The global effort to combat COVID-19 has spurred the development of a novel vaccine candidate, the mosaic-8b nanoparticle, designed to offer broad protection against SARS-like betacoronaviruses. This innovative approach, spearheaded by researchers at the California Institute of Technology (Caltech), the University of Oxford, and Ingenza, aims to address the challenge of emerging variants evading current vaccine-induced immunity.
The mosaic-8b vaccine presents receptor-binding domains (RBDs) from SARS-CoV-2 and seven other coronaviruses in a nanoparticle format. This strategy directs the immune response toward conserved regions of the RBD, which are shared among sarbecoviruses. By targeting these conserved areas, the vaccine aims to provide cross-reactive immunity against both known and future SARS-CoV-2 variants, as well as other sarbecoviruses with the potential to jump to humans.
Addressing Viral Evolution
Traditional COVID-19 vaccines typically present fragments of the SARS-CoV-2 spike protein, enabling the immune system to recognize and defend against the virus. However, the rapid mutation rate of SARS-CoV-2, an RNA virus, leads to the emergence of variants with mutations in their RBDs. These mutations can reduce the effectiveness of existing vaccines, as the virus may no longer bind with the same affinity, leading to breakthrough infections. Developing variant-specific boosters is one approach, but it is costly and time-consuming. A universal vaccine that provides protection against emerging sarbecoviruses and current SARS-CoV-2 variants would be a more effective solution.
Ingenza's Role in Vaccine Development
Ingenza, an engineering biology CRDMO, has played a crucial role in formulating the mosaic-8b vaccine. The company led the transfer of 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. Ingenza harnessed its proprietary inGenius platform to create manufacturing microbial strains, scalable bioprocesses, and analytical methods required for in-process controls, release assays, and drug substance characterization.
Pre-clinical Evidence
Pre-clinical research has demonstrated the mosaic-8b vaccine's effectiveness in triggering an immune response following prior vaccination or exposure to SARS-CoV-2. The mosaic-8b nanoparticles were able to produce both recall antibodies – boosted from previous immune responses – and broadly cross-reactive de novo antibodies targeting multiple sarbecoviruses, including those more distantly related to SARS-CoV-2. These antibodies showed greater ability to recognize various viral strains compared to the homotypic nanoparticles in the admixture. Notably, the antibodies generated by these nanoparticles also exhibited stronger binding and neutralizing activity than those induced by conventional homotypic SARS-CoV-2 vaccines.
Overcoming Original Antigenic Sin
Trials have also offered insights into the phenomenon of original antigenic sin (OAS), where the immune system tends to rely on memory cells from an initial exposure when faced with related antigens. The mosaic-8b vaccine can address some of the challenges associated with OAS by generating new antibodies that target a range of sarbecovirus RBDs, rather than merely enhancing the production of existing antibodies specific to certain SARS-CoV-2 strains. This suggests that a single dose of this vaccine could trigger a more broadly protective immune response in individuals who are not immunologically naïve, compared to a single dose of a standard SARS-CoV-2 homotypic vaccine.
While still in early development, the mosaic-8b vaccine represents a promising strategy for broad and cross-reactive immunization against existing and emerging sarbecoviruses, potentially reducing the need for frequent vaccine updates.
