Colorized scanning electron micrograph of a cell infected with the Omicron strain of SARS-CoV-2 virus particles (red). Image taken at the NIAID Integrated Research Facility at Fort Detrick, Maryland. Credit: NIAID, licensed under CC BY 2.0. /Wikimedia.
A typical COVID-19 vaccine presents a fragment of the SARS-CoV-2 spike protein to the body, allowing the immune system to recognize the virus and mount protection. However, emerging variants are increasingly evading this immune response through mutations in the receptor binding domain (RBD), threatening the effectiveness of existing vaccines.
This challenge has prompted research into new vaccines that target conserved regions of the RBD common to all SARS-like betacoronaviruses. Recent advances in the development of new broad-spectrum vaccines based on the Mosaic-8b nanoparticle candidate aim to provide cross-reactive immunity against known and future sarbecovirus strains and significantly enhance pandemic preparedness.
Search for pan-sarbecovirus solutions
The global fight against coronavirus disease (COVID-19) has highlighted the urgent need for effective vaccines to control the virus and protect public health. Since January 2020, there have been more than 7 million deaths worldwide,1 and that number continues to rise every day, but with the arrival of COVID-19 vaccines, the risk of death has decreased by 57 percent. I did 2. It is an RNA virus, which means it can mutate rapidly, 3 leading to the emergence of new variants that are highly transmissible. By expressing new antigenic epitopes that are not easily recognized by existing antibodies, the variants bypass the basic immunology behind most current vaccines and prevent the viruses from binding with the same affinity. There is a fear. For example, substitutions in the SARS-2 spike protein RBD in Omicron variants reduce the effectiveness of both vaccines and therapeutic monoclonal antibodies, 4 and lead to breakthrough infection in individuals regardless of their initial immunity to the virus. I did. 5 As a result, vaccines currently in circulation may not be effective in providing long-term protection against the virus as the virus continues to evolve. 6 Developing and distributing reliable vaccines that can induce effective neutralizing antibodies against new variants will help maintain immunity, prevent severe disease, and protect against future epidemics. This is extremely important. .
Developing variant-specific boosters is one possible approach, but producing a vaccine, or simply updating an existing one, can take months or years and requires significant financial investment. It is necessary. The severity of the coronavirus pandemic has been reinforced by a £240m investment from the UK Government to scale up vaccine production, effectively speeding up this process for the first initial vaccines. I meant it. 7 This means that, fortunately, researchers have been able to develop and test it. While distributing first doses in record time, constantly updating boosters to keep up with new viruses is costly and impractical. A better solution would be a universal vaccine that provides protection against both emerging sarbecoviruses and current SARS-CoV-2 variants without the need for ongoing adjustments.
Promising protection against SARS-CoV-2
With this in mind, the engineering biology CRDMO Ingenza, in partnership with the California Institute of Technology (Caltech), the University of Oxford, and the Center for Process Innovation (CPI), has partnered with the California Institute of Technology (Caltech), the University of Oxford, and the Center for Process Innovation (CPI) to develop We quickly prepared a suitable vaccine. Strains and variants. The principle behind the project, discovered by Professor Pamela J. The goal is to induce an immune response in the preserved part. Ingenza takes the lead in transferring vaccine candidate production from mammalian cells and E. coli to alternative microbial platforms, specifically Pichia pastoris and Bacillus subtilis, to reduce development time and costs while establishing a scalable manufacturing process I did. The company leverages its proprietary inGenius platform, designed to increase the efficiency and predictability of bioprocess development, to develop manufacturing microbial strains, scalable bioprocesses, and in-process controls, release assays, and drug substance We created the analytical methods necessary for characterization.
The resulting vaccine candidates include RBDs from SARS-CoV-2 and seven other coronaviruses that form so-called “mosaic 8b” nanoparticles. Therefore, these conserved regions should be present and unchanged in both undiscovered sarbecoviruses and novel variants of SARS-CoV-2 that may emerge in the future. A study published in 2022 showed that these Mosaic 8b nanoparticles were found to contain betacoronaviruses like SARS, which match the components present on the nanoparticles, as well as other related viruses not shown in the Mosaic 8b design. It was confirmed that it induces a protective immune response against. 8 These include SARS. Like betacoronaviruses found in animals, they may infect humans in the future.
