Improving vaccines against Streptococcus pneumoniae using synthetic glycans
More about Open Access at the CrickAuthors list
Paulina Kaplonek Naeem Khan Katrin Reppe Ben Schumann Madhu Emmadi Marilda P Lisboa Fei-Fei Xu Adam DJ Calow Sharavathi G Parameswarappa Martin Witzenrath Claney L Pereira Peter H SeebergerAbstract
remains a deadly disease in small children and the elderly even though conjugate and polysaccharide vaccines based on isolated capsular polysaccharides (CPS) are successful. The most common serotypes that cause infection are used in vaccines around the world, but differences in geographic and demographic serotype distribution compromises protection by leading vaccines. The medicinal chemistry approach to glycoconjugate vaccine development has helped to improve the stability and immunogenicity of synthetic vaccine candidates for several serotypes leading to the induction of higher levels of specific protective antibodies. Here, we show that marketed CPS-based glycoconjugate vaccines can be improved by adding synthetic glycoconjugates representing serotypes that are not covered by existing vaccines. Combination (coformulation) of synthetic glycoconjugates with the licensed vaccines Prevnar13 (13-valent) and Synflorix (10-valent) yields improved 15- and 13-valent conjugate vaccines, respectively, in rabbits. A pentavalent semisynthetic glycoconjugate vaccine containing five serotype antigens (sPCV5) elicits antibodies with strong in vitro opsonophagocytic activity. This study illustrates that synthetic oligosaccharides can be used in coformulation with both isolated polysaccharide glycoconjugates to expand protection from existing vaccines and each other to produce precisely defined multivalent conjugated vaccines.
Journal details
Volume 115
Issue number 52
Pages 13353-13358
Publication date
Full text links
Publisher website (DOI) 10.1073/pnas.1811862115
Europe PubMed Central 30530654
Pubmed 30530654
Keywords
Type of publication