Inno4Vac proposes an ambitious programme that will harness the latest advances in immunology, disease modelling, and modelling for tackling persistent scientific bottlenecks in vaccine development and for de-risking and accelerating this process. To reach this aim the project is divided into four interlinked subtopics. In Subtopic 1, artificial intelligence in combination with big data analysis and computational modelling will be used to build an open-access and cloud-based platform for in silico vaccine efficacy assessment and development. Subtopic 2 will develop new and improved controlled human infection models (CHIM) against influenza, RSV and C. difficile that will enable early vaccine efficacy evaluation. Subtopic 3 will contribute to the development of cell-based human in vitro 3D models that resemble the in vivo situation of an infection at the mucosa and more reliably predict immune protection. These models will be combined with the development of related functional immune assays for clinically relevant (surrogate) endpoints. Finally, Subtopic 4 will develop a modular one-stop computational platform for in silico modelling of vaccine bio-manufacturing and stability testing. In parallel to the scientific-technical work, the partners will develop strategies and roadmaps for positioning the newly developed models in the regulatory framework and integrating them into pharmaceutical vaccine development. The overall workplan is underpinned by horizontal activities on coordination/management and dissemination/communication, including data management and future sustainability. To achieve these ambitious objectives, Inno4Vacc has assembled a multidisciplinary consortium from academic and research institutions, industries, regulatory bodies, and vaccine R&D alliances. This unique partnership brings together clinical, immunological, microbiological, systems biology, mathematical models, and regulatory expertise and includes world-leaders in each respective field.

Despite the availability of flu vaccines for decades, influenza is still an important disease in both developing and developed countries with 500,000 casualties annually and many more people affected. From a global health perspective, the lack of effectivity, availability, affordability and accessibility of flu vaccines significantly limits our ability to respond to the seasonal flu every year and in the event of a pandemic. Currently, a low vaccine effectivity of 40% implies that 60% of vaccinated people are not sufficiently protected, with low confidence further contributing to limited uptake/immunization. In this project, public and private R&D organizations in India, EU and US collaborate on the development of two novel influenza vaccine concepts that meet the requirements of global vaccination, aiming to achieve <10% instead of 60% non-responders, lower costs, and better accessibility. The first approach combines a low dose of a commercial, inactivated, seasonal flu vaccine with a novel, potent adjuvant, and will deliver proof-of-concept in Phase I and IIa trials within 5 years. The second approach builds on three innovations: 1) a novel recombinant HA with increased immunogenicity, 2) a potent adjuvant, and 3) an easy, needle-free delivery by intradermal patches. Contra-productive parts of HA will be removed to increase the immunogenicity of neutralizing epitopes. The adjuvant further stimulates protective immunity and immunological memory. The use of intradermal patches opens possibilities for self-administration, which will improve vaccine uptake in developing as well as developed countries. With proven nonclinical immunogenicity and safety, we will embark on clinical development of this concept after completion of the project. These plans differ in complexity and timelines but are realistic with chances to deliver next-generation flu vaccines for the globe.