BioSavita technology platform includes genetically engineered Saccharomyces cerevisiae (S. cerevisiae) yeast strains and plug-and-play multicopy yeast expression vectors designed for simultaneous production of multiple antigens.
Glycoengineered BioSavita Yeast
BioSavita's proprietary S. cerevisiae strains were engineered for modified N-glycosylation with only core endoplasmic reticulum (ER) glycan as conserved in all eukaryotes. There is no hyper-mannosylation in products from these yeast strains.
Yeast have several advantages when compared with current processes used for vaccine production, including (i) FDA approved process for large scale vaccine production (ii) Rapidly and scalable shorter production cycle (that may provide a new vaccines for the Covid-19 pandemic threat) (iii) available microbial fermentation facilities with low operating costs throughout the world (iv) neither viral nor endotoxin contamination thereby reducing purification and quality control costs.
BioSavita “Yeast Factories”
BioSavita uses synthetic biological approaches and provides a platform for construction of “yeast factories” for the accelerated and cost-effective production of recombinant antibodies, proteins and VLP vaccines. Using our yeast platform, we have produced complex multimeric proteins such as hemoglobin, antibodies, antibody-fusion proteins, Ebola Z-Mapp antibodies and Ebola VLPs.
Virus-Like Particle (VLP) Vaccines
VLPs are protein-lipid complexes and contain one or more proteins that are able to self-assemble into structures that have similarities to their corresponding native viruses. The organized and repetitive structure of a VLPs often provides enhanced immunogenicity than purified protein antigens used in subunit vaccines. VLPs do not contain viral genomic material and therefore considered safe during manufacturing and for the administration to patients. The repetitive display of epitopes on VLPs and its adjuvant properties are capable of inducing potent humoral and cellular immune responses. Yeast have been used successfully to produce VLP vaccines for non-enveloped viruses, such as the HPV and HepB. BioSavita has demonstrated secretion of VLPs from enveloped virus such as Ebola and is now developing VLPs from another enveloped virus, SARS-CoV-2.
BioSavita’s Rapid, Scalable Yeast Production Platform for Covid-19 Vaccine Development
The patented platform includes genetically engineered S. cerevisiae yeast strains and plug-and-play multicopy yeast expression vector designed for the simultaneous production of multiple antigens. Using this strategy, we have produced recombinant hemoglobin's, antigens, proteins, antibodies and Ebola VLPs from our yeast.
The yeast process for manufacturing the vaccines is cost-effective and can use existing microbial plants and be adapted to cGMP production to an approved CMO anywhere in the world to rapidly address emerging global pandemics. The yeast has self-adjuvant properties and therefore yeast produced VLPs are expected to have enhanced functional immunity, which can lead to better protection against Covid-19.
BioSavita’s yeast platform contains three components that are critical for successful production of a wide variety of VLPs:
1. The ability to express multiple proteins using proprietary expression vectors
2. Genetically engineered yeast strains that secrete complex multimeric proteins in media
3. The development of glycoengineered strains that do not hypermannosylate secreted proteins but can create an array of glycoforms that may enhance the antigenicity and immunogenicity of the VLPs.
Moreover, the cost-effective scalability of the yeast system and its high throughput compatibility makes VLP manufacturing a viable economic proposition.
Multivalent VLP Vaccines
Using our twin-cassette expression system and diploid yeast strategy, our objective is to develop multivalent Covid-19 vaccine that includes the S, M and E antigens.
The classical genetics of S. cerevisiae yeast allows generation of two distinct mating types of BioSavita yeast strains (a and alpha) which are engineered for secretory production of recombinant proteins. We plan to express two antigens of SARS-CoV-2 in the “a” yeast strain and two separate SARS-CoV-2 antigens in the “a” yeast strain. Mating of the “a” and “alpha” strains can produce diploid yeast carrying up to four genes producing VLPs for multiple antigens in one strain as shown in next figure.
Advantages of BioSavita’s Monoclonal Antibody
Our twin-cassette vectors allows simultaneous and equimolar expression of the heavy and light chains of an IgG to produce a fully assembled molecule. Yeast can perform post-translational modifications of IgG. In addition, the secreted IgG do not show hypermannosylation. Yeast fermentation production cycles are shorter than other systems. Furthermore our plasmids are stable at high cell density. The secreted IgGs are free from endotoxins and animal viruses.
Examples of mAbs from the BioSavita yeast platform include Ebola antibodies (cDNAs received from Mapp Biological, Inc.) and anti-CD52 IgG (Biosimilar Campath) as shown.
Granulocyte-macrophage colony-stimulating factor (GM-CSF) functions beyond its original identification as an inducer of granulocyte and macrophage development from progenitor cells. GM-CSF has been identified as a potential target in many inflammatory/autoimmune conditions. GM-CSF may be useful as an adjuvant for a number of vaccines, such as influenza, HIV and cancer. GM-CSF can be produced in high yield in BioSavita yeast as shown below.