Immunogenicity Trial of 3 Influenza Vaccines

NCT05479370 | Completed Phase 3 FDA Drug

• 1 other identifier: 2022/00275
• Study Type: interventional
• Target: 366
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a prospective randomised trial of 3 influenza vaccine formulations with different manufacturing processes: 1) egg-grown (QIV-E); 2) cell-grown (QIV-C); and 3) recombinant protein (QIV-R). The main objective is to compare the antibody responses following influenza vaccination among these 3 vaccines to determine whether recombinant vaccines offer superior protection over standard egg or cell-based formulations. The attenuating effects of prior vaccination on vaccine immunogenicity will also be evaluated. Hypothesis: Vaccination with recombinant vaccine results in better antibody responses, particularly against A(H3N2) viruses, than either standard egg-grown vaccines or cell-grown vaccines.

Conditions

Influenza Vaccination

Keywords

Humoral immunity; Antibody; Vaccination history; B cell response; Vaccine efficacy

Outcome Measures

Primary Outcomes (1)

• Antibody titres against the 4 vaccine antigens

  Post-vaccination geometric mean titre in each vaccination group as measured by the haemagglutination inhibition assay, adjusted for vaccination history and baseline titre.

  Day 0, 14, 150, 330

Secondary Outcomes (9)

• Pre- to post-vaccination antibody titre ratio between vaccination groups

  Day 0, 14, 150, 330

• Range of influenza A(H3N2) strains recognized by the antibodies

  Day 0, 14, 150, 330

• Attenuating effects of prior vaccination on antibody titres

  Day 0, 14, 150, 330

• Attenuating effects of prior vaccination on vaccine immunogenicity

  Day 0, 14, 150, 330

• Long-term humoral immunity

  Day 0, 14, 150, 330

Study Arms (6)

Frequently vaccinated Group 1: QIV-R

EXPERIMENTAL

Frequently vaccinated participants (3 or more influenza vaccinations during the preceding 5 years) received a 0.5mL dose of Flublok Quadrivalent vaccine, intra-muscularly, at Day 0.

Biological: Flublok Quadrivalent vaccine

Frequently vaccinated Group 2: QIV-E

EXPERIMENTAL

Frequently vaccinated participants (3 or more influenza vaccinations during the preceding 5 years) received a 0.5mL dose of Fluarix Quadrivalent vaccine, intra-muscularly, at Day 0.

Biological: Fluarix Quadrivalent vaccine

Frequently vaccinated Group 3: QIV-C

EXPERIMENTAL

Frequently vaccinated participants (3 or more influenza vaccinations during the preceding 5 years) received a 0.5mL dose of Flucelvax Quadrivalent vaccine, intra-muscularly, at Day 0.

Biological: Flucelvax Quadrivalent vaccine

Infrequently vaccinated Group 4: QIV-R

EXPERIMENTAL

Infrequently vaccinated participants (0 or 1 influenza vaccination during the preceding 5 years) received a 0.5mL dose of Flublok Quadrivalent vaccine, intra-muscularly, at Day 0.

Biological: Flublok Quadrivalent vaccine

Infrequently vaccinated Group 5: QIV-E

EXPERIMENTAL

Infrequently vaccinated participants (0 or 1 influenza vaccination during the preceding 5 years) received a 0.5mL dose of Fluarix Quadrivalent vaccine, intra-muscularly, at Day 0.

Biological: Fluarix Quadrivalent vaccine

Infrequently vaccinated Group 6: QIV-C

EXPERIMENTAL

Infrequently vaccinated participants (0 or 1 influenza vaccination during the preceding 5 years) received a 0.5mL dose of Flucelvax Quadrivalent vaccine, intra-muscularly, at Day 0.

Biological: Flucelvax Quadrivalent vaccine

Interventions

Flublok Quadrivalent vaccine BIOLOGICAL

Pharmaceutical form: Suspension for injection Route of administration: Intramuscular

Frequently vaccinated Group 1: QIV-R; Infrequently vaccinated Group 4: QIV-R

Fluarix Quadrivalent vaccine BIOLOGICAL

Pharmaceutical form: Suspension for injection Route of administration: Intramuscular

Frequently vaccinated Group 2: QIV-E; Infrequently vaccinated Group 5: QIV-E

Flucelvax Quadrivalent vaccine BIOLOGICAL

Pharmaceutical form: Suspension for injection Route of administration: Intramuscular

Frequently vaccinated Group 3: QIV-C; Infrequently vaccinated Group 6: QIV-C

Eligibility Criteria

• Age: 21 Years - 49 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Able to provide informed consent
• Willing and able to provide 4 blood samples at D0, 14, 150 and 330 post-vaccination
• Has not received influenza vaccine for at least 6 months
• Willing to provide current mobile phone number for SMS reminders

You may not qualify if:

• Known contraindication(s) for QIV (e.g. hypersensitivity to vaccine component (including eggs)).
• Recently (last 7 days) or currently ill or has a fever above 38 degrees celsius
• Cannot recall if they were vaccinated against influenza during more or less than two of the preceding five years. Vaccinated during two of the preceding five years.
• Hypogammaglobulinaemia on immunoglobulin replacement
• Undergoing immunosuppressive therapies including corticosteroids

Sponsors & Collaborators

• Tan Tock Seng Hospital: lead
• A*Star: collaborator
• University of Melbourne: collaborator
• Sanofi: collaborator

Study Sites (1)

National Centre for Infectious Diseases (NCID)

Singapore, Singapore, 308442, Singapore

Location

Related Publications (2)

• Gouma S, Zost SJ, Parkhouse K, Branche A, Topham DJ, Cobey S, Hensley SE. Comparison of Human H3N2 Antibody Responses Elicited by Egg-Based, Cell-Based, and Recombinant Protein-Based Influenza Vaccines During the 2017-2018 Season. Clin Infect Dis. 2020 Sep 12;71(6):1447-1453. doi: 10.1093/cid/ciz996.

  PMID: 31598646 BACKGROUND

• Wang W, Alvarado-Facundo E, Vassell R, Collins L, Colombo RE, Ganesan A, Geaney C, Hrncir D, Lalani T, Markelz AE, Maves RC, McClenathan B, Mende K, Richard SA, Schofield C, Seshadri S, Spooner C, Utz GC, Warkentien TE, Levine M, Coles CL, Burgess TH, Eichelberger M, Weiss CD. Comparison of A(H3N2) Neutralizing Antibody Responses Elicited by 2018-2019 Season Quadrivalent Influenza Vaccines Derived from Eggs, Cells, and Recombinant Hemagglutinin. Clin Infect Dis. 2021 Dec 6;73(11):e4312-e4320. doi: 10.1093/cid/ciaa1352.

  PMID: 32898271 BACKGROUND

MeSH Terms

Conditions

Influenza, Human

Condition Hierarchy (Ancestors)

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

Study Officials

• Barnaby Young, Dr

  National Centre for Infectious Diseases

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator, Head of Singapore Infectious Disease Clinical Research Network

Study Record Dates

• First Submitted: July 12, 2022
• First Posted: July 29, 2022
• Study Start: September 29, 2022
• Primary Completion: April 14, 2023
• Study Completion: February 6, 2024
• Last Updated: October 31, 2025

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: After study publication.
• Access Criteria: All researchers.

Locations

SG (1)