Next-generation flu vaccines for the world
Despite decades of vaccination programmes, influenza continues to cause around half a million deaths every year worldwide. Seasonal vaccines often provide only moderate protection, particularly in older adults, while their cost and availability remain major barriers in many low- and middle-income countries. The EU-funded INDIGO(opens in new window) project set out to address these challenges by developing next-generation influenza vaccines that are more effective, affordable and accessible. One of the key goals was to also strengthen preparedness for future pandemics.
Complementary strategies for better vaccines
The project pursued two innovative vaccine concepts designed to meet different needs. The first focused on improving seasonal influenza vaccination by combining a greatly reduced dose of a commercially available vaccine with LiteVax Adjuvant(opens in new window) (LVA), a novel synthetic adjuvant developed to enhance immune responses. The second aimed to improve preparedness for future influenza pandemics through redesigned viral antigens, next-generation adjuvants and needle-free intradermal delivery. “INDIGO combined several complementary innovations, aiming to develop vaccines that provide stronger protection while making vaccination more affordable and easier to deliver,” explains project coordinator Elly Van Riet. LVA emerged as one of the project’s most promising innovations. The fully synthetic adjuvant can be manufactured at low cost, does not rely on scarce raw materials and has demonstrated long-term stability for at least five years. Most importantly, it showed the ability to substantially enhance immune responses while reducing the amount of vaccine antigen required.
Improved immune responses
Clinical studies conducted in Europe demonstrated that combining LVA with only one fifth of the standard influenza vaccine dose generated immune responses(opens in new window) comparable to those produced by a full-dose commercial vaccine without an adjuvant. “Replacing much of the vaccine antigen with the inexpensive adjuvant creates the opportunity to develop a lower-cost vaccine without compromising immune protection,” states Van Riet. In older adults, who often respond less effectively to influenza vaccination, the team observed improved immune responses that approached those typically seen in younger individuals. Researchers also explored the biological mechanisms(opens in new window) responsible for these effects using advanced multi-omics technologies. The analyses revealed enhanced interferon signalling, improved antigen presentation by dendritic cells and stronger activation of CD4+ T cells, providing valuable insights into how the adjuvant strengthens protective immunity.
Building global preparedness
Beyond scientific advances, INDIGO brought together partners from Europe, India and the United States. The consortium established the foundations for clinical development in India, including harmonised manufacturing, regulatory procedures and laboratory testing. It also examined how innovative vaccines could improve global access once they reach the market, developing legal and regulatory recommendations for the EU and India to support wider vaccine availability in low- and middle-income countries. Social science research in India(opens in new window) and the Netherlands(opens in new window) further showed that vaccine uptake depends not only on risk perception but also on affordability and local accessibility, with intradermal patch technologies offering particular promise for reducing costs in resource-limited settings. “Our greatest achievement has been building a truly transdisciplinary partnership capable of translating laboratory discoveries into clinical development,” highlights Van Riet. The European component of the project has now concluded, while clinical development continues in India. The technologies developed by INDIGO could support larger-scale vaccine manufacturing, facilitate broader access to affordable influenza vaccines worldwide and strengthen global preparedness against future pandemic threats.
