Influenza Virus for Influenza

Recruiting at1 trial location

Overseen by Nadine Rouphael, MD

Age: 18 - 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Emory University

Must not be taking: Antivirals, NSAIDs, Steroids, Antihistamines

Disqualifiers: Pregnancy, Cardiovascular disease, Immunosuppression, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This study is designed to help us better understand how the immune system responds to the flu and how flu is transmitted in the environment. The ultimate goal is to develop better vaccines and drugs to protect against or fight the flu. This study will describe how the body's immune system responds to the flu virus during and after infection and how the flu virus is transmitted in the environment. The study will use a flu virus called A/Texas/71/2017 (H3N2), clade 3C3a produced specifically for clinical research in controlled conditions. The study will also assess the safety of the H3N2 influenza challenge in healthy participants. Mild to moderate symptoms are expected based on previous studies with this strain of influenza. Study volunteers will be recruited and screened from the general population of metro Atlanta through advertisements or identified from a database of research participants who have previously agreed to be contacted for future research studies. Participants will provide written consent before study participation. Up to 200 healthy adults, 18-49 years old, will be screened for participation. Eligible participants will take part in the study over 5 months. Enrolled participants will be admitted to Emory University Hospital during which time they will receive the influenza virus in the form of a spray in the nose or exposure to infected participants followed by an 8-12 day inpatient stay for observation. Follow-up outpatient visits will take place at the Hope Clinic of the Emory Vaccine Center. Participants will receive compensation (pro-rated for all visits completed) for their time and effort. There will be no costs to participants as a result of being in the study.

Will I have to stop taking my current medications?

Yes, you will need to stop taking certain medications that could affect the study, such as flu medications, aspirin, intranasal steroids, and some pain relievers, at least 14 days before the study and during the quarantine period, unless approved by the study investigator.

What data supports the effectiveness of the treatment Influenza A H3N2 strain for influenza?

The effectiveness of the Influenza A H3N2 strain in vaccines can vary due to the virus's rapid evolution, which sometimes leads to a mismatch between the vaccine strain and the circulating virus. For example, during the 2016/2017 flu season, the H3N2 component of the vaccine had a low protective efficacy of about 28-42% against infection. ^{1 2 3 4 5}

How is the Influenza A H3N2 strain treatment different from other treatments for influenza?

The Influenza A H3N2 strain treatment is unique because it targets a specific subtype of the influenza virus that has rapidly evolved and is associated with severe flu seasons. Unlike standard vaccines, which may have lower effectiveness against this strain, this treatment focuses on the H3N2 subtype's unique genetic and antigenic changes, potentially offering more targeted protection. ^{4 6 7 8 9}

Research Team

Nadine Rouphael, MD

Principal Investigator

Emory University

Eligibility Criteria

Healthy adults aged 18-49 in the metro Atlanta area can join this flu study. They must be willing to stay at Emory University Hospital for up to 12 days and attend follow-up visits. People with weak immune systems or certain medical conditions cannot participate.

Inclusion Criteria

Persons of childbearing potential must have a negative serum or urine pregnancy test at screening and a negative urine pregnancy test within 24 hours before challenge

Can understand and comply with all planned study procedures

Persons biologically able to become pregnant must be practicing abstinence or using an acceptable method of birth control for at least 30 days before the challenge through the duration of the trial

Exclusion Criteria

Have screening laboratory test results that are outside the laboratory reported normal values and deemed clinically significant by the study investigator

I have an active HIV, hepatitis B, or hepatitis C infection.

Have a pulse rate of less than 55 bpm or greater than 100 bpm

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

8 weeks

1 visit (in-person)

Challenge and Observation

Participants receive the influenza virus via nasal spray or exposure to infected participants, followed by an 8-12 day inpatient stay for observation

2 weeks

Inpatient stay

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Outpatient visits at the Hope Clinic

Treatment Details

Interventions

• Influenza A H3N2 strain (Virus Therapy)

Trial Overview The trial is testing how a specific flu virus (A/Texas/71/2017 H3N2) affects the body and spreads. Participants will get the virus through a nasal spray or by being near infected people, while their immune response and transmission are studied.

Participant Groups

Group I: Live Influenza Virus RG-A/Texas/71/2017 (H3N2 Experimental Treatment 1 Intervention

Participants will be pre-screened up to sixty days before the challenge study to identify baseline HAI titer. Participants will either be in the intranasal challenge or the natural exposure cohort.

Who Is Running the Clinical Trial?

Emory University

Lead Sponsor

Trials

1,735

Recruited

2,605,000+

Dr. R. Donald Harvey

Emory University

Chief Medical Officer

MD from Emory University School of Medicine

Dr. George Painter

Emory University

Chief Executive Officer since 2013

PhD in Synthetic Organic Chemistry from Emory University

NATIONAL PHILANTHROPIC TRUST

Collaborator

Trials

1

Recruited

50+

Findings from Research

The 2002/2003 influenza season saw a moderate epidemic primarily caused by Influenza A (H3N2) and B viruses, with H3N2 dominating hospital isolates, indicating a need for effective monitoring and vaccination strategies.

A variant of H3N2, A/Fujian/411/02, was identified as a potential concern due to its poor reaction with the vaccine strain, suggesting a risk of vaccine mismatch for the upcoming season.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The 2002/2003 influenza season in the Netherlands and the vaccine composition for the 2003/2004 season]. de Jong, JC., Rimmelzwaan, GF., Bartelds, AI., et al.[2014]

A study of 33 patients over three influenza seasons (2009-2011) in Quebec revealed significant antigenic drift in A/H3N2 viruses, indicating that the vaccine strains used were not well matched to circulating viruses, which can reduce vaccine effectiveness.

