Each year, general practitioners, hospitals and ICUs are overwhelmed with influenza patients. This viral infection is highly contagious, mainly affects the respiratory system, and can affect everyone. Seasonal influenza outbreaks vary in severity every season. The most recent severe season was in 2017-2018 which resulted in approximately 80,000 deaths in the US alone and another 152,000 in Europe. In addition to these seasonal outbreaks, global pandemics can also hit the population. Perhaps, the most famous one is the Spanish flu that emerged in 1918 and was responsible for the death of millions.
The focus of influenza treatment is prevention rather than curation. This is done by yearly vaccination of at-risk populations such as the elderly. Unfortunately, the protective effects of influenza vaccines are limited in the elderly due to senescence of their immune system. Moreover, the constant evolution of viral strains limits the effectiveness of seasonal influenza vaccines (i.e. the effectiveness varies from 15 to 60% every year). Once patients become ill due to influenza, they can be treated with small molecule antiviral drugs. However, drug-resistant influenza viruses frequently emerge and these may spread quickly in the population, adding complexity to the problem.
The main goal of this project is to come up with a radically different approach to control influenza. Our aim is to create biologicals that will be applied locally to treat and/or prevent influenza. The team will focus on the following specific goals:
- Development of a pan-influenza A neutralizing biological that will be effective against all influenza A strains and can be used every season and during global outbreaks.
- Generation of a stable cell line to produce the anti-influenza biologicals compliant with industrial production guidelines.
- Creation of a formulation that allows nebulization and hence local delivery of the biological in the airways.
- Execution of a cost-effectiveness study of the proposed biological-based solution with a focus on the prophylactic treatment in the elderly.
Facts & Figures
Pathogen epidemics will be controlled; new molecular insights are translated to health and prevention policies
Contribution to the project
The Lab of Prof. Xavier Saelens from the VIB-UGent Center for Medical Biotechnology together with the lab of Prof. Jan Steyaert from the VIB-VUB Center for Structural Biology will start by generating pan-influenza A biologicals. Two biologicals will be combined by the lab of Prof. Xavier Saelens to come up with a bispecific lead that will be validated in vitro and in vivo. The antiviral potency of the new biological will also be tested in vitro against viruses that are isolated from critically ill influenza patients by the group of Dr. Marijke Reynders.
The optimized biological lead product will be stably expressed in a CHO cell line that will be developed by the group of Prof. Nico Callewaert from the VIB-UGent Center for Medical Biotechnology. Moreover, a GMP-compliant production and purification process will be developed to comply with pharmaceutical production grade guidelines by Eurofins. The nebulization of the biological will be optimized by the group of Prof. Nathalie Heuzé-Vourc’h. Finally, in vivo nebulization and the protective potential of the biological against a candidate pandemic influenza virus strain will be tested and validated by RIVM in the Netherlands.
Throughout the duration of the project, the cost effectiveness of the proposed treatment will be evaluated by the group of Prof. Dominique Van Dijck at the UGent.
This consortium aims to develop a CHO cell line that complies with large scale production guidelines, will have FTO status, and will also make it freely available for the research community without imposing restrictions. This strongly contributes to the open science policy of VIB in general.
In addition, the consortium will develop a biological with pan anti-influenza A activity that will be ready for clinical development. The formulation of this biological stabilizes it during nebulization. This allows for a focal treatment locally, namely at the infection site, thereby reducing dosing and costs of therapy.
Finally, the team will determine the cost-effective of the anti-influenza biological, weighing the societal benefits against the estimated cost of the new drug.
Upon successful completion of the project, a technology platform for the expression of antimicrobial biologicals in a biopharmaceutical production compliant cell line will have been developed. Importantly, nebulization of biologicals will also be developed during this project which reduces costs of therapy and will a pave the way to treat disease caused by other lung pathogens such as Mycobacterium tuberculosis, Pseudomonas aeruginosa and Acinetobacter baumanii.
Prof. Xavier Saelens emphasizes why nanobody therapies can help to protect our society against influenza: “While it takes 2-3 weeks before influenza vaccines protect, a nanobody-based prophylaxis would offer immediate protection. In addition, we are determined to use nanobodies that protect against multiple influenza A virus subtypes, including future pandemic strains."