A peptide-free, liposome-based oligosaccharide vaccine, adjuvanted with a natural killer T cell antigen, generates robust antibody responses in vivo

Abstract

Due to the prevalence of oligo- and polysaccharides on the surfaces of pathogenic organisms, carbohydrates are primary targets for recognition by antibodies generated by the immune systems of higher organisms. Consequently, substantial effort has been expended in efforts to develop vaccines based on carbohydrate epitopes. Typical approaches involve multivalent presentation of carbohydrate targets on antigenic peptides or proteins, which often involve substantial synthetic commitments and/or vaccines that are heterogeneous and difficult to characterize. We have developed a simple, liposome-based approach to generate multivalent carbohydrate vaccines, and in place of an antigenic peptide or protein, we have used a potent antigen for natural killer T cells. This vaccine, based on the Streptococcus pneumoniae serotype 14 polysaccharide, gave a response superior to that from a clinically used vaccine (Prevnar). The dependence of this response on liposome formation was demonstrated by comparison to a simple mixture of the oligosaccharide and the natural killer T cell adjuvant. The importance of the strength of the adjuvant was observed by use of a potent synthetic adjuvant and a weaker, bacterial derived glycolipid adjuvant. These results demonstrate the effectiveness of this novel and relatively simple means of generating carbohydrate-based vaccines.