Pipeline & Technologies

Overview

Conjugate vaccines are among the most effective vaccines available today to prevent bacterial diseases, such as pneumococcal and nosocomial infections. Approximately 25%-30% of the global vaccine market comprises conjugated vaccines with sales between seven and eight billion dollars in 2010. However, due to the complexity of current technology, there are several bacterial pathogens, such as Staphylococcus aureus, for which there are no vaccines to date. GlycoVaxyn's mission is to overcome these challenges by utilizing its proprietary recombinant DNA technology to create the next generation of conjugate vaccines.

 

Bioconjugate Vaccine Technology

The production of conjugate vaccines can be simplified, streamlined and become more cost effective.

GlycoVaxyn has developed a proprietary recombinant DNA technology that for the first time enables the in vivo synthesis of novel and well characterized immunogenic polysaccharide/protein complexes for use in vaccines in an efficient and cost-effective manner. The technology utilizes validated and well understood recombinant DNA techniques along with patented genes to produce "natural" carbohydrate-protein conjugates or bioconjugates that can be used as vaccines. GlycoVaxyn's bioconjugates can produce functional antibodies that protect against diseases in animal models.

In GlycoVaxyn's patented process, the gene cluster responsible for the biosynthesis of the bacterial LPS, capsule polysaccharide (CPS) or oligo polysaccharides (oligo PS) is transformed into E. coli together with the protein carrier of interest along with GlycoVaxyn's patented enzyme that performs the bioconjugation reaction in vivo. Once produced upon induction, simple purification steps are performed and the biological products are formulated for use as a vaccine. The process of recombinant bioconjugation preserves the bacterial carbohydrate's and protein's native structure and only produces specific conjugates with a known number of conjugated components. This process yields highly reproducible batches.
Figure 1 illustrates the bioconjugation process.

Figure 1: In vivo glycosylation system for production of bioconjugates

The key advantages of GlycoVaxyn's technology platform are:

• Versatility across pathogens and conjugates as it enables the combination of any polysaccharide antigen with any protein antigen, allowing maximum flexibility in custom engineering vaccines; can both target new diseases or produce an enhanced immune response
• Ability to deliver highly immunogenic vaccines by expressing polysaccharide epitopes in their most native (natural) conformation and combining them with the most immunogenic protein carriers also in a well-defined and preserved natural conformation
• A straightforward and reproducible manufacturing process and batch-to-batch consistency that minimizes development costs as well as time to market

The technology has broad potential applications in the field of bacterial vaccines but also in viral and cancer vaccines and human therapeutic proteins.

Current Chemical Conjugate Technology (Figure 2)

Available conjugate vaccines are developed and manufactured by employing a chemical conjugation process. The present chemical conjugation methods involve:

• Varoius polysaccharides and proteins that are purified from fermented bacteria through multiple steps.
• In the case of the bacterial lipopolysaccharide (LPS) component, an additional cleavage and purification step is performed.
• Once the target bacterial polysaccharide and carrier protein components have been isolated and purified, they are ready to be chemically cross linked and purified for use as a conjugate vaccine.

The product of this type of conjugation is variable, leading to a mix of proteins with one or more polysaccharides conjugated to each protein. The chemical process may also alter the natural configuration of the carbohydrate and / or protein thereby decreasing the efficacy of the final product.

Figure 2: In vitro glycosylation process for the production of chemical conjugates