D-Crypt™
Premas specializes in developing recombinant proteins for vaccine development. Such proteins are often “difficult to express proteins” (DTE-Ps). Our innovative Saccharomyces cerevisiae-based D-Crypt™ platform is optimized for high-yield production of DTE-Ps. The platform allows the expression of each of these DTE-Ps individually or collectively, in different combinations. The ability to express multiple surface antigens simultaneously improves the likelihood of generating an efficacious vaccine.
The D-Crypt ™ platform has previously scaled multi-component protein systems successfully and applied them to vaccine development. Our platform is the only example to have expressed more than 30 different type-1 membrane proteins, including the Influenza virus NA protein and the Rotavirus spike protein. Our success in expressing the large, complex NA protein, gives us confidence that we can produce the multiple antigenic membrane proteins.
Virus Like Particles (VLP)
D-crypt™ –has been used for Virus-like particle (VLP) vaccine candidate generation. The world’s first triple antigenic VLP vaccine for SARS-CoV2 was developed using the platform and proved to be safe and effective in a Phase 1 clinical trial study. Further, H1N1 and H5N1 triple antigenic (HA+ full-length NA+M1) VLPs have also been produced successfully for Influenza. Immune response has been observed for H1N1 VLPs in preclinical studies, indicating H1N1 VLPs as a promising candidate for flu.
The D-crypt™ platform generates VLPs from various virus families with relative ease, with 9-12 months to clinical material or less.
CircRNA - VLP
Premas has stepped into the challenging area and developed a ‘proof-of-concept’ for directed in-situ encapsulation of circular cargo mRNA of therapeutic importance in recombinantly produced VLPs using the D-crypt™’ platform. Our study has shown successful generation of VLPs, (100-120nm) with high copy in vivo entrapment of CircRNA cargo as confirmed through qPCR method. This has been studied further for immunogenicity response in mice. Interestingly, CircRNA cargo has produced high IgG response. This depicts its successful enhanced and stable protein expression in mice through host specific IRES which resulted in increased copy template and high immune response.
Our CircRNA-VLP vaccine consists of triple antigenic (HA+NA+M1) Influenza VLP with cargo Circ-RNA encoding for Prefusion F antigen of RSV.
The recombinant production of CircRNA vaccines offers enhanced RNA vaccine development, incorporating IRES and ORF for efficient protein expression. These vaccines boast a greater half-life than linear mRNA counterparts, which face RNase-induced degradation. Our D-Crypt platform is engineered for the production of thermostable virus-like particles (VLP) and CircRNA-VLP vaccines. This is achieved through lyophilizing the VLP-CircRNA complex. Further, RNA encapsulated in VLPs is generated within yeast cells, bypassing complex in vitro production.