FDA to Assess Glythera Technology for Carbohydrate-Based Conjugate Vaccines

PermaLink couples an antigen to a protein carrier through a biologically and chemically stable bond.

FDA will evaluate the use of technology from Glythera to improve the production and efficacy of conjugate vaccines being developed by the agency. It will apply Glythera’s PermaLink™ technology to the generation of synthetic carbohydrate-based conjugate vaccines and examine its advantages.

Working with the Center for Biologics Evaluation and Research at the FDA, Glythera will adapt the technology to develop new chemistries for the simple and efficient attachment of antigenic carbohydrates, produced synthetically by the FDA, onto carrier proteins.

Generating an immune response against carbohydrates is difficult, owing to their inherently T-cell independent nature, Glythera points out. Typical carbohydrate-based vaccines involve the attachment of a carbohydrate antigen to a protein carrier. The protein carrier enhances presentation of the carbohydrate antigen to the immune system and also helps to activate the helper T cells required by the body to produce antibodies against the carbohydrates.

The chemistry used to attach carbohydrate antigens to the carrier protein can have a major impact on the potency of the vaccine as well as the body’s ability to generate the specific types of long-term memory antibodies required for the immune system to provide protection against the disease. The linker technology in PermaLink is designed to react efficiently with specific amino acids, stably linking a range of functional groups at defined locations on the protein surface, Glythera explains.

PermaLink uses novel chemisty to functionalize surface cysteine residues through a thio-ether bond, stable to biological and chemical degradation. Two classes of PermaLink reagents have been created with efficiency tailored for different sized proteins and peptides. It reportedly provides selectivity and control of PEGylation over maleimide methodology as well as high yields (>95%) for glycosylated/PEGylated peptides.

Glythera is a spin-out biotechnology company from the University of Bath. It also recently entered a collaboration with PATH to employ PermaLink for producing carbohydrate-based conjugate vaccines against pneumococcal disease. Signed on August 2, the agreement calls for the firm to conduct preclinical research to attach antigenic capsular polysaccharides to carrier proteins as a potential alternative conjugation method that could help optimize production of these vaccines.