Extended Polysaccharide Analysis within the Liposomal Encapsulation of Polysaccharides System

Abstract

The Liposomal Encapsulation of Polysaccharides (LEPS) dual antigen vaccine carrier system was assessed across two distinct polysaccharides for encapsulation efficiency, subsequent liposomal surface adornment with protein, adjuvant addition, and size and charge metrics. The polysaccharides derive from two different serotypes of Streptococcus pneumoniae and have traditionally served as the active ingredients of vaccines against pneumococcal disease. The LEPS system was designed to mimic glycoconjugate vaccines that covalently couple polysaccharides to protein carriers; however, the LEPS system uses a noncovalent co-localization mechanism through protein liposomal surface attachment. In an effort to more thoroughly characterize the LEPS system across individual vaccine components and thus support broader future utility, polysaccharides from S. pneumoniae serotypes 3 and 4 were systematically compared within the LEPS framework both pre- and post-surface protein attachment. For both polysaccharides, ≥85% encapsulation efficiency was achieved prior to protein surface attachment. Upon protein attachment with either a model protein (GFP) or a pneumococcal disease antigen (PncO), polysaccharide encapsulation was maintained at ≥61% encapsulation efficiency. Final LEPS carriers were also evaluated with and without alum as an included adjuvant, with encapsulation efficiency maintained at ≥30%, while protein surface attachment efficiency was maintained at ≥~50%. Finally, similar trends and distributions were observed across the different polysaccharides when assessed for liposomal zeta potential and size.

Lipid-Based Nanoparticles for Delivery of Vaccine Adjuvants and Antigens: Toward Multicomponent Vaccines

“…218,219 The end result is a glycoconjugate mimic that offers a simpler, noncovalent form of polysaccharide−protein colocalization and scalable route to full serotype vaccine coverage. 220 In a different study, Li et al used liposomes for the codelivery of 20 Streptococcus pneumoniae polysaccharides and two pneumococcal proteins antigens, GlpO (an α-glycerophosphate oxidase) and PncO (a bacteriocin ABC transporter transmembrane protein), both of which have been shown to provide protection in sepsis and pneumonia challenge models. Protein antigens were used as His Tagged antigens to decorate the surface of liposomes through a modified lipid component DOGS-NTA-Ni.…”

“…In particular, polysaccharides from Streptococcus pneumoniae have been encapsulated into liposomes while the protein antigen is surface exposed on the liposomal surface. Each antigen complements each other as it is associated with a separate progression state of the disease. , The end result is a glycoconjugate mimic that offers a simpler, noncovalent form of polysaccharide–protein colocalization and scalable route to full serotype vaccine coverage …”