RIGID MOLECULAR LINKER INCREASES PNEUMOCOCCAL HYBRID PROTEIN STABILITY AND ANTIBODY PRODUCTION IN MICE
Pneumococcal protein-based vaccines that would offer serotype-independent protection have been investigated in order to increase coverage and reduce serotype replacement. Among them, PspA (pneumococcal surface protein A) and PdT (detoxified pneumolysin) have shown promising results in animal models. This work aimed at producing a stable hybrid protein of PspA and PdT capable of being used in the formulation of a novel pneumococcal vaccine, which brings the advantage of producing two antigens in a single process. These proteins were genetically fused with and without molecular linker. Although both hybrids showed the same protection against lethal challenge in mice, the hybrid with linker showed greater molecule stability and higher antibody production. This stability improvement allowed the production of the hybrid molecule in 10 L bioreactors and its purification up to 95% of purity. These results show the great potential of molecular linkers in protein engineering.