The goal of this project was to unravel whether complement-enhancing monoclonal antibodies can be se as a new therapeutic approach against the gram-positive bacteria Streptococcus pneumoniae (pneumococcus). One third of the annual deaths occurring in the word are estimated to be due infectious diseases and, particularly, respiratory infections are responsible of the death of 4 million people every year. According to World Health Organization (WHO), pneumonia kills more children worldwide than any other disease, being S. pneumoniae the most common cause of sever pneumonia among children under 5 years old in developing countries, as well as in children and adults over 60 years in Europe and the Unites States. Pneumococcus, is indeed the main cause of community acquired pneumoniae, non-epidemic bacterial meningitis and acute otitis media, as one of the major causes of bacterial sepsis. The search of effective treatments to fight against infectious diseases has been, since many years, among the main challenge of medicine. To reduce the great impact on morbidity and mortality of S. pneumoniae world-wide, health care efforts over the past 50 years have concentrated on the development of serotype-specific vaccines. Current available vaccines target the polysaccharide capsule (CPS), which is considered the most important virulence factor of pneumococcus due its role preventing phagocytosis killing and its variability. There are more than 90 different capsule serotypes described so far that induce a type-specific immune response. Although widespread vaccination has been proven highly effective for lowering invasive pneumococcal disease (IPD), a major contributing factor for the still large burden of disease is the limited serotype coverage provided by current vaccines and the associated emergence of IPD caused by non-vaccine serotypes, however other factors are also at play. These includes, poor immunogenicity of some serotypes and the uncertainly efficacy of current immunization practice in high-risk groups. Finally, the emergence of strains with high level of antibiotic resistance is jeopardizing the use of antibiotic therapies and highlights the strong need to develop new therapeutic strategies against pneumococcal infections. In this project we study whether monoclonal antibodies against S. pneumoniae that improve the activity of our immune system can be used as therapeutic antibodies. Because complement activation is crucial for antibody-dependent killing of S. pneumoniae, development of complement-activating antibodies represents an attractive strategy for antibacterial therapy. Therefore, the main objectives of this projects include the identification of antibodies against S. pneumoniae driving potent complement activation and unravel whether monoclonal antibodies eliciting complement are effective in pneumococcal killing. At its conclusion, this project shows that the use of complement-enhancing antibodies is a promising new therapeutic approach against S. pneumoniae infections.
