Immunogenicity of Twice-annual Influenza Vaccination in Older Adults in Hong Kong

NCT ID: NCT02957890

Last Updated: 2023-12-11

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 400 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-11-18
• Study Completion Date: 2026-09-30

Brief Summary

This study evaluates the immunogenicity of adding inactivated influenza vaccine with southern hemisphere (SH) formulation to standard once-annual influenza vaccination with northern hemisphere (NH) formulation in older adults in Hong Kong over 9 years. Half of participants will receive twice-annual influenza vaccination with NH and SH formulation, while the other half will receive once-annual influenza vaccination with NH formulation and a placebo.

Detailed Description

Background: Hong Kong is located in subtropical regions with two seasonal peaks of influenza transmission. North Hemisphere seasonal influenza vaccine is usually available for vaccination by general public starting in October every year before the anticipated winter peak starting in December in Hong Kong, and it presumably also provides protection against the same prevailing strains during summer peak starting around July of the next year. However, influenza vaccines may have poorer efficacy and effectiveness in older adults. The investigators hypothesize that in a subtropical or tropical location with prolonged circulation of influenza viruses, including the emergence of new strains at different times of the year, twice-annual vaccination with the latest available strains could provide the best protection.

Aim: To test the immune profiles over time of older adults following twice-annual influenza vaccination against those receiving once-annual influenza vaccination.

Design and subjects: An immunogenicity study with a randomized placebo-controlled design among 400 older adults aged 70-79 years. The investigators will enroll participants from the general community who attend general outpatient clinics for influenza vaccination or medical or preventive care visits. Eligible individuals will be randomly allocated in equal proportions to two intervention groups (I: once-annual standard inactivated influenza vaccine; II: twice-annual standard inactivated influenza vaccine) consisting of ten rounds of vaccination as designated by the intervention group before each winter/summer influenza season and followed throughout the 5 years. *In August 2021 we extended the study for a further 4 years (9 years in total) through to August 2025, with the same study design.* Before each summer influenza season those in group II will receive the inactivated influenza vaccine with the southern hemisphere formulation and the other group will receive saline placebo. For each round of vaccination (or placebo), blood samples for immunological tests will be collected before administration and 30 days after administration among all participants, and at 7, 30 and 91 days after administration in a subset of 25% of the participants. Acute illnesses among participants will be monitored by active surveillance during influenza seasons. The vaccine formulations in each round of vaccination will be updated for each season according to WHO recommendations.

Main outcome measures: Antibody titres 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 two intervention groups each round.

Conditions

Influenza, Human

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: TRIPLE

Study Groups

Twice-annual influenza vaccination

Twice-annual influenza vaccination: administrations of inactivated influenza vaccine (Northern hemisphere formulation, NH) prior to the northern hemisphere winter, plus inactivated influenza vaccine (Southern hemisphere formulation, SH) prior to the northern hemisphere summer.

Group Type: EXPERIMENTAL

Inactivated influenza vaccine (NH formulation)

Intervention Type: BIOLOGICAL

Round 1 (November): 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

Inactivated influenza vaccine (SH formulation)

Intervention Type: BIOLOGICAL

Round 2 (May): 0.5mL Vaxigrip®, Sanofi Pasteur, containing 45μg antigen - 15μg for each influenza strain included - with strains recommended by the WHO for the southern hemisphere formulation

Once-annual influenza vaccination

Administrations of inactivated influenza vaccine (Northern hemisphere formulation, NH) prior to the northern hemisphere winter, plus placebo prior to the northern hemisphere summer.

Group Type: PLACEBO_COMPARATOR

Inactivated influenza vaccine (NH formulation)

Intervention Type: BIOLOGICAL

Round 1 (November): 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

Placebo

Intervention Type: BIOLOGICAL

Round 2 (May): 0.5mL normal saline

Interventions

Inactivated influenza vaccine (NH formulation)

Round 1 (November): 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

Inactivated influenza vaccine (SH formulation)

Round 2 (May): 0.5mL Vaxigrip®, Sanofi Pasteur, containing 45μg antigen - 15μg for each influenza strain included - with strains recommended by the WHO for the southern hemisphere formulation

Intervention Type: BIOLOGICAL

Placebo

Round 2 (May): 0.5mL normal saline

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• Adult aged 70-79 years attending GOPCs, DECCs or day care centres for receiving influenza vaccination or medical or preventive care visits.

Exclusion Criteria

• Individuals who show signs of dementia (either confirmed by medical records or do not pass the Mini-cog test) 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, according to medical record, 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: 70 Years
• Maximum Eligible Age: 79 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Centers for Disease Control and Prevention

FED

Sponsor Role: collaborator

Hospital Authority, Hong Kong

OTHER_GOV

Sponsor Role: collaborator

The University of Hong Kong

OTHER

Sponsor Role: lead

Responsible Party

Dr. Benjamin John Cowling

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Benjamin COWLING, PhD

Role: PRINCIPAL_INVESTIGATOR

The University of Hong Kong

Locations

The University of Hong Kong

Hong Kong, , China

Countries

China

Other Identifiers

YHT004.5

Identifier Type: -

Identifier Source: org_study_id