Human Challenge Trial of a Nucleoside-Modified Messenger Ribonucleic Acid Influenza Vaccine

Area of Science:

• Vaccinology
• Infectious Diseases
• Molecular Biology

Background:

• Human challenge trials are crucial for evaluating vaccine efficacy against influenza.
• Nucleoside-modified messenger RNA (modRNA) influenza vaccines represent a novel platform for influenza immunization.
• No prior human challenge trials have been reported for modRNA influenza vaccines.

Purpose of the Study:

• To assess the efficacy and safety of a modRNA influenza vaccine in a human challenge trial.
• To compare the modRNA vaccine's performance against a quadrivalent influenza vaccine (QIV) and a control group.
• To evaluate viral load reduction as a key efficacy endpoint.

Main Methods:

• A phase 2a, double-blind, randomized controlled trial was conducted.
• Healthy adults aged 18-55 received either a modRNA or QIV vaccine 30 days before influenza A/H1N1 challenge.
• Efficacy was measured by symptomatic and febrile influenza rates, viral load area under the curve (VL-AUC), and peak viral load (VL).

Main Results:

• The modRNA vaccine group showed 0% symptomatic influenza and 0% febrile influenza, achieving 100% vaccine efficacy (VE) for both endpoints.
• The quadrivalent influenza vaccine (QIV) group had 4.2% symptomatic and 0% febrile influenza, with VE of 84.5% and 100.0%, respectively.
• The modRNA vaccine demonstrated a significantly greater reduction in VL-AUC and peak VL compared to the control group, with no serious adverse events reported.

Conclusions:

• The modRNA influenza vaccine demonstrated superior efficacy compared to the control group in a human challenge model.
• The modRNA vaccine was well-tolerated, with no serious adverse events observed.
• These findings support the potential of modRNA technology for developing effective influenza vaccines.