The research highlighted that while multiple mutations occurred in the HA gene, only a few strains showed significant antigenic drift, suggesting that both the number and specific locations of mutations are crucial in determining how the virus evolves and affects vaccine efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular and antigenic evolution of human influenza A/H3N2 viruses in Quebec, Canada, 2009-2011. Ann, J., Papenburg, J., Bouhy, X., et al.[2011]

The study evaluated the effectiveness of various A/H3N2 vaccine strains over the past decade, finding that certain strains (PE/09, VI/11, TE/12) induced higher levels of neutralizing antibodies compared to others (HK/14, HK/19, CA/20), highlighting the importance of selecting effective vaccine strains.

Immunizing guinea pigs with three doses of monovalent vaccine stock resulted in stronger and broader neutralizing antibody responses against diverse circulating strains, suggesting that increasing the frequency of immunization could enhance protection against influenza A (H3N2).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retrospective immunogenicity analysis of seasonal flu H3N2 vaccines recommended in the past ten years using immunized animal sera. Zhang, M., An, Y., Wu, X., et al.[2022]

The H3N2 subtype of influenza A has been linked to severe flu seasons, with a notably low vaccine efficacy of only 28-42% during the 2016/2017 season against circulating strains.

H3N2 viruses have rapidly evolved since their introduction in 1968, developing genetic and antigenic changes that complicate vaccine effectiveness and virus characterization, including modifications to their hemagglutinin and neuraminidase proteins.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

H3N2 influenza viruses in humans: Viral mechanisms, evolution, and evaluation. Allen, JD., Ross, TM.[2019]

A multidrug-resistant H3N2 influenza virus developed in an immunocompromised patient after just 5 days of oseltamivir treatment, showing a significant increase in resistance to this antiviral medication.

The virus exhibited a specific genetic change (a 4-amino acid deletion in the neuraminidase gene) that reduced sensitivity to oseltamivir and zanamivir, but it did not affect the virus's fitness or ability to spread, highlighting the challenges of treating influenza in vulnerable populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rapid selection of a transmissible multidrug-resistant influenza A/H3N2 virus in an immunocompromised host. Memoli, MJ., Hrabal, RJ., Hassantoufighi, A., et al.[2021]

The study estimated that there were approximately 2055 illnesses caused by the H3N2v virus in the U.S. from August 2011 to April 2012, indicating that the virus was more widespread than laboratory-confirmed cases suggested.

Using a multiplier model, the researchers found that the true burden of illness was significantly underestimated, with multipliers of 200 for children and 255 for adults, highlighting the need for improved surveillance and detection of H3N2v infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Estimates of the number of human infections with influenza A(H3N2) variant virus, United States, August 2011-April 2012. Biggerstaff, M., Reed, C., Epperson, S., et al.[2021]

A new H3N2 influenza virus strain was identified in Germany from pigs showing flu symptoms, characterized by various tests and complete genome sequencing.

This strain is a reassortant, combining genes from both prevalent European porcine H3N2 and H1N2 viruses, indicating ongoing evolution and reassortment among swine influenza viruses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ongoing evolution of swine influenza viruses: a novel reassortant. Zell, R., Bergmann, S., Krumbholz, A., et al.[2008]

Swine in Hong Kong carry H3N2 influenza A strains that are closely related to historical human strains, indicating that they may serve as a reservoir for both old and new variants of the virus.

The study used reciprocal hemagglutination inhibition tests and neuraminidase inhibition tests to confirm the relationships between swine and human strains, highlighting the potential for swine to contribute to influenza virus evolution and transmission to humans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Further studies of the antigenic properties of H3N2 strains of influenza A isolated from swine in South East Asia. Shortridge, KF., Cherry, A., Kendal, AP.[2006]

The study identified two antigenically distinct groups of the H3N2 influenza virus, SW13 and HK14, that co-circulated during the 2014-2015 winter season, which is crucial for understanding the virus's evolution and its impact on public health.

Key mutations near the receptor-binding site on the hemagglutinin protein were found to significantly influence the antigenic variation of these H3N2 strains, providing valuable insights for future vaccine strain selection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antigenic variation of the human influenza A (H3N2) virus during the 2014-2015 winter season. Hua, S., Li, X., Liu, M., et al.[2015]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

[The 2002/2003 influenza season in the Netherlands and the vaccine composition for the 2003/2004 season]. [2014]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Molecular and antigenic evolution of human influenza A/H3N2 viruses in Quebec, Canada, 2009-2011. [2011]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Retrospective immunogenicity analysis of seasonal flu H3N2 vaccines recommended in the past ten years using immunized animal sera. [2022]

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

H3N2 influenza viruses in humans: Viral mechanisms, evolution, and evaluation. [2019]

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

Rapid selection of a transmissible multidrug-resistant influenza A/H3N2 virus in an immunocompromised host. [2021]

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

Estimates of the number of human infections with influenza A(H3N2) variant virus, United States, August 2011-April 2012. [2021]

7. Austria pubmed.ncbi.nlm.nih.gov

Ongoing evolution of swine influenza viruses: a novel reassortant. [2008]

8. England pubmed.ncbi.nlm.nih.gov

Further studies of the antigenic properties of H3N2 strains of influenza A isolated from swine in South East Asia. [2006]

9. China pubmed.ncbi.nlm.nih.gov

Antigenic variation of the human influenza A (H3N2) virus during the 2014-2015 winter season. [2015]