Periodic Reporting for period 1 - QS21-Mech (Target identification and elucidation of the molecular mechanism of action of saponin vaccine adjuvants QS-21 (QS21Mech))
Reporting period: 2020-03-01 to 2022-02-28
- This novel research represents a unique opportunity to address long-standing mechanistic questions concerning saponin immunopotentiation that have not been resolved so far. The unprecedented identification of the involved receptor proposed herein will allow us to determine for the first time the mechanism of action of QS21. This combined knowledge will, in turn, give us the opportunity to rationally design saponin adjuvants with the highest potency for each individual antigen (depending on the different pathways the antigen is being processed by the immune system), resulting in new and more effective subunit vaccine for the benefit of the society.
- The overall objective of this original proposal is to elucidate the mechanism of action by which the saponin adjuvant QS-21 potentiates the immune response. To achieve this ambitious but feasible goal, three main objectives have been proposed:
1: Synthesis of a variety of novel saponin photoaffinity probes (SPAPs), consisting of QS-21 derivatives as bioactive ligands, linked to a photoreactive group (benzophenones, and diazirines) and biotin as a reporter group.
2: Identification of the saponin lead compound in terms of a) best adjuvant activity/immunological response in mice, and b) selective capture of the putative target by the SPAPs via the photoreactive group.
3: Identification of involved molecular target via in vitro studies with murine DCs, followed by chemical proteomic analysis.
Dissemination. Since all the WPs of “QS21Mech” have not been fully completed due to complicated and long synthetic route and additionally COVID19 pandemic, the dissemination of the final scientific results will be presented in appropriate international conferences to be held either by the end of 2022 or early 2023. In the meantime, I have communicated some of our preliminary results in a Summer School in Biomedical Glycoscience, Venue: Jaca (Huesca, Spain). Dates: 8th-10th June 2022, Organized by the Carbohydrates Group of the Spanish Royal Society of Chemistry, through a poster presentation. Moreover, I have attended the “3rd Glycobasque Meeting” held in CIC bioGUNE, (Derio, Bizkaia), on March 12nd-13th, 2020 and had the opportunity with well-known scientist to share the idea of “QS21Mech”. Since I am still working on the project thanks to Prof Fernandez Tejada’s lab funds for an additional year, we are optimistic about finalizing “QS21Mech”. The high value of the results will be disclosed in scientific journals of the highest impact (Open Access according to EC policy), such as Nature, Science, Nature Chem, Nat Chem Biol, J Am Chem Soc or Angew Chem Int Ed. I am expecting to publish in a high-impact, peer-reviewed journals, although care will be taken to not jeopardize possible exploitation of results due to the translational aspect of our project. Once we will have final conclusion of the project, I will use the available tools from the European Commission (http://horizon-magazine.eu/) to publish some short articles or online news headlines (http://cordis.europa.eu/wire) based on our achievements. I have already used the platform Junior Research Seminar Series in 2022, Jan 9 from CIC bioGUNE’s strategies of dissemination where I share the advances of this project with my colleagues.
Exploitation and IPR issues. The outcomes of the proposed research i.e. the identification of receptors of saponin adjuvants are capable of ultimately leading to novel, tailored saponin adjuvants that can be exploited by the pharmaceutical industry in the development of novel vaccines to effectively combat diseases of a world-wide significance including cancer, tuberculosis, HIV, malaria and Ebola. There are different pharmaceutical companies that already use adjuvant systems containing QS-21 in various vaccines in all three stages of clinical trials and will be interested in the results of QS21Mech. In fact, Prof. Fernández-Tejada has had the opportunity to establish initial contacts with both companies on a basic level, and has established a solid relationship with an additional biopharma company as a collaboration partner. In addition, CIC bioGUNE Technology Transfer Manager, has broad experience in the translation of results from academia to companies and will fully support me along the project implementation once it is finalized.