Immunogenicity of Alternative Annual Influenza Vaccination Strategies in Older Adults in Hong Kong

NCT ID: NCT03330132

Last Updated: 2023-12-11

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE4

Total Enrollment

1861 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-10-07

Study Completion Date

2026-12-31

Brief Summary

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This study allows to evaluate the strength and duration of immune responses between annual receipt of standard inactivated vaccine and alternative potent vaccines, including annual receipt of adjuvanted inactivated vaccine, annual receipt of high-dose inactivated vaccine, annual receipt of recombinant HA vaccine, and the alternate combinations of the former three vaccines over four years, for identifying improved vaccination strategies for influenza vaccination in older adults in a location experiencing a subtropical pattern in influenza activity.

Detailed Description

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Background: The typical vaccination strategy of annual administration with inactivated trivalent influenza vaccine (TIV) or quadrivalent influenza vaccine (QIV) may provide suboptimal protection to older adults in a location with prolonged periods of influenza activity because of the weaker immune response of older adults to vaccination and because of post-vaccination waning in protection over the course of a year. We hypothesize that in a subtropical or tropical location with prolonged circulation of influenza viruses, the higher antibody titers over years achieved after receipt of annual high-dose vaccine, MF59-adjuvanted vaccine or recombinant haemagglutinin (HA) vaccine, or different vaccination strategies of their combinations with or without the standard vaccine, might lead to greater protection than annual receipt of standard vaccines.

Aim: To test the immune profiles over time of older adults following different influenza vaccination strategies.

Design and subjects: Initially a 4-year immunogenicity study with a randomized controlled design among 2200 older adults aged 65-82 years. We will enroll participants who are willing to receive annual influenza vaccination from the general community including community centres and day-care centres. Eligible individuals will be randomly allocated to ten intervention groups (i.e. annual standard QIV, annual MF59-adjuvanted TIV, annual high-dose TIV, annual recombinant-HA QIV, and six combinations of their alternate annual use) consisting of four rounds of vaccination before each winter influenza season and followed up for 4 years. For each round of vaccination, blood samples for immunological tests will be collected before vaccination and 30 and 182 days after vaccination in all participants, and also at 7, 91 and 273 days after vaccination in a subset of 10% of the participants. Acute illnesses among participants will be monitored by active surveillance efforts during influenza seasons. The vaccine formulation in each round of vaccination will be updated for each season according to WHO recommendations.

Study extension: In years 5-8, all participants will receive the recombinant-HA QIV once per year before each winter influenza season, and their receipt of COVID-19 vaccines will also be recorded. Samples will be collected at the same timepoints to monitor immune responses to influenza vaccination and how responses are affected by prior vaccination history.

Main outcome measures: Antibody titers measured by haemagglutination-inhibition assays, which is an established correlate of protection, in addition to other measurements on humoral and cell-mediated immune responses in the ten intervention groups each year.

Conditions

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Influenza, Human

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Annual vaccination with standard influenza vaccine or enhanced influenza vaccine, including some combination strategies (alternating each year) and some strategies with the same vaccine administered each year
Primary Study Purpose

PREVENTION

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors

Study Groups

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Standard vaccine

Once-annual administration of standard vaccine (northern hemisphere formulation) prior to the northern hemisphere winter throughout 4 years study period.

Group Type ACTIVE_COMPARATOR

Standard inactivated influenza vaccine (NH formulation)

Intervention Type BIOLOGICAL

0.5mL FluQuadri®, Sanofi Pasteur, containing 60μg antigen - 15μg for each influenza strain included - with strains recommended by the WHO for the northern hemisphere formulation.

Alternating standard vaccine & adjuvanted vaccine

Alternating once-annual administration of standard inactivated influenza vaccine (northern hemisphere formulation) prior to the northern hemisphere winter, and once-annual administration of MF59 adjuvanted inactivated influenza vaccine (northern hemisphere formulation) prior to the northern hemisphere winter throughout 4 years study period.

