Findings from Research

The low pathogenic avian influenza virus (LPAI) H1N1 triggers a strong but very short-lived innate immune response in mallards, with key immune genes RIG-I and Mx significantly upregulated just one day after infection but returning to normal levels by day two.

This rapid response suggests that the mallard's immune system has evolved to effectively control LPAI infections while minimizing potential damage from prolonged immune activation, highlighting the importance of the spleen in this process.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A rapid and transient innate immune response to avian influenza infection in mallards. Helin, AS., Wille, M., Atterby, C., et al.[2018]

The H10N7 avian influenza subtype caused outbreaks in Minnesota turkey farms in 1979 and 1980, with mortality rates reaching up to 31%, indicating a significant threat to poultry health.

The virus was found to be antigenically similar to strains isolated from healthy mallards nearby, suggesting that feral ducks may have introduced the virus to the turkey populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influenza A outbreaks in Minnesota turkeys due to subtype H10N7 and possible transmission by waterfowl. Karunakaran, D., Hinshaw, V., Poss, P., et al.[2007]

The highly pathogenic avian influenza A(H5N2) virus clade 2.3.4.4 was found in a wild mallard in Alaska in August 2016, indicating its reoccurrence in North America.

This discovery suggests that the virus can persist at low frequencies in migratory bird populations, raising concerns about its potential spread during migration seasons.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reoccurrence of Avian Influenza A(H5N2) Virus Clade 2.3.4.4 in Wild Birds, Alaska, USA, 2016. Lee, DH., Torchetti, MK., Killian, ML., et al.[2018]

In a study comparing two strains of avian influenza A viruses in mink, the H10N4 strain (A/mink/Sweden/3,900/84) caused more severe respiratory lesions and greater viral replication compared to the H10N7 strain (A/chicken/Germany/N/49).

Mink infected with the H10N4 strain showed significant inflammatory reactions, lower weight gain, and higher levels of the virus in their tissues, indicating that this strain is more pathogenic in mink than the H10N7 strain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two avian H10 influenza A virus strains with different pathogenicity for mink (Mustela vison). Englund, L., Hård af Segerstad, C.[2019]

References

1. England pubmed.ncbi.nlm.nih.gov

Low-pathogenicity influenza viruses replicate differently in laughing gulls and mallards. [2021]

2. England pubmed.ncbi.nlm.nih.gov

A rapid and transient innate immune response to avian influenza infection in mallards. [2018]

3. United States pubmed.ncbi.nlm.nih.gov

Influenza A outbreaks in Minnesota turkeys due to subtype H10N7 and possible transmission by waterfowl. [2007]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Development of Eurasian H7N7/PR8 high growth reassortant virus for clinical evaluation as an inactivated pandemic influenza vaccine. [2008]

5. Switzerland pubmed.ncbi.nlm.nih.gov

A Comparative Study of the Innate Humoral Immune Response to Avian Influenza Virus in Wild and Domestic Mallards. [2020]

6. United States pubmed.ncbi.nlm.nih.gov

Pathobiology and virus shedding of low-pathogenic avian influenza virus (A/H1N1) infection in mallards exposed to oseltamivir. [2013]

7. United States pubmed.ncbi.nlm.nih.gov

Reoccurrence of Avian Influenza A(H5N2) Virus Clade 2.3.4.4 in Wild Birds, Alaska, USA, 2016. [2018]

8. Austria pubmed.ncbi.nlm.nih.gov

Two avian H10 influenza A virus strains with different pathogenicity for mink (Mustela vison). [2019]