Intranasal, rapid-acting vaccine for all seasonal and pandemic influenza viruses

Project Information

FLUniversal

Grant agreement ID: 101080692

DOI

10.3030/101080692

EC signature date 8 May 2023

Start date 1 June 2023

End date 31 May 2027

Funded under

• Health

Total cost

€ 7 567 787,50

EU contribution

€ 7 567 787,50

Coordinated by

Zafiro Business Solutions Korlatolt Felelossegu Tarsasag
Hungary

Periodic Reporting for period 1 - FLUniversal (Intranasal, rapid-acting vaccine for all seasonal and pandemic influenza viruses)

Reporting period: 2023-06-01 to 2024-11-30

Summary of the context and overall objectives of the project

The FLUniversal Consortium is engaged in developing DeltaFLU, a universal influenza vaccine that can protect against all types of influenza viruses. DeltaFLU is made from specially weakened, non-replicating influenza virus strains that have been genetically modified to be safer and more effective. The goal is to provide broad protection by using DeltaFLU in a two-step vaccination process, helping the immune system target parts of the virus that do not change much across different strains. The vaccine will be given as a nasal spray, thereby inducing special antibodies to protect the nose and throat, which may also help stop the spread of the influenza virus.

During the project, the Consortium will develop a faster way to test new influenza vaccines by a safe, controlled method to simulate natural infection in humans. This new approach will speed up vaccine testing, provide valuable insights into how flu vaccines protect people, and help improve guidelines for vaccine development and approval.

The successful completion of the project will help reduce the impact of influenza and potentially other infectious diseases by developing a universal flu vaccine and improving vaccine production. It will also strengthen international collaboration, enabling faster and more effective responses to health emergencies and epidemics. The project will benefit citizens by lowering the risk of cross-border health threats, such as flu pandemics, and support the scientific community in understanding the influenza virus, its transmission, and its interaction with humans through a new controlled human infection model. The findings will be widely shared to enhance global knowledge and preparedness.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

Technological activities were conducted in work packages WP2, WP3, WP4, and WP5. Key completed activities include:

WP2 - Production of Vaccine and Challenge Strains
- Virus Seed Production & Testing: Pre-Master Virus Seeds for H3N2 and H7N9 were successfully produced and met required standards. H3N2 production was completed at DeltaFLU, and testing for both strains is in progress.
- Assay Development: Adventitious assays were conducted in both in vitro and in vivo formats for virus neutralization.
- Stability Testing & Virus Bank Release: Virus stability testing was completed, and virus banks were released to the CMO in France. Both strains showed high titers, with GMP production expected by Q1 2025.
- Challenges: Issues in virus neutralization were addressed, and a refined protocol is under development.

WP3 - Preclinical Evaluation
- Ferret Studies: Forty-two ferrets were prepared for studies with the H3N2 strain.
- Hamster Studies: Studies using the same H3N2 strain were conducted and concluded in November. Immune response and pathology analysis are ongoing.
- Toxicology and Trivalent Vaccine Studies: Study designs were prepared, and a trivalent vaccine study is planned.

WP4 - Clinical Evaluation
- Dose-Confirmation Study: A small study with 10 subjects was planned, with all documentation ready for ethics approval and submission. Execution is scheduled for late 2024/2025.
- Phase I Vaccination Study: The study was delayed due to pending GMP manufacturing.
- Phase II CHIM Vaccination-Challenge Study: This study was delayed for the same reason.

WP5 - Immunology and Correlates of Protection
- Preclinical immunological analysis of the first hamster study began, focusing on B and T cell responses.
- Coordination of reagents for clinical immunological analysis is ongoing, with priority discussions due to high reagent costs.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

The project aims to achieve four key wider impacts:

1. Reducing Infectious Disease Burden: Advance disease management by developing a universal influenza vaccine and improved vaccine manufacturing technologies.
2. Strengthening International Cooperation: Enhance global research and innovation expertise, sharing knowledge to combat infectious diseases and improve emergency preparedness for epidemics.
3. Benefiting Citizens: Mitigate health threats from epidemics, with a focus on reducing the impact of influenza outbreaks and pandemics.
4. Advancing Scientific Understanding: Deepen knowledge of influenza virus biology, transmission, and human interaction via a novel controlled human infection model, while promoting dissemination of project findings.

By the first reporting period (01/06/2023 - 30/11/2024), the Consortium generated vaccine viruses, completed stability testing, released primary virus banks to the CMO, and confirmed high-titre master virus seeds meeting all criteria for GMP vaccine production in Q1 next year. Preclinical studies were completed, and protection data support a clinical trial application, with immunogenicity studies ongoing. (Wider impact No1)

In alignment with Wider Impact 2, which emphasizes international cooperation, the consortium has actively engaged global experts and established collaborations with leading institutions to amplify the project's global influence. Key achievements include forming an extended Scientific Advisory Board featuring internationally recognized experts like Otfried Kistner, Christine Dahlke, Geert Leroux-Roels, and Catherine Luke, providing strategic guidance for the project.

Additionally, consortium representatives actively participated in key events like the CIVIC meeting and the World Vaccine Congress 2024, showcasing FLUNIVERSAL's objectives and advancements in CHIMs for vaccine development. These activities highlight the consortium's dedication to international collaboration and advancing infectious disease research.

Progress toward Wider Impacts 3 and 4 was limited until the end og 2024, as these outcomes depend on ongoing activities and require more time to fully develop, such as citizens benefiting from validated vaccines or new human infection models for influenza. However, some notable achievements were made during this period.