Group Type EXPERIMENTAL

Standard inactivated influenza vaccine (NH formulation)

Intervention Type BIOLOGICAL

0.5mL FluQuadri®, Sanofi Pasteur, containing 60μg antigen - 15μg for each influenza strain included - with strains recommended by the WHO for the northern hemisphere formulation.

MF 59 adjuvanted inactivated influenza vaccine (NH formulation)

Intervention Type BIOLOGICAL

0.5mL FLUAD(TM), Seqirus containing 45μg antigen; 15μg for each influenza strain included and MF59C.1 adjuvant (MF59®) with strains recommended by the WHO for the northern hemisphere formulation.

Alternating adjuvanted vaccine & standard vaccine

Alternating once-annual administration of MF59 adjuvanted inactivated influenza vaccine (northern hemisphere formulation) prior to the northern hemisphere winter, and once-annual administration of standard inactivated influenza vaccine (northern hemisphere formulation) prior to the northern hemisphere winter throughout 4 years study period.

Group Type EXPERIMENTAL

Standard inactivated influenza vaccine (NH formulation)

Intervention Type BIOLOGICAL

0.5mL FluQuadri®, Sanofi Pasteur, containing 60μg antigen - 15μg for each influenza strain included - with strains recommended by the WHO for the northern hemisphere formulation.

MF 59 adjuvanted inactivated influenza vaccine (NH formulation)

Intervention Type BIOLOGICAL

0.5mL FLUAD(TM), Seqirus containing 45μg antigen; 15μg for each influenza strain included and MF59C.1 adjuvant (MF59®) with strains recommended by the WHO for the northern hemisphere formulation.

Alternating standard vaccine and high-dose vaccine

Alternating once-annual administration of standard inactivated influenza vaccine (northern hemisphere formulation) prior to the northern hemisphere winter, and once-annual administration of high-dose inactivated influenza vaccine (northern hemisphere formulation) prior to the northern hemisphere winter throughout 4 years study period.

Group Type EXPERIMENTAL

Standard inactivated influenza vaccine (NH formulation)

Intervention Type BIOLOGICAL

0.5mL FluQuadri®, Sanofi Pasteur, containing 60μg antigen - 15μg for each influenza strain included - with strains recommended by the WHO for the northern hemisphere formulation.

High-dose inactivated influenza vaccine (NH formulation)

Intervention Type BIOLOGICAL

0.5mL Fluzone® High-Dose, Sanofi Pasteur containing 180μg antigen; 60μg for each influenza strain included with strains recommended by the WHO for the northern hemisphere formulation.

Alternating high-dose vaccine and standard vaccine

Alternating once-annual administration of high-dose inactivated influenza vaccine (northern hemisphere formulation) prior to the northern hemisphere winter, and once-annual administration of standard inactivated influenza vaccine (northern hemisphere formulation) prior to the northern hemisphere winter throughout 4 years study period.

Group Type EXPERIMENTAL

Standard inactivated influenza vaccine (NH formulation)

Intervention Type BIOLOGICAL

0.5mL FluQuadri®, Sanofi Pasteur, containing 60μg antigen - 15μg for each influenza strain included - with strains recommended by the WHO for the northern hemisphere formulation.

High-dose inactivated influenza vaccine (NH formulation)

Intervention Type BIOLOGICAL

0.5mL Fluzone® High-Dose, Sanofi Pasteur containing 180μg antigen; 60μg for each influenza strain included with strains recommended by the WHO for the northern hemisphere formulation.

Alternating adjuvanted vaccine and high-dose vaccine

Alternating once-annual administration of MF59 adjuvanted inactivated influenza vaccine (northern hemisphere formulation) prior to the northern hemisphere winter, and once-annual administration of high-dose inactivated influenza vaccine (northern hemisphere formulation) prior to the northern hemisphere winter throughout 4 years study period.

Group Type EXPERIMENTAL

MF 59 adjuvanted inactivated influenza vaccine (NH formulation)

Intervention Type BIOLOGICAL

0.5mL FLUAD(TM), Seqirus containing 45μg antigen; 15μg for each influenza strain included and MF59C.1 adjuvant (MF59®) with strains recommended by the WHO for the northern hemisphere formulation.

