InfluenzaPhase 4DRIVE IIINCT07240922
The Dynamics of the Immune Responses to Repeat Influenza Vaccination Exposures (DRIVE III) Study
A Phase 4 study testing Live attenuated influenza vaccine and recombinant hemagglutinin influenza vaccine in people with Influenza, run by The University of Hong Kong at 1 site in Hong Kong.
Trial 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… Read more about this study
- Who is it for?
- Ages 22 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Influenza
- What is being tested?
- Live attenuated influenza vaccine and recombinant hemagglutinin influenza vaccine
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 600 participants
- Where
- 1 siteHong Kong
- Study dates
- 1 Oct 2025to 1 Oct 2030
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 22 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- 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
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- 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.
Trial locations and contacts
1 site in 1 country.
Hong Kong1 site
School of Public Health, The University of Hong Kong
Hong Kong, Hong Kong, 00000
About this study
Official title: The Dynamics of the Immune Responses to Repeat Influenza Vaccination Exposures (DRIVE III) Study - a Randomized Controlled Trial
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.
Read the 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
- Being tested
- Live attenuated influenza vaccine, Placebo nasal spray, recombinant hemagglutinin influenza vaccine, Placebo injection
- Keywords
- influenza, vaccination, FluMist, Flublok, immunogenicity
- Medical subject headings
- Influenza, Human
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Live attenuated influenza vaccineBiological
0.2mL nasal spray live attenuated influenza vaccine (FluMist, AstraZeneca)
Placebo nasal sprayBiological
0.2mL saline placebo nasal spray
recombinant hemagglutinin influenza vaccineBiological
0.5mL recombinant hemagglutinin influenza vaccine (Flublok, Sanofi)
Placebo injectionBiological
0.5mL saline placebo injection
| Study group | Role | What they receive |
|---|---|---|
| Arm 1: 4 x FluMist | Experimental | FluMist four times annually Receives: Biological: Live attenuated influenza vaccine; Biological: Placebo injection |
| Arm 2: alternate FluMist and Flublok | Experimental | Alternating FluMist and Flublok annually Receives: 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 Receives: Biological: Placebo nasal spray; Biological: recombinant hemagglutinin influenza vaccine; Biological: Placebo injection |
| Arm 4: 4 x Flublok | Experimental | Flublok four times annually Receives: Biological: Placebo nasal spray; Biological: recombinant hemagglutinin influenza vaccine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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
Measured: 30 days and 182 days
Secondary outcomes (4)
Proportion above 40
The proportion of participants who achieve an HAI titer ≥40 after each vaccination (or neutralization assay for H3N2 and any other non-hemagglutinating strains).
Measured: 30 days
T cell immunity
The vaccine-induced influenza-specific CD4+ and CD8+ T cell responses 7 and 30 days post-vaccination, including cytokine production evaluated by Intracellular Cytokine Staining (ICS) assay. Responses for these and other relevant biomarkers are compared to the corresponding pre-vaccination values for each participant.
Measured: 7 days and 30 days
Adverse events
The rate of adverse events within 30 days after receipt of vaccination or placebo.
Measured: 30 days
Infection rate
The rate of PCR-confirmed influenza virus infection.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Nov 2025
- Study start1 Oct 2025
- Primary completion1 Oct 2030 (estimated)
- Study completion1 Oct 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for InfluenzaStudies of the same condition, open and under way.
- More trials run by The University of Hong KongThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 600 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The University of Hong Kong
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Benjamin J Cowling, PhD, Principal investigator, The University of Hong Kong
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07240922
- Sponsor's protocol ID
- BJC060
- Acronym
- DRIVE III
- Status last verified
- Apr 2026
- First submitted
- 3 Nov 2025
- Last updated
- 15 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: The investigators will share de-identified IPD via github after completion of the study
Study at a glance
From the registry record, last updated by the sponsor on 15 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Dynamics of the Immune Responses to Repeat Influenza Vaccination Exposures (DRIVE III) Study - a Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT07240922
- Acronym / sponsor ID
- DRIVE III / BJC060
- Conditions
- Influenza
- Keywords
- influenza, vaccination, FluMist, Flublok, immunogenicity
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 600 participants (estimated)
- Lead sponsor
- The University of Hong KongUniversity, hospital or other
- Study start
- 1 Oct 2025 (actual)
- Primary completion
- 1 Oct 2030 (estimated)
- Study completion
- 1 Oct 2030 (estimated)
- First posted
- 21 Nov 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Arm 1: 4 x FluMist | Experimental | Biological: Live attenuated influenza vaccine, Biological: Placebo injectionFluMist four times annually |
| Arm 2: alternate FluMist and Flublok | Experimental | Biological: Live attenuated influenza vaccine, Biological: Placebo nasal spray, Biological: recombinant hemagglutinin influenza vaccine, Biological: Placebo injectionAlternating FluMist and Flublok annually |
| Arm 3: alternating Placebo and Flublok | Experimental | Biological: Placebo nasal spray, Biological: recombinant hemagglutinin influenza vaccine, Biological: Placebo injectionAlternating Placebo and Flublok annually |
| Arm 4: 4 x Flublok | Experimental | Biological: Placebo nasal spray, Biological: recombinant hemagglutinin influenza vaccineFlublok four times annually |
Who may qualify
- Ages
- 22 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (15 listed)
- 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:
- Individuals who report medical conditions not suitable to receive live attenuated vaccines, such as:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Live attenuated influenza vaccine0.2mL nasal spray live attenuated influenza vaccine (FluMist, AstraZeneca) | Biological | Arm 1: 4 x FluMist, Arm 2: alternate FluMist and Flublok |
| Placebo nasal spray0.2mL saline placebo nasal spray | Biological | Arm 2: alternate FluMist and Flublok, Arm 3: alternating Placebo and Flublok, Arm 4: 4 x Flublok |
| recombinant hemagglutinin influenza vaccine0.5mL recombinant hemagglutinin influenza vaccine (Flublok, Sanofi) | Biological | Arm 2: alternate FluMist and Flublok, Arm 3: alternating Placebo and Flublok, Arm 4: 4 x Flublok |
| Placebo injection0.5mL saline placebo injection | Biological | Arm 1: 4 x FluMist, Arm 2: alternate FluMist and Flublok, Arm 3: alternating Placebo and Flublok |
Primary outcome
Target rise in HAI titer
Time frame: 30 days
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)
GMT ratio
Time frame: 30 days and 182 days
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.
Detectable mucosal IgG and IgA
Time frame: 30 days and 182 days
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.
Fold rise in mucosal IgA and IgG
Time frame: 30 days
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
GMT ratios of mucosal IgG and IgA
Time frame: 30 days and 182 days
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
4 secondary outcomes
Proportion above 40
Time frame: 30 days
T cell immunity
Time frame: 7 days and 30 days
Adverse events
Time frame: 30 days
Infection rate
Time frame: 1 year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 May 2026.
- Individual participant dataSharing planned: Yes. The investigators will share de-identified IPD via github after completion of the study
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Benjamin J Cowling, PhD principal investigator
The University of Hong Kong
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Live attenuated influenza vaccine and recombinant hemagglutinin influenza vaccine in people with Influenza, run by The University of Hong Kong at 1 site in Hong Kong.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 15 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Hong Kong. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Target rise in HAI titer (time frame: 30 days). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 May 2026.