Synthetic design of Streptococcus pneumoniae 6A/6C oligosaccharides for vaccine development

Streptococcus pneumoniae (SPn) is a Gram-positive bacterium that is a major cause of lifethreatening infections such as pneumonia, sepsis, and meningitis1. The bacterium’s ability to resist immune attack is largely due to its polysaccharide capsule (CPS). Vaccination is considered by the World Health Organization (WHO) to be the most cost-effective way to prevent bacterial infections. Polysaccharide conjugate vaccines (PCVs) have been highly successful in reducing the incidence of invasive pneumococcal diseases caused by the serotypes included in the vaccines. However, the growing prevalence of infections caused by non-vaccine serotypes (NVTs), a process known as serotype replacement, has diminished the effectiveness of these vaccines. For carbohydrate-based vaccines to be effective, the saccharide fragment must be conjugated to an immunogenic protein to stimulate a T celldependent immune response. However, the large amount of carrier protein used in multivalent vaccines, can lead to a weakened immune response due to the pre-existing anti-carrier immunity. This background underscores the importance of identify new antigens capable of eliciting immunity that can protect against multiple serotypes. A clear example of this is seen in serogroup 6: following the widespread use of vaccines targeting serotypes 6A and 6B, there has been a significant increase in infections caused by non-vaccine serotype 6C; despite the minimal structural differences2. The main goal of this project is to synthesize hybrid structures combining elements of the 6A and 6C CPS (compounds 1–4, Fig. 1). Another key objective of this project is the design and synthesis of a chimeric structure that integrates the repeating units of both SPn 6A and 6C. The synthesized oligosaccharides will be attached to a carrier protein, and will be subjected to immunological analysis.