High-dose inactivated influenza vaccine (NH formulation)

Intervention Type BIOLOGICAL

0.5mL Fluzone® High-Dose, Sanofi Pasteur containing 180μg antigen; 60μg for each influenza strain included with strains recommended by the WHO for the northern hemisphere formulation.

Alternating high-dose vaccine and adjuvanted vaccine

Alternating once-annual administration of high-dose inactivated influenza vaccine (northern hemisphere formulation) prior to the northern hemisphere winter, and once-annual administration of MF59 adjuvanted inactivated influenza vaccine (northern hemisphere formulation) prior to the northern hemisphere winter throughout 4 years study period.

Group Type EXPERIMENTAL

MF 59 adjuvanted inactivated influenza vaccine (NH formulation)

Intervention Type BIOLOGICAL

0.5mL FLUAD(TM), Seqirus containing 45μg antigen; 15μg for each influenza strain included and MF59C.1 adjuvant (MF59®) with strains recommended by the WHO for the northern hemisphere formulation.

High-dose inactivated influenza vaccine (NH formulation)

Intervention Type BIOLOGICAL

0.5mL Fluzone® High-Dose, Sanofi Pasteur containing 180μg antigen; 60μg for each influenza strain included with strains recommended by the WHO for the northern hemisphere formulation.

High-dose vaccine

Once-annual administration of high-dose inactivated influenza vaccine (northern hemisphere formulation) prior to the northern hemisphere winter throughout 4 years study period.

Group Type EXPERIMENTAL

High-dose inactivated influenza vaccine (NH formulation)

Intervention Type BIOLOGICAL

0.5mL Fluzone® High-Dose, Sanofi Pasteur containing 180μg antigen; 60μg for each influenza strain included with strains recommended by the WHO for the northern hemisphere formulation.

Adjuvanted vaccine

Once-annual administration of MF59 adjuvanted inactivated influenza vaccine (northern hemisphere formulation) prior to the northern hemisphere winter throughout 4 years study period.

Group Type EXPERIMENTAL

MF 59 adjuvanted inactivated influenza vaccine (NH formulation)

Intervention Type BIOLOGICAL

0.5mL FLUAD(TM), Seqirus containing 45μg antigen; 15μg for each influenza strain included and MF59C.1 adjuvant (MF59®) with strains recommended by the WHO for the northern hemisphere formulation.

Recombinant vaccine

Once-annual administration of recombinant hemagglutinin inactivated influenza vaccine (northern hemisphere formulation) prior to the northern hemisphere winter throughout 4 years study period.

Group Type EXPERIMENTAL

Recombinant hemagglutinin inactivated influenza vaccine (NH formulation)

Intervention Type BIOLOGICAL

0.5mL Flublok®, Protein Sciences Corporation containing 180μg antigen, 45μg for each influenza strain included with strains recommended by the WHO for the northern hemisphere formulation.

Alternating recombinant vaccine and adjuvanted vaccine

Alternating once-annual administration of recombinant hemagglutinin inactivated influenza vaccine (northern hemisphere formulation) prior to the northern hemisphere winter, and once-annual administration of MF59 adjuvanted inactivated influenza vaccine (northern hemisphere formulation) prior to the northern hemisphere winter throughout 4 years study period.

Group Type EXPERIMENTAL

MF 59 adjuvanted inactivated influenza vaccine (NH formulation)

Intervention Type BIOLOGICAL

0.5mL FLUAD(TM), Seqirus containing 45μg antigen; 15μg for each influenza strain included and MF59C.1 adjuvant (MF59®) with strains recommended by the WHO for the northern hemisphere formulation.

Recombinant hemagglutinin inactivated influenza vaccine (NH formulation)

Intervention Type BIOLOGICAL

0.5mL Flublok®, Protein Sciences Corporation containing 180μg antigen, 45μg for each influenza strain included with strains recommended by the WHO for the northern hemisphere formulation.

