In a nutshell

ENDFLU will develop three complementary next-generation influenza vaccination strategies for the world, fueled by the unique combined expertise of Indian and European partners in rational vaccine design and development.

In summary, the project will address the following objectives:

  • Create a repository of pre-pandemic GMP-compliant MVA-based vaccine seeds, each encoding an influenza hemagglutinin (HA), based on European partners' demonstration of clinical safety and cross-clade immunogenicity of MVA-H5.
  • Optimize and select protein- and MVA-based constructs developed by Indian and European ENDFLU partners, resulting in a rationally combined vaccine formulation that induces broadly protective humoral and cell-mediated immunity against all influenza manifestations. This will be advanced in a Phase I clinical trial and Controlled Human Infection Model (CHIM) study.
  • Pre-clinically advance other promising protein- and MVA-based constructs toward future development beyond ENDFLU.

ENDFLU will run its activities in parallel along two main development tracks: axis 1 and 2.

Development along 2 main axes

A repository of (pandemic) seed vaccine candidates will be established based on the expression of influenza hemagglutinin (HA) by the Modified Vaccinia Ankara (MVA) vector.

This is a technologically- and clinically-advanced platform developed by ENDFLU partners, with demonstrated broad intra-subtypic protective efficacy against influenza, elicited by humoral and cell-mediated immunity, both in animal models and in humans. Good Manufacturing Practice (GMP)-compliant seed vaccine candidates based on the MVA vector expressing influenza HAs will be produced for a pandemic preparedness vaccine candidate repository. The regulatory path towards their use upon the emergence of a new influenza pandemic will be established, in consultation with industry and regulatory authorities in EU (EMA) and India (CDSCO).

Axis 1
Axis 2

Pre-clinically well-advanced vaccine candidates will be optimized, by leveraging unique European and Indian scientific progress, strong expertise and know-how in the development of next-generation influenza vaccines.

These include protein-based constructs based on a range of target influenza proteins and parts thereof as well as MVA constructs with conserved and/or cellular immunity targets. These ENDFLU vaccine candidates and other promising leads will be further pre-clinically advanced throughout the duration of the project. Those reaching rigorous and critical milestones for their eventual production under Good Laboratory Practice (GLP) conditions will be selected to enter GMP production and Phase I clinical studies. One protein-based vaccine candidate and one MVA-delivered vaccine candidate will be selected based on preclinical stability, safety, immunogenicity and protective efficacy data as well as criteria facilitating their rapid, economical, large-scale production and distribution worldwide, including in low- and middle-income countries (LMICs).

Clinical development

The protein-based vaccine candidate will be tested for safety and immunogenicity in a Phase I dose escalation clinical trial in India. The dose that demonstrates the highest safety and immunogenicity profile will subsequently be combined with the MVA-delivered vaccine candidate as a single MVA-protein formulation to assess its safety and immunogenicity in a Phase I clinical trial, and subsequently to validate its protective efficacy in a CHIM study in the EU.


This approach takes advantage of promising influenza and unique vaccine development strategies of the Indian and European partners to ensure the synergistic development of a next generation rationally-designed influenza vaccine candidate that will induce broad and potent humoral immunity against seasonal influenza A and B viruses through the protein-based component and robust and cross-reactive cell-mediated immunity through the MVA-based component.


Finally, a detailed exploitation plan, including a clinical development roadmap, will be prepared for continued clinical development of ENDFLU’s broadly protective influenza vaccine beyond the ENDFLU Phase I clinical trial.

The ENDFLU project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No. 874650.