| Autor: |
Hill AB; Abcombi Biosciences Inc. , 1576 Sweet Home Road , Amherst , New York 14228 , United States.; Department of Chemical and Biological Engineering , University at Buffalo, The State University of New York , Buffalo , New York 14260 , United States., Beitelshees M; Abcombi Biosciences Inc. , 1576 Sweet Home Road , Amherst , New York 14228 , United States.; Department of Chemical and Biological Engineering , University at Buffalo, The State University of New York , Buffalo , New York 14260 , United States., Nayerhoda R; Department of Biomedical Engineering , University at Buffalo, The State University of New York , Buffalo , New York 14260 , United States., Pfeifer BA; Department of Chemical and Biological Engineering , University at Buffalo, The State University of New York , Buffalo , New York 14260 , United States.; Department of Biomedical Engineering , University at Buffalo, The State University of New York , Buffalo , New York 14260 , United States., Jones CH; Abcombi Biosciences Inc. , 1576 Sweet Home Road , Amherst , New York 14228 , United States. |
| Abstrakt: |
We detail the development of a next-generation Streptococcus pneumoniae liposomal encapsulation of polysaccharides (LEPS) vaccine, with design characteristics geared toward best-in-class efficacy. The first generation LEPS vaccine, which contained 20 encapsulated pneumococcal capsular polysaccharides (CPSs) and two surface-displayed virulence-associated proteins (GlpO and PncO), enabling prophylactic potency against 70+ serotypes of Streptococcus pneumoniae (the causative agent of pneumococcal disease), was rationally redesigned for advanced clinical readiness and best-in-class coverage. In doing so, the virulent-specific GlpO protein antigen was removed from the final formulation due to off-target immunogenicity toward bacterial species within the human microbiome, while directed protection was maintained by increasing the dose of PncO from 17 to 68 μg. LEPS formulation parameters also readily facilitated an increase in CPS valency (to a total of 24) and systematic variation in protein-liposome attachment mechanisms in anticipation of clinical translation. An additional safety assessment study demonstrated that LEPS does not exhibit appreciable toxicological effects even when administered at ten times the effective dose. In summary, this new design offers the broadest, safest, and most-complete protection while maintaining desirable glycoconjugate-like features, positioning the LEPS vaccine platform for clinical success and a global health impact. |