Interventions

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Standard inactivated influenza vaccine (NH formulation)

0.5mL FluQuadri®, Sanofi Pasteur, containing 60μg antigen - 15μg for each influenza strain included - with strains recommended by the WHO for the northern hemisphere formulation.

Intervention Type BIOLOGICAL

MF 59 adjuvanted inactivated influenza vaccine (NH formulation)

0.5mL FLUAD(TM), Seqirus containing 45μg antigen; 15μg for each influenza strain included and MF59C.1 adjuvant (MF59®) with strains recommended by the WHO for the northern hemisphere formulation.

Intervention Type BIOLOGICAL

High-dose inactivated influenza vaccine (NH formulation)

0.5mL Fluzone® High-Dose, Sanofi Pasteur containing 180μg antigen; 60μg for each influenza strain included with strains recommended by the WHO for the northern hemisphere formulation.

Intervention Type BIOLOGICAL

Recombinant hemagglutinin inactivated influenza vaccine (NH formulation)

0.5mL Flublok®, Protein Sciences Corporation containing 180μg antigen, 45μg for each influenza strain included with strains recommended by the WHO for the northern hemisphere formulation.

Intervention Type BIOLOGICAL

Eligibility Criteria

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Inclusion Criteria

• Adult aged 65-82 years attending ECC and EDC who has not received 2017/18 seasonal influenza vaccine and is willing to receive annual influenza vaccination

Exclusion Criteria

* Individuals who show signs of dementia (do not pass the Mini-cog test under Appendix 1a: Recruitment Screening Log) or significant cognitive impairment and are not competent to give their consent.
* 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, including egg protein;
* 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.
Minimum Eligible Age

65 Years

Maximum Eligible Age

82 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Centers for Disease Control and Prevention

FED

Sponsor Role collaborator

The University of Hong Kong

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Benjamin J COWLING, PhD

Role: PRINCIPAL_INVESTIGATOR

The University of Hong Kong

Locations

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The University of Hong Kong

Hong Kong, , China

Site Status

Countries

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China

References

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Fox A, Sanchez-Ovando S, Carolan L, Hadiprodjo AJ, Chen Y, Ho F, Cheng SMS, Thompson MG, Iuliano AD, Levine MZ, Valkenburg SA, Ip DKM, Peiris JSM, Sullivan SG, Cowling BJ, Leung NHL. Enhanced Influenza Vaccines Extend A(H3N2) Antibody Reactivity in Older Adults but Prior Vaccination Effects Persist. Clin Infect Dis. 2025 Apr 3:ciaf060. doi: 10.1093/cid/ciaf060. Online ahead of print.

Reference Type DERIVED
PMID: 40178253 (View on PubMed)

Cowling BJ, Thompson MG, Ng TWY, Fang VJ, Perera RAPM, Leung NHL, Chen Y, So HC, Ip DKM, Iuliano AD. Comparative Reactogenicity of Enhanced Influenza Vaccines in Older Adults. J Infect Dis. 2020 Sep 14;222(8):1383-1391. doi: 10.1093/infdis/jiaa255.

Reference Type DERIVED
PMID: 32407535 (View on PubMed)

Cowling BJ, Perera RAPM, Valkenburg SA, Leung NHL, Iuliano AD, Tam YH, Wong JHF, Fang VJ, Li APY, So HC, Ip DKM, Azziz-Baumgartner E, Fry AM, Levine MZ, Gangappa S, Sambhara S, Barr IG, Skowronski DM, Peiris JSM, Thompson MG. Comparative Immunogenicity of Several Enhanced Influenza Vaccine Options for Older Adults: A Randomized, Controlled Trial. Clin Infect Dis. 2020 Oct 23;71(7):1704-1714. doi: 10.1093/cid/ciz1034.

Reference Type DERIVED
PMID: 31828291 (View on PubMed)

Other Identifiers

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YHT005.1

Identifier Type: -

Identifier Source: org_study_id