Molecular Modelling of STREPTOCOCCUS PNEUMONIAE Carbohydrate Antigens for Optimizing Vaccine Design

Streptococcus pneumoniae is a Gram-positive pathogen that commonly colonizes the human nasopharynx and is a leading cause of invasive pneumococcal disease (IPD), including pneumonia, otitis media, bacteraemia, and meningitis. Globally, lower respiratory tract infections account for approximately 2.74 million deaths annually, with 704,000 occurring in children under five years old. In Africa, S. pneumoniae is responsible for 33% of childhood pneumonia deaths.

Pneumococcal serotypes are differentiated by their capsular polysaccharides (CPS), the primary targets of current pneumococcal vaccines (PCVs). While first- and second generation PCVs have successfully reduced disease burden caused by vaccine-serotypes, they have also led to an increase in infections by non-vaccine serotypes due to serotype replacement – such as those in serogroup 33. The ongoing serotype replacement is now driving the development of third generation vaccines that seek broader protection by expanding capsular coverage, incorporating conserved protein antigens, or using combination strategies.

Our project uses molecular modelling to study the conformations of S.pneumoniae polysaccharide antigens. This research establishes a basis for examining potential cross-protection among serotypes within Serogroup 33 by identifying antigens that may trigger cross-reactive immune responses. The goal is to support the rational design of next-generation pneumococcal conjugate vaccines (PCVs) to maximize protective coverage with minimal antigen components , thereby improving vaccine efficacy and reducing manufacturing costs.