Influenza, HumanPhase 4DRIVENCT04576377
Dynamics of the Immune Responses to Repeat Influenza Vaccination Exposures
A Phase 4 study testing FluBlok in people with Influenza, Human, run by The University of Hong Kong at 1 site in Hong Kong.
Trial summary
The aims of this vaccine trial are: (1) to measure humoral and selected cellular immune responses to repeated influenza vaccination with Flublok, including these responses' associations with age, birth year, and prior vaccination history; (2) to identify the characteristics of study participants who are vaccinated but… Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Influenza, Human
- What is being tested?
- FluBlok
- Type of treatment
- Vaccines
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 977 participants
- Where
- 1 siteHong Kong
- Study dates
- 5 Oct 2020to 31 Dec 2025
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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 18 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Aged 18-45 years at enrolment.
- Capable of providing informed consent.
- Resident in Hong Kong in the coming 2 years.
Who cannot join
- Vaccinated against influenza in the past 24 months.
- 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 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 influenza vaccines as determined by a clinician.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Dynamics of the Immune Responses to Repeat Influenza Vaccination Exposures (DRIVE) Study - a Randomized Controlled Trial
The aims of this vaccine trial are: (1) to measure humoral and selected cellular immune responses to repeated influenza vaccination with Flublok, including these responses' associations with age, birth year, and prior vaccination history; (2) to identify the characteristics of study participants who are vaccinated but still become infected with influenza virus ("vaccine failures") and participants who have poor immune responses to vaccination; and (3) to predict how influenza vaccinations and infections shape immunity.
Read the detailed description
Background: Influenza vaccine is the most frequently used vaccine in the United States and globally. Influenza vaccination provides variable protection against influenza virus infection from year to year, with multiple factors contributing to variation in vaccine effectiveness. First, viral evolution necessitates regular updates to vaccine strains, and the degree of match between vaccine and circulating strains affects vaccine protection. A more serious issue, which motivates this study, is that repeated influenza vaccination may lead to "focusing" of immune responses to older strains, potentially reducing protection against recent strains.
Aims and objectives: The aims of this trial are: (1) to measure humoral and selected cellular immune responses to repeated influenza vaccination, including these responses' associations with age, birth year, and prior vaccination history; (2) to identify the characteristics of study participants who are vaccinated but still become infected with influenza virus ("vaccine failures"); and (3) to predict how influenza vaccinations and infections shape immunity.
Study design: *DRIVE I* A 4-year immunogenicity study with a randomized controlled design including 447 adults who are 18-45 years of age. Participants will be randomized to 5 groups in equal proportions, where the groups receive Flublok (Sanofi Pasteur) vaccine (V) or saline placebo (P) in years 1-4: group 1: V+V+V+V; group 2: P+V+V+V; group 3: P+P+V+V; group 4: P+P+P+V; group 5: P+P+P+P.
*DRIVE II* A 3-year and one-month immunogenicity study with a randomized controlled design among 530 adults who are 18-45 years of age. Participants will be randomized into 4 groups in equal proportions, where the groups will receive Flublok (Sanofi Pasteur) vaccine (V) or saline placebo (P) in year 1-4: group 1: V+V+V+V; group 2: P+V+V+V; group 3: P+P+V+V; group 4: P+P+P+V.
*DRIVE I \& DRIVE II* All participants will receive influenza vaccination at the end of the final year. We will collect blood samples and nasal strip samples before vaccination and various timepoints after vaccination. Whole blood samples will be collected from a subset for later PBMC analysis. We will actively monitor participants for acute respiratory illnesses throughout the follow-up period, and collect and test respiratory swabs and blood samples to identify respiratory virus infections and acute immune responses to infection.
Number of Subjects: DRIVE I: 447 enrolled in autumn and winter 2020/21. DRIVE II: 530 enrolled in autumn and winter 2021/22.
Main outcome measures: The primary outcome measures are the humoral immune responses at day 30 after vaccination measured by hemagglutinin inhibition and microneutralization assays. The investigators will also study a number of secondary outcomes, including the persistence of immune responses 91, 182, 273 and 365 days after vaccination, and the immune responses to natural laboratory-confirmed influenza virus infections, as well as immunity and immune responses to other respiratory viruses including COVID-19 (SARS-CoV- 2).
Potential implications: Our study will provide novel insight into the effects of repeat influenza vaccination and infection 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, Human
- Being tested
- FluBlok, Placebo
- Medical subject headings
- Influenza, Human
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FluBlokBiological
Recombinant HA quadrivalent influenza vaccine (0.5mL Flublok®, Sanofi Pasteur) containing 180μg antigen, 45μg for each influenza strain included.
