PolyVax: A Novel Polymeric Nanoparticles Platform for Smart mRNA Vaccination
Seminar abstract: Vaccination has been one of the main successes of modern society, remarkably improving the human beings’ half-life thanks to the eradication of many infectious diseases. Traditional vaccines were composed of entire or fractions of the infectious agent. However, they account with unsolvable disadvantages, such as safety issues and low immunogenic potential that requires the addition of adjuvants.
In this context, the use of mRNA for immunizing purposes has shown an enhanced performance, as demonstrated by the very fast approval of two mRNA vaccines preventing SARS-CoV-2 infection. Beyond success in preventing viral infection, mRNA has also spread the use of vaccination for therapeutic cancer applications, and currently, the bibliography demonstrating research studies using mRNA therapeutic vaccines is huge. Nevertheless, the tech transfer is still limited. In this context, our project aims to build up a mRNA vaccination platform by the development of a mRNA vaccine based on proprietary polymeric nanoparticles, with demonstrated safety, efficacy and selectivity to target dendritic cells.
Based on our experience on biomaterials engineering, we developed a library of oligopeptide-end modified poly (beta aminoesters) (OM-pBAE) by two-step Michael addition of primary amines to acrylates, followed by oligopeptides end capping. In parallel, we have also set up the methodology for the in vitro transcribed mRNA synthesis, what enables the synthesis of different mRNAs encoding for different reporter genes, for the proof-of-concept studies, as well as for pathogenic microorganisms’ antigens and tumor associated antigens to broad the cohort of patients to be treated. The proprietary OM-pBAE demonstrated high efficiency on the encapsulation of various mRNA, by electrostatic interaction between the cationic polymers and the anionic nucleic acid, for the formation of small nanometric (<180nm) particles, able to be freeze-died without losing their integrity and functionality for, at least, 9 months. By the selection of the appropriate oligopeptide composition, we found a formulation that selectively targets dendritic cells after parenteral administration.
In addition, this formulation is able to promote dendritic cells maturation in vitro and in vivo and to generate a specific immune response against encoded model antigens in mice. In conclusion, we have been able to design a platform for the production of mRNA vaccines based on polymeric nanoparticles able to overcome the main limitations that traditional vaccines present. Our platform represents a turning point in the era of vaccination for infectious diseases prophylaxis and tumor therapies.
Cristina Fornaguera is an associate professor of Institut Químic de Sarrià (IQS), from Ramon Llull University, since September 2018.
She obtained her BSc in Biotechnology, specializing in Biomedicine, from the Autonomous University of Barcelona and PhD in Development and control of medicines with honors, cum laude and awarded with the Extraordinary Thesis Award of the University of Barcelona during the 2014-2015 academic year. The main aim of her thesis was the preparation and characterization of polymeric nanoparticles to cross the blood-brain barrier.
During this period and thanks to the multidisciplinary character of her PhD, she started acquiring expertise in colloidal chemistry, nanomedicine, biotechnology, pharmaceutical technology, advanced delivery systems formulation and characterization, in vitro studies of safety and efficacy of nanosystems, and in vivo experimentation to test the designed compounds. She is now consolidating her experience in all these research fields.
Her interest in nanomedicine led her to industrial research, specifically to Sagetis Biotech, where she worked as a postdoctoral fellow from 2015 to 2018, on the design of innovative polymeric nanosystems capable of overcoming a fundamental engineering challenge: the development of safe and effective delivery vectors for currently unmet medical needs. Simultaneously, she developed an academic career as a tutor and docent in the IQS; work that continues currently with her recent position as associate lecturer and researcher at IQS. Her research interests are focused on nanomedicine, biomaterials, bioengineering and drug delivery systems for immunotherapeutic applications.
Her main research focus is on designing novel vaccination strategies. She has presented her research results at national and international conferences, authored many original research publications and review papers,co-edited a special issue and collaborated as a reviewer for many peer-reviewed journals. She has also achieved funding in competitive calls. To remark, the funding of the CoviNanoVax project, that she leads, for the development of one of the Spanish vaccines to prevent Covid-19 infection.