The next-generation live-attenuated vaccine, named OTS-228, has demonstrated significant safety and efficacy in pre-clinical studies, marking a hopeful advancement in the fight against COVID-19. Developed by researchers from the Friedrich-Loeffler-Institute on the Isle of Riems, the Institute of Virology and Immunology (IVI) Bern, and the University of Bern, Switzerland, in collaboration with the Swiss biotech company Rocketvax AG a subsidiary of Swiss Rockets AG, this next-generation vaccine aims to provide enhanced protection against emerging SARS-CoV-2 variants and reduce transmission.
The COVID-19 pandemic, which has been responsible for around 7 million deaths worldwide, necessitates continuous innovation in vaccine development. Despite the significant success of the existing vaccines against COVID-19, there remains an urgent need for improved vaccines that can offer broader immunity against emerging virus variants and reduce ongoing transmission. To this end, the scientists genetically weakened the SARS-CoV-2 virus using the so-called "One-to-Stop (OTS)" strategy in such a way that the virus was significantly attenuated, resulting in the promising vaccine candidate OTS-228. Administered intranasally to both golden Syrian hamsters and K18-hACE2 mice, OTS-228 showed promising safety and efficacy. It is particularly noteworthy that the live-attenuated vaccine was not transferred to contact animals, and all animals developed a broad and strong immune response against SARS-CoV-2.
Key findings from the pre-clinical studies include:
- Broad Variant Protection: Vaccinated animals remained disease-free when exposed to both the wild-type SARS-CoV-2 and newer variants such as Omicron BA.2, BA.5, and XBB1.5.
- Transmission Prevention: The live-attenuated vaccine completely prevented virus transmission to unvaccinated contact animals for the wild-type SARS-CoV-2 and significantly reduced transmission for Omicron variants.
- Strong Immune Response: All vaccinated animals exhibited a local and mucosal immune response, in addition to the broad and strong serum immune response, indicating the vaccine’s potential to offer comprehensive protection.
With these results, the researchers are confident that they will be able to restrict the further spread of COVID-19. The scientists emphasize that the construct they have created can be adapted with very simple means and can therefore be used to react quickly to newly emerging SARS-CoV-2 variants. In addition, it is also possible to apply this method of attenuation to completely different, newly emerging and potentially pandemic viruses in order to produce valid, safe and effective live vaccine candidates.
OTS-228 is now being further developed by Rocketvax AG for the use in clinical trials.
Publication
Schön, J., Barut, G. T., Trüeb, B. S., Halwe, N. J., Berenguer Veiga, I., Kratzel, A., Ulrich, L., Kelly, J. N., Brügger, M., Wylezich, C., Taddeo, A., Moreira, E. A., Túrós, D., Grau-Roma, L., Ahrens, A. K., Schlottau, K., Britzke, T., Breithaupt, A., Corleis, B., et al. (2024). A safe, effective and adaptable live-attenuated SARS-CoV-2 vaccine to reduce disease and transmission using one-to-stop genome modifications. Nature Microbiology, in Press.
DOI: 10.1038/s41564-024-01755-1