Based on existing vaccine immunity
Further preclinical studies demonstrated the efficacy of the Mosaic 8b vaccine in inducing an immune response following prior vaccination or exposure to SARS-CoV-2. This is an important factor given that a large proportion of the population has likely encountered the virus by now. 9Mosaic 8b Nanoparticles are novel, broadly cross-reactive drugs that target multiple sarbecoviruses, including sarbecoviruses that are more closely related to SARS-CoV-2, with recall antibodies enhanced by previous immune responses. We were able to generate both antibodies. These antibodies showed superior ability to recognize different virus strains compared to homotypic nanoparticles in a mixture. Remarkably, antibodies generated by these nanoparticles also showed stronger avidity and neutralizing activity than antibodies induced by conventional homologous SARS-CoV-2 vaccines.
Additionally, this study provided valuable insight into the phenomenon of original antigenic guilt (OAS), in which the immune system tends to rely on memory cells from the initial exposure when faced with relevant antigens. 9 This vaccine can address some of the challenges associated with OAS. By generating new antibodies that target different sarbecovirus RBDs, rather than simply augmenting the production of existing antibodies specific to a particular SARS-CoV-2 strain. Overall, these findings demonstrate that a single dose of this vaccine elicits a broader protective immune response in immunologically naïve individuals compared to a single dose of the standard SARS-CoV-2 homologous vaccine. This suggests that it may cause. This indicates that Mosaic 8b may be able to provide broader and longer-lasting protection against different evolving SARS-CoV-2 strains and other sarbecoviruses.
conclusion
Although the Mosaic 8b vaccine is still in its early stages of development, it shows promise as a broad and cross-reactive immunization strategy that can provide comprehensive protection against existing and emerging sarbecoviruses. The project also serves as a template for developing vaccines that are future-proof against variant outbreaks, reducing the need for frequent iterations and updates. It has a multifaceted defense system that is resistant to virus escape, giving you greater protection against a variety of virus strains now and in the future.
Author biography
Dr. Leonardo Magneschi is Ingenza’s Vice President of Research and Technology Development. He has over 15 years of experience in microbiology and genetic engineering, holds a PhD in plant and microbial biotechnology, has published 17 papers in peer-reviewed scientific journals, and is an inventor on several international patents. We have a track record of He joined Ingenza in 2016 and has since been directly involved in customer projects for a wide range of applications, from pharmaceuticals and biofuels to renewable materials.
References
World Health Organization. (2024). WHO’s new coronavirus dashboard. https://data.who.int/dashboards/covid19/deaths World Health Organization. (2024). Coronavirus vaccinations have saved more than 1.4 million lives in the WHO European Region, a new study has found. https://www.who.int/europe/news/item/16-01-2024-covid-19-vaccinations-have-saved-more-than-1.4million-lives-in-the-who-european-region A new study found Sanjuán, R., Domingo-Calap, P. (2016). Mechanism of viral mutation. Cellular and Molecular Life Sciences: CMLS, 73(23), 4433-4448. https://doi.org/10.1007/s00018-016-2299-6 Willett, B. J., Grove, J., MacLean, O. A., et al. (2022). SARS-CoV-2 omicrons are immune evasion mutants with altered cell entry routes. Nature Microbiology, 7, 1161-1179. https://doi.org/10.1038/s41564-022-01143-7 Bergwerk, M., Gonen, T., Lustig, Y., et al. (2021). Breakthrough of COVID-19 infection among vaccinated healthcare workers. New England Medical Journal, 385(16), 1474-1484. https://doi.org/10.1056/NEJMoa2109072 Beukenhorst, A. L., Koch, C. M., Hadjichrysanthou, C., et al. (2023). SARS-CoV-2 induces non-sterile immunity and evades vaccine-induced immunity: implications for future vaccination strategies. European Journal of Epidemiology, 38(3), 237-242. https://doi.org/10.1007/s10654-023-00965-x British Parliament. (2021). Manufacture of COVID-19 vaccine. https://post.parliament.uk/manufacturing-covid-19-vaccines/ Cohen, A.A., van Doremalen, N., Greaney, A.J., et al. (2022). Mosaic RBD nanoparticles protect against attack by various sarbecoviruses in animal models. Science, 377(6606), eabq0839. Cohen, A.A., Keeffe, J.R., Schiepers, A., et al. (2024). Mosaic sarbecovirus nanoparticles induce cross-reactive responses in vaccinated animals. Cell (published online ahead of print), 187, 1-18. https://doi.org/10.1016/j.cell.2024.07.052 Filed Under: Infectious diseases
Tags: betacoronavirus immunity, cross-reactive vaccines, microbial manufacturing platform, original antigenic sin, receptor binding domain, SARS-CoV-2 variants, vaccine development
