Understanding the mode of action of vaccine adjuvants for mechanistically informed ‘intelligent’ vaccine design

• Applicant: Dr. Sören Reinke
• Subject Area: Immunology
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 495054088

The current SARS-CoV-2 pandemic strikingly underlines the need for efficacious vaccines to protect the human population from life-threatening diseases. In addition to new emerging pathogens, other complex diseases such as AIDS, tuberculosis, or malaria have high mortality rates and severely burden health care systems worldwide. Therefore, the development of efficacious vaccines is of extremely high relevance to save lives and improve health. Current vaccines employ various platforms such as inactivated or live-attenuated pathogen, subunit (protein) vaccines or the recently emerged viral vectored and mRNA technologies. Since protein antigens alone are poorly immunogenic, protein-based vaccines usually require an adjuvant to enhance immunogenicity and thereby increase efficacy. Adjuvants, such as mineral salts, emulsions, saponins, or liposomes can be added to subunit vaccines to shape the immune response quantitatively and qualitatively. Ideally, the adjuvant should specifically induce the appropriate immune response that is required to neutralise the targeted pathogen. Therefore, understanding the mode of action (MoA) of vaccine adjuvants is essential for the development of efficacious protein vaccines. Two prominent types of vaccine adjuvants that have been shown to promote robust immune responses as part of different human vaccines are oil in water emulsions and liposome-based adjuvants. Nevertheless, there is a huge gap in our detailed understanding of the mechanism of these adjuvants, in particular how the innate activation leads to specific adaptive immune responses, which would enable mechanistically informed vaccine design. Furthermore, the most advanced adjuvants, such as MF59 and AS01, are patented by pharmaceutical companies and not available to vaccine researchers, thereby considerably limiting development of vaccines for the low-income countries where efficacious and low-cost vaccines are greatly needed.My host lab (The Jenner Institute, Oxford, UK) is working in a close partnership with the Vaccine Formulation Institute (VFI) in Geneva, Switzerland, the only open-source adjuvant developer for clinical applications. With support from the Bill and Melinda Gates Foundation, VFI are developing, and characterising novel adjuvants aimed for clinical application and supply for global use on an open-access basis. The project proposed here will perform an in-depth spatio-temporal analysis of the MoA of different emulsion and liposome-based adjuvants using murine in vivo and in vitro models. The goal is to gain a deeper understanding of the MoA of adjuvants, a key step towards an improved vaccine design, which could accelerate the development of efficacious vaccines against fatal diseases. For this purpose, we are aiming to i) characterise the humoral response to an adjuvanted malaria vaccine, ii) describe the spatio-temporal innate response to the adjuvants, and iii) assess the role of the inflammasome in the MoA of the adjuvants.

• DFG Programme: WBP Fellowship
• International Connection: United Kingdom
• Host: Dr. Anita Milicic