A clinical trial in which healthy adults will be deliberately infected with influenza virus under carefully controlled conditions has begun recruiting volunteers at four Vaccine and Treatment Evaluation Units (VTEUs) supported by the National Institute of Allergy and Infectious Diseases (NIAID). The first five volunteers received doses of the challenge virus earlier this week, marking the start of this innovative research approach.
The primary objective of the study is to evaluate how pre-existing influenza antibodies impact the timing, magnitude, and duration of flu symptoms following exposure to the influenza virus. This controlled human infection model provides researchers with a unique opportunity to study influenza disease progression in real-time and evaluate immune responses.
"NIAID investigators have been pioneers in contemporary human influenza challenge trials," said NIAID Director Anthony S. Fauci, M.D. "These trials provide a powerful tool to study many aspects of influenza disease progression and also can help to efficiently assess new treatments and vaccine candidates."
Study Design and Protocol
The trial will enroll up to 80 healthy adults aged 18 to 50 years across four VTEU sites. Participants will receive a nasal spray containing the InfluenzaA/Bethesda/MM2/H1N1 strain, which was developed by NIAID scientists specifically for challenge studies. This strain has been shown to produce mild to moderate influenza symptoms in most recipients and has been safely administered to approximately 400 participants in four previous challenge trials at the NIH Clinical Center in Bethesda, Maryland.
Following administration of the virus, volunteers will remain in the clinic for a minimum of seven full days under careful medical supervision. Researchers will collect blood samples and nasal and throat swabs before and periodically after viral challenge to track immune system responses and detect virus shedding. Participants will record flu symptoms daily for 14 days, and follow-up monitoring will continue for approximately 90 days post-challenge.
Dr. Fauci emphasized the strategic importance of this research: "Expanding the capacity to perform human challenge trials is a key goal in NIAID's strategic plan to support the development of vaccines that confer broad and durable protection against influenza. This new trial at the VTEUs will help us achieve that goal."
Research Sites and Leadership
The study is being conducted at four NIAID-supported Vaccine and Treatment Evaluation Units across the United States:
- University of Maryland School of Medicine, Baltimore (lead site) – Principal Investigator: Dr. Kathleen Neuzil
- Cincinnati Children's Hospital Medical Center – Principal Investigator: Dr. David Bernstein
- Duke University, Durham, North Carolina – Principal Investigator: Dr. Christopher Woods
- Saint Louis University Center for Vaccine Development – Principal Investigator: Dr. Daniel Hoft
Safety Considerations
The challenge virus has demonstrated a strong safety profile in previous trials. No significant safety issues, severe cases of influenza, or transmission of the virus outside of clinical settings have been observed in earlier studies. The current protocol includes comprehensive safety monitoring and medical supervision throughout the in-patient stay and follow-up period.
Significance for Vaccine Development
Human challenge studies represent a powerful approach to accelerate vaccine development by allowing researchers to study disease mechanisms and immune responses in a controlled environment. This methodology can significantly reduce the time and resources needed to evaluate new vaccine candidates compared to traditional field trials.
The insights gained from this study could prove crucial for developing next-generation influenza vaccines that provide broader and more durable protection against multiple influenza strains – a major public health priority given the seasonal burden of influenza and the ongoing threat of pandemic potential.
Preliminary results from this challenge study are expected in May 2020. The trial is registered on ClinicalTrials.gov under the identifier NCT04044352.
For those interested in participating in this research, the trial requires a minimum 10-day in-patient stay as well as in-person pre- and post-challenge visits to the clinic. Potential volunteers can inquire about enrollment through a form available on the NIAID website.
