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

NCT07240922 | Recruiting Phase 4 DMC FDA Drug

• 1 other identifier: BJC060
• Study Type: interventional
• Target: 600
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Influenza

Keywords

influenza; vaccination; FluMist; Flublok; immunogenicity

Outcome Measures

Primary Outcomes (5)

• Target rise in HAI titer

  The difference in humoral antibody titers measured by hemagglutination-inhibition (HAI) assay, evaluated by the proportion of participants who achieve a target rise in antibody titre against each of the vaccine strains at 30 days (the targeted rise in antibody titre is defined as the proportion of participants with a four-fold or greater rise in titer, i.e. either a pre-vaccination HAI titer \<10 and a post-vaccination HAI titre ≥20, or a pre-vaccination HAI titer ≥10 and at least a four-fold rise in post-vaccination HAI antibody titer)

  30 days

• GMT ratio

  The difference in humoral antibody titers measured by hemagglutination-inhibition (HAI) assay, evaluated by the geometric mean titer (GMT) ratios between the different groups against each of the vaccine strains at 30 days and 182 days.

  30 days and 182 days

• Detectable mucosal IgG and IgA

  The difference in mucosal antibody titers to the vaccine strains in terms of secretory IgA and IgG measured by ELISA, evaluated by the proportion of participants who show titers above detection threshold.

  30 days and 182 days

• Fold rise in mucosal IgA and IgG

  The difference in mucosal antibody titers to the vaccine strains in terms of secretory IgA and IgG measured by ELISA, evaluated by the proportion of participants who obtain a ≥4-fold rise in IgA and IgG titers

  30 days

• GMT ratios of mucosal IgG and IgA

  The difference in mucosal antibody titers to the vaccine strains in terms of secretory IgA and IgG measured by ELISA, evaluated by the geometric mean titer (GMT) ratios between the different groups against each of the vaccine strains at 30 days and 182 days

  30 days and 182 days

Secondary Outcomes (4)

• Proportion above 40

  30 days

• T cell immunity

  7 days and 30 days

• Adverse events

  30 days

• Infection rate

  1 year

Study Arms (4)

Arm 1: 4 x FluMist

EXPERIMENTAL

FluMist four times annually

Biological: Live attenuated influenza vaccine; Biological: Placebo injection

Arm 2: alternate FluMist and Flublok

EXPERIMENTAL

Alternating FluMist and Flublok annually

Biological: Live attenuated influenza vaccine; Biological: Placebo nasal spray; Biological: recombinant hemagglutinin influenza vaccine; Biological: Placebo injection

Arm 3: alternating Placebo and Flublok

EXPERIMENTAL

Alternating Placebo and Flublok annually

Biological: Placebo nasal spray; Biological: recombinant hemagglutinin influenza vaccine; Biological: Placebo injection

Arm 4: 4 x Flublok

EXPERIMENTAL

Flublok four times annually

Biological: Placebo nasal spray; Biological: recombinant hemagglutinin influenza vaccine

Interventions

Live attenuated influenza vaccine BIOLOGICAL

0.2mL nasal spray live attenuated influenza vaccine (FluMist, AstraZeneca)

Arm 1: 4 x FluMist; Arm 2: alternate FluMist and Flublok

Placebo nasal spray BIOLOGICAL

0.2mL saline placebo nasal spray

Arm 2: alternate FluMist and Flublok; Arm 3: alternating Placebo and Flublok; Arm 4: 4 x Flublok

recombinant hemagglutinin influenza vaccine BIOLOGICAL

0.5mL recombinant hemagglutinin influenza vaccine (Flublok, Sanofi)

Arm 2: alternate FluMist and Flublok; Arm 3: alternating Placebo and Flublok; Arm 4: 4 x Flublok

Placebo injection BIOLOGICAL

0.5mL saline placebo injection

Arm 1: 4 x FluMist; Arm 2: alternate FluMist and Flublok; Arm 3: alternating Placebo and Flublok

Eligibility Criteria

• Age: 22 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Aged 22-50 years at enrolment.
• A. Participated in the DRIVE I or DRIVE II studies (for DRIVE IIIa). OR B. Did not participate in the DRIVE I or DRIVE II study (for DRIVE IIIb) and has not received influenza vaccination in the prior two years.
• Capable of providing informed consent.
• Resident in Hong Kong in the coming 2 years.

You may not qualify if:

• Included in one of the priority groups to receive influenza vaccination in Hong Kong (priority groups include pregnant women, long-stay residents of institutions for persons with disability, persons with chronic medical problems (chronic cardiovascular, lung, metabolic or kidney diseases, obesity (body mass index 30 or above) and chronic neurological condition ), healthcare workers or persons working in poultry, pig farming or pig slaughtering industry).
• With diagnosed medical conditions related to their immune system.
• Currently taking medication for any condition that impairs immune system.
• Individuals who report medical conditions not suitable to receive inactivated influenza vaccines, such as:
• Severe allergic reaction (e.g., anaphylaxis) after previous dose of any influenza vaccine; or to a vaccine component;
• Moderate or severe acute illness with or without fever after any previous influenza vaccination; or
• A history of Guillain-Barré syndrome (GBS) within 6 weeks of previous influenza vaccination.
• Individuals who report medical conditions not suitable to receive live attenuated vaccines, such as:
• having asthma;
• having close contact with severely immunosuppressed persons who require a protected environment; or
• having immunosuppressive treatment (e.g. high-dose steroid, anti-cancer drugs and radiotherapy).
• Individuals who report medical conditions not suitable to receive intramuscular injection, such as
• Bleeding disorders
• Habitually taking anticoagulants (with the exception of antiplatelets such as aspirin).
• Individuals who have any medical conditions not suitable to receive inactivated or live attenuated influenza vaccines as determined by a clinician.

Sponsors & Collaborators

• The University of Hong Kong: lead

Study Sites (1)

School of Public Health, The University of Hong Kong

Hong Kong, 00000, Hong Kong

RECRUITING

MeSH Terms

Conditions

Influenza, Human

Interventions

Influenza Vaccines

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Viral Vaccines; Vaccines; Biological Products; Complex Mixtures

Study Officials

• Benjamin J Cowling, PhD

  The University of Hong Kong

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Benjamin J Cowling, PhD

CONTACT

+852 39176711; bcowling@hku.hk

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 3, 2025
• First Posted: November 21, 2025
• Study Start: October 1, 2025
• Primary Completion (Estimated): October 1, 2030
• Study Completion (Estimated): October 1, 2030
• Last Updated: December 9, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ANALYTIC CODE
• Time Frame: After completion of the study
• Access Criteria: Publicly available via github

Locations

HK (1)