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

NCT03330132 | Completed Phase 4 DMC

• 1 other identifier: YHT005.1
• Study Type: interventional
• Target: 1,861
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Influenza, Human

Outcome Measures

Primary Outcomes (1)

• Difference in antibody titres

  The difference in antibody titres of participants measured by haemagglutination-inhibition (HAI) assay, evaluated by (1) the proportion of participants who achieve a target rise in antibody titre against each of the vaccine strains at 30 days, and (2) the geometric mean titre (GMT) ratios between the two groups against each of the vaccine strains at 30 days and 182 days. (The targeted rise in antibody titre is defined as the percentage of subjects with either a pre-vaccination HAI titre \<10 and a post-vaccination HAI titre ≥40, or a pre-vaccination HAI titre ≥10 and a minimum four-fold rise in post-vaccination HAI antibody titre.)

  30 and 182 days after each vaccination

Secondary Outcomes (4)

• Seroprotection

  30 days after each vaccination

• CMI responses

  . 7 days after each vaccination

• Adverse events

  30 days after each vaccination

• PCR confirmed infection

  182 days after each vaccination

Study Arms (11)

Standard vaccine

ACTIVE COMPARATOR

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

Biological: Standard inactivated influenza vaccine (NH formulation)

Alternating standard vaccine & adjuvanted vaccine

EXPERIMENTAL

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.

Biological: Standard inactivated influenza vaccine (NH formulation); Biological: MF 59 adjuvanted inactivated influenza vaccine (NH formulation)

Alternating adjuvanted vaccine & standard vaccine

EXPERIMENTAL

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.

Biological: Standard inactivated influenza vaccine (NH formulation); Biological: MF 59 adjuvanted inactivated influenza vaccine (NH formulation)

Alternating standard vaccine and high-dose vaccine

EXPERIMENTAL

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.

Biological: Standard inactivated influenza vaccine (NH formulation); Biological: High-dose inactivated influenza vaccine (NH formulation)

Alternating high-dose vaccine and standard vaccine

EXPERIMENTAL

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.

Biological: Standard inactivated influenza vaccine (NH formulation); Biological: High-dose inactivated influenza vaccine (NH formulation)

Alternating adjuvanted vaccine and high-dose vaccine

EXPERIMENTAL

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.

Biological: MF 59 adjuvanted inactivated influenza vaccine (NH formulation); Biological: High-dose inactivated influenza vaccine (NH formulation)

Alternating high-dose vaccine and adjuvanted vaccine

EXPERIMENTAL

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.

Biological: MF 59 adjuvanted inactivated influenza vaccine (NH formulation); Biological: High-dose inactivated influenza vaccine (NH formulation)

High-dose vaccine

EXPERIMENTAL

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

Biological: High-dose inactivated influenza vaccine (NH formulation)

Adjuvanted vaccine

EXPERIMENTAL

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

Biological: MF 59 adjuvanted inactivated influenza vaccine (NH formulation)

Recombinant vaccine

EXPERIMENTAL

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

Biological: Recombinant hemagglutinin inactivated influenza vaccine (NH formulation)

Alternating recombinant vaccine and adjuvanted vaccine

EXPERIMENTAL

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.

Biological: MF 59 adjuvanted inactivated influenza vaccine (NH formulation); Biological: Recombinant hemagglutinin inactivated influenza vaccine (NH formulation)

Interventions

Standard inactivated influenza vaccine (NH formulation) 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 adjuvanted vaccine & standard vaccine; Alternating high-dose vaccine and standard vaccine; Alternating standard vaccine & adjuvanted vaccine; Alternating standard vaccine and high-dose vaccine; Standard vaccine

MF 59 adjuvanted inactivated influenza vaccine (NH formulation) 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.

Adjuvanted vaccine; Alternating adjuvanted vaccine & standard vaccine; Alternating adjuvanted vaccine and high-dose vaccine; Alternating high-dose vaccine and adjuvanted vaccine; Alternating recombinant vaccine and adjuvanted vaccine; Alternating standard vaccine & adjuvanted vaccine

Recombinant hemagglutinin inactivated influenza vaccine (NH formulation) 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; Recombinant vaccine

High-dose inactivated influenza vaccine (NH formulation) 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 high-dose vaccine and adjuvanted vaccine; Alternating high-dose vaccine and standard vaccine; Alternating standard vaccine and high-dose vaccine; High-dose vaccine

Eligibility Criteria

• Age: 65 Years - 82 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• The University of Hong Kong: lead
• Centers for Disease Control and Prevention: collaborator

Study Sites (1)

The University of Hong Kong

Hong Kong, China

Location

Related Publications (4)

• Daulagala P, Leung YWY, Luk LLH, Ho F, Chu SHN, Lin J, Cheng SMS, Leung NHL, Eichelberger MC, Peiris M, Iuliano AD, Thompson MG, Cowling BJ, Yen HL. Antineuraminidase Antibody Responses in Older Adults After Consecutive Vaccinations With Enhanced Influenza Vaccines: A Randomized Controlled Trial. J Infect Dis. 2026 Apr 29;233(4):e1022-e1030. doi: 10.1093/infdis/jiaf616.

  PMID: 41359521 DERIVED

• 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 Nov 6;81(4):e192-e201. doi: 10.1093/cid/ciaf060.

  PMID: 40178253 DERIVED

• 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.

  PMID: 32407535 DERIVED

• 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.

  PMID: 31828291 DERIVED

MeSH Terms

Conditions

Influenza, Human

Condition Hierarchy (Ancestors)

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

Study Officials

• Benjamin J COWLING, PhD

  The University of Hong Kong

  PRINCIPAL INVESTIGATOR

Study Design

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

Model Details: 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

Study Record Dates

• First Submitted: October 10, 2017
• First Posted: November 6, 2017
• Study Start: October 7, 2017
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: May 15, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

CN (1)