Can a novel multi-epitope, serotype-independent pneumococcal vaccine confer protection against human carriage and transmission?

Summary 

Young children, older individuals and immune-compromised individuals are at greater risk of developing pneumonia caused by the bacterium Streptococcus pneumoniae (pneumococcus). At any given time, approximately 10-20% of adults are colonised with pneumococcus in the upper respiratory tract but colonisation with the bacterium does not cause any symptoms. However, when immune defence mechanisms in the respiratory mucosa break down, the risk of developing pneumococcal disease increases.

Our research team has developed an experimental human pneumococcal challenge model. Here, a defined number of pneumococci are introduced into the nose of healthy adults who are then carefully monitored to determine whether their upper respiratory tract becomes colonised with the bacterium. The model allows us to test whether immune responses to pneumococcal antigens are associated with protection and thus determine novel vaccines should move into phase I clinical trials. Here we propose to determine the frequency and phenotype of antibodies and cellular responses to a multi-epitope protein vaccine which targets critical virulence factors of pneumococci. The results of the study will inform whether this novel vaccine correlates with protection from pneumococcal colonisation.

Project Outcomes 

Young children, older individuals and immune-compromised individuals are at greater risk of developing pneumonia caused by the bacterium Streptococcus pneumoniae (pneumococcus). At any given time, approximately 10-20% of adults are colonised with pneumococcus in the upper respiratory tract but colonisation with the bacterium does not cause any symptoms. However, when immune defence mechanisms in the respiratory mucosa break down, the risk of developing pneumococcal disease increases.

Our research team has developed an experimental human pneumococcal challenge model. Here, a defined number of pneumococci are introduced into the nose of healthy adults who are then carefully monitored to determine whether their upper respiratory tract becomes colonised with the bacterium. We used this model to test whether immune responses to pneumococcal antigens are associated with protection against a novel multi-epitope protein vaccine which targets critical virulence factors of pneumococci. We tested whether we could detect antibody responses in the nose and antibodies, B cells and T cells in blood targeting the multi-epitope vaccine. We observed that the multi-epitope vaccine was recognised by antibodies and B cells. However, the magnitude of the response was comparable between study participants who became pneumococcal carrier and those who did not before intranasal challenge with the bacteria, suggesting that immune responses against the vaccine are not associated with protection.