NCT07240922

The Dynamics of the Immune Responses to Repeat Influenza Vaccination Exposures (DRIVE III) Study

The Dynamics of the Immune Responses to Repeat Influenza Vaccination Exposures (DRIVE III) Study - a Randomized Controlled Trial

• Status: Recruiting
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 600 (estimated)
• Sponsor: The University of Hong Kong · Academic / Other
• Sex: All
• Age: 22 Years – 50 Years
• Healthy volunteers: Accepted

Summary

This study will provide novel insight into the effects of repeat influenza vaccination with Flublok and FluMist on the strength and breadth of immune responses to influenza, the mechanisms underlying heterogeneity in vaccine response and vaccine failure, and biological factors that could explain variation in influenza vaccine effectiveness.

Detailed description

Annual vaccination remains a key public health approach to reducing the impact of influenza virus infections. However, numerous trials and observational studies, including our own, have demonstrated that repeated an-nual influenza vaccination can result in attenuated vaccine effectiveness in some years in a phenomenon called "repeat vaccination effects". Gaining insight into the varying efficacy of influenza vaccines across different individuals and populations is crucial for optimizing the use of current vaccines and designing universal ones. However, understanding the changes in vaccine effectiveness and immunogenicity among those receiving repeated vaccinations is challenging, especially in populations where universal vaccination is recommended. Repeated vaccinees differ significantly from both new vaccinees and non-vaccinees, potentially leading to residual con-founding in infection and vaccination histories, making it hard to isolate the effects of the vaccine itself. The investigators will conduct a randomized trial to explore the effects of repeated vaccination and their immunological foundations in a population with low vaccine coverage and no influenza vaccination recommendation. The study will involve live attenuated influenza vaccines (FluMist, nasal spray) in addition to parenteral influenza vaccines (Flublok, injected) to stimulate different components of the immune system. The trial will involve 600 adults in Hong Kong, divided into four groups. The four groups will receive annual vaccination with Flublok, FluMist, alternating between these two vaccines, or alternating between Flublok and placebo. This structure enables comparisons of humoral, mucosal and cellular vaccine responses after different combinations of vaccines. The resulting longitudinal data on immune status and influenza-specific responses will allow the investigators to develop predictive models for vaccine and infection responses, including those involving repeat vaccinations. The planned immunological profiling, alongside advanced statistical analysis, will enhance understanding of repeated vaccination's effects on seasonal influenza and inform strategies to anticipate vaccine non-responsiveness and improve vaccination approaches. Stored specimens will also allow future testing of new hypotheses.

Conditions

• Influenza

Interventions

Type	Name	Description
BIOLOGICAL	Live attenuated influenza vaccine	0.2mL nasal spray live attenuated influenza vaccine (FluMist, AstraZeneca)
BIOLOGICAL	Placebo nasal spray	0.2mL saline placebo nasal spray
BIOLOGICAL	recombinant hemagglutinin influenza vaccine	0.5mL recombinant hemagglutinin influenza vaccine (Flublok, Sanofi)
BIOLOGICAL	Placebo injection	0.5mL saline placebo injection

Timeline

• Start date: 2025-10-01
• Primary completion: 2030-10-01
• Completion: 2030-10-01
• First posted: 2025-11-21
• Last updated: 2025-12-09

Locations

1 site across 1 country: Hong Kong

Regulatory

• FDA-regulated drug study