PlaceboOther
0.5mL saline placebo.
| Study group | Role | What they receive |
|---|---|---|
| Influenza vaccination | Experimental | Not described Receives: Biological: FluBlok |
| Placebo | Placebo comparator | Not described Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Immune response to vaccination (4-fold rise in titer at day 30)
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 hemagglutination inhibition titer <10 and a post-vaccination hemagglutination inhibition titre ≥20, or a pre- vaccination hemagglutination inhibition titer ≥10 and at least a four-fold rise in post-vaccination hemagglutination inhibition antibody titer). The HAI assay has been unreliable for recent influenza A(H3N2) viruses, and if the vaccine strains or circulating strains in our study have this property we will use neutralization assays in place of HAI assays for the primary outcome for A(H3N2). Similarly, neutralization assays will be used if other influenza strains fail to hemagglutinate in the future.
Measured: 30 days after vaccination
Immune response to vaccination (GMT ratio at day 30 and 182)
The geometric mean titer (GMT) ratios between the vaccine group and the comparator group (placebo) against each of the vaccine strains at 30 days and 182 days
Measured: 30 days and 182 days after vaccination
Secondary outcomes (6)
Immune response to vaccination (antibody titer >=40 at day 30 and 182)
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 and 182 days after vaccination
Immune response to vaccination (cell-mediated 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 after vaccination
Immune response to vaccination (antibody specificity)
The fine-grained specificity and phenotypes of antibodies and influenza-positive B and T cell populations before and after vaccination and natural infection.
Measured: 30 days and 182 days after vaccination
Incidence of reactions after vaccination [Safety]
The rate of adverse events within 30 days after receipt of vaccination or placebo
Measured: 30 days after vaccination
Incidence of laboratory-confirmed influenza after vaccination (vaccine failure)
The rate of polymerase chain reaction (PCR)-confirmed influenza virus infection.
Measured: One year after vaccination
Incidence of other respiratory infections
The occurrence of other respiratory infections, including COVID-19 infections, in participants, determined by PCR or serology
Measured: One year after vaccination
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Oct 2020
- Study start5 Oct 2020
- Primary completion31 Dec 2025
- Study completion31 Dec 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Influenza, HumanStudies 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
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 977 participants (actual)
Sponsor and investigators
- Lead sponsor
- The University of Hong Kong
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04576377
- Sponsor's protocol ID
- BJC033
- Other IDs
- 1U01AI153700
- Acronym
- DRIVE
- Status last verified
- Apr 2026
- First submitted
- 29 Sep 2020
- Last updated
- 15 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: We will release anonymized individual patient data along with publication of study results.
Publications
Cowling BJ, Wong SS, Santos JJS, Touyon L, Ort JT, Ye N, Kwok NKM, Ho F, Cheng SMS, Ip DKM, Peiris M, Webby RJ, Wilson PC, Valkenburg SA, Tsang JS, Leung NHL, Hensley SE, Cobey S. Preliminary Findings From the Dynamics of the Immune Responses to Repeat Influenza Vaccination Exposures (DRIVE I) Study: A Randomized Controlled Trial. Clin Infect Dis. 2024 Oct 15;79(4):901-909. doi: 10.1093/cid/ciae380.
PubMed 39041887
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) Study - a Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT04576377
- Acronym / sponsor ID
- DRIVE / BJC033
- Conditions
- Influenza, Human
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 977 participants (actual)
- Lead sponsor
- The University of Hong KongUniversity, hospital or other
- Collaborators
- University of Chicago, National Institute of Allergy and Infectious Diseases (NIAID)
- Study start
- 5 Oct 2020 (actual)
- Primary completion
- 31 Dec 2025 (actual)
- Study completion
- 31 Dec 2025 (actual)
- First posted
- 6 Oct 2020 (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.
The aims of this vaccine trial are: (1) to measure humoral and selected cellular immune responses to repeated influenza vaccination with Flublok, including these responses' associations with age, birth year, and prior vaccination history; (2) to identify the characteristics of study participants who are vaccinated but still become infected with influenza virus ("vaccine failures") and participants who have poor immune responses to vaccination; and (3) to predict how influenza vaccinations and infections shape immunity.
Detailed description
Background: Influenza vaccine is the most frequently used vaccine in the United States and globally. Influenza vaccination provides variable protection against influenza virus infection from year to year, with multiple factors contributing to variation in vaccine effectiveness. First, viral evolution necessitates regular updates to vaccine strains, and the degree of match between vaccine and circulating strains affects vaccine protection. A more serious issue, which motivates this study, is that repeated influenza vaccination may lead to "focusing" of immune responses to older strains, potentially reducing protection against recent strains.
Aims and objectives: The aims of this trial are: (1) to measure humoral and selected cellular immune responses to repeated influenza vaccination, including these responses' associations with age, birth year, and prior vaccination history; (2) to identify the characteristics of study participants who are vaccinated but still become infected with influenza virus ("vaccine failures"); and (3) to predict how influenza vaccinations and infections shape immunity.
Study design: *DRIVE I* A 4-year immunogenicity study with a randomized controlled design including 447 adults who are 18-45 years of age. Participants will be randomized to 5 groups in equal proportions, where the groups receive Flublok (Sanofi Pasteur) vaccine (V) or saline placebo (P) in years 1-4: group 1: V+V+V+V; group 2: P+V+V+V; group 3: P+P+V+V; group 4: P+P+P+V; group 5: P+P+P+P.
*DRIVE II* A 3-year and one-month immunogenicity study with a randomized controlled design among 530 adults who are 18-45 years of age. Participants will be randomized into 4 groups in equal proportions, where the groups will receive Flublok (Sanofi Pasteur) vaccine (V) or saline placebo (P) in year 1-4: group 1: V+V+V+V; group 2: P+V+V+V; group 3: P+P+V+V; group 4: P+P+P+V.
*DRIVE I \& DRIVE II* All participants will receive influenza vaccination at the end of the final year. We will collect blood samples and nasal strip samples before vaccination and various timepoints after vaccination. Whole blood samples will be collected from a subset for later PBMC analysis. We will actively monitor participants for acute respiratory illnesses throughout the follow-up period, and collect and test respiratory swabs and blood samples to identify respiratory virus infections and acute immune responses to infection.
Number of Subjects: DRIVE I: 447 enrolled in autumn and winter 2020/21. DRIVE II: 530 enrolled in autumn and winter 2021/22.
Main outcome measures: The primary outcome measures are the humoral immune responses at day 30 after vaccination measured by hemagglutinin inhibition and microneutralization assays. The investigators will also study a number of secondary outcomes, including the persistence of immune responses 91, 182, 273 and 365 days after vaccination, and the immune responses to natural laboratory-confirmed influenza virus infections, as well as immunity and immune responses to other respiratory viruses including COVID-19 (SARS-CoV- 2).
Potential implications: Our study will provide novel insight into the effects of repeat influenza vaccination and infection 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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Influenza vaccination | Experimental | Biological: FluBlok |
| Placebo | Placebo comparator | Other: Placebo |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Aged 18-45 years at enrolment.
- Capable of providing informed consent.
- Resident in Hong Kong in the coming 2 years.
Key exclusion criteria (7 listed)
- Vaccinated against influenza in the past 24 months.
- 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.
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 |
|---|---|---|
| FluBlokRecombinant HA quadrivalent influenza vaccine (0.5mL Flublok®, Sanofi Pasteur) containing 180μg antigen, 45μg for each influenza strain included. | Biological | Influenza vaccination |
| Placebo0.5mL saline placebo. | Other | Placebo |
Primary outcome
Immune response to vaccination (4-fold rise in titer at day 30)
Time frame: 30 days after vaccination
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 hemagglutination inhibition titer <10 and a post-vaccination hemagglutination inhibition titre ≥20, or a pre- vaccination hemagglutination inhibition titer ≥10 and at least a four-fold rise in post-vaccination hemagglutination inhibition antibody titer). The HAI assay has been unreliable for recent influenza A(H3N2) viruses, and if the vaccine strains or circulating strains in our study have this property we will use neutralization assays in place of HAI assays for the primary outcome for A(H3N2). Similarly, neutralization assays will be used if other influenza strains fail to hemagglutinate in the future.
Immune response to vaccination (GMT ratio at day 30 and 182)
Time frame: 30 days and 182 days after vaccination
The geometric mean titer (GMT) ratios between the vaccine group and the comparator group (placebo) against each of the vaccine strains at 30 days and 182 days
6 secondary outcomes
Immune response to vaccination (antibody titer >=40 at day 30 and 182)
Time frame: 30 days and 182 days after vaccination
Immune response to vaccination (cell-mediated immunity)
Time frame: 7 days and 30 days after vaccination
Immune response to vaccination (antibody specificity)
Time frame: 30 days and 182 days after vaccination
Incidence of reactions after vaccination [Safety]
Time frame: 30 days after vaccination
Incidence of laboratory-confirmed influenza after vaccination (vaccine failure)
Time frame: One year after vaccination
Incidence of other respiratory infections
Time frame: One year after vaccination
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 May 2026.
- Derived from this study: PubMed 39041887Cowling BJ, Wong SS, Santos JJS, Touyon L, Ort JT, Ye N, Kwok NKM, Ho F, Cheng SMS, Ip DKM, Peiris M, Webby RJ, Wilson PC, Valkenburg SA, Tsang JS, Leung NHL, Hensley SE, Cobey S. Preliminary Findings From the Dynamics of the Immune Responses to Repeat Influenza Vaccination Exposures (DRIVE I) Study: A Randomized Controlled Trial. Clin Infect Dis. 2024 Oct 15;79(4):901-909. doi: 10.1093/cid/ciae380.
- Individual participant dataSharing planned: Yes. We will release anonymized individual patient data along with publication of study results.
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 FluBlok in people with Influenza, Human, 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 3 inclusion and 7 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: finished, 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. Some participants in this study may receive a placebo. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Immune response to vaccination (4-fold rise in titer at day 30) (time frame: 30 days after vaccination). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04576377, which also lists 1 linked publication.
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.