A novel antibody-based treatment against Streptococcus pneumoniae
The bacterium Streptococcus pneumoniae is the principal cause of community-acquired pneumonia and can also cause ear infections, sinusitis, meningitis and sepsis. Antibiotics form the main line of defence against these infections, but resistance to them is rapidly evolving.
Antibody cocktail
Monoclonal antibodies are Y-shaped molecules which guide the immune system to tackle pathogenic substances. The EU-funded mABSPN project sought to isolate monoclonal antibodies that could help fight Streptococcus pneumoniae infections. “Current efforts are focused on the development of a novel vaccine,” says mABSPN project researcher Leire Aguinagalde. “These efforts have been successful,” she explains, “yet there is still a great number of cases due to the variability of Streptococcus pneumoniae.” One of the main features of Streptococcus pneumoniae is it has more than 90 polysaccharide capsules. These are one of the main factors which determine virulence and each induces a specific immune response. This large variety means that vaccines do not offer protection against many of them, underscoring the need for more general-purpose treatments. Due to successes in oncology, it is now easier to produce and modify the activity of monoclonal antibodies. For use against Streptococcus pneumoniae, it’s necessary to find an antibody which targets an antigen common to multiple strains, eliciting a potent immune response. An alternative strategy is to produce a cocktail of antibodies that can react to many different strains.
Modified treatment
“Since monoclonal antibodies harness the natural power of the immune system, there is growing interest in using them for the treatment of bacterial infections,” says Aguinagalde. “Plus they don’t have to be specific to one serotype. We focus on antibodies against Streptococcus pneumoniae, however the ultimate goal is to extrapolate the results to target any other bacteria.” Aguinagalde carried out her research at the laboratory of Suzan Rooijakkers at the University Medical Centre Utrecht in the Netherlands, with the support of the Marie Skłodowska-Curie Actions programme. She successfully showed that monoclonal antibodies against pneumococci can be effective, especially when they are modified. “We used some monoclonal antibodies that are already available, and have been able to produce antibodies that can more efficiently recognise pneumococci, completely eliminating them in vitro and in mice,” adds Aguinagalde. To improve the activity of the antibodies, they were modified to provide a better reaction within humans.
Future plans
Support from the EU helped in a number of ways, says Aguinagalde. “It made it possible to combine my knowledge on pneumococci with the host lab’s expertise in immunity. Together we were able to succeed in this project,” she notes. “Thanks to EU funding I had the opportunity to lead and coordinate a project, developing my own project and supervising students. I also attended national and international symposiums, where I could improve my dissemination skills to expert audiences.” The support also gave her more confidence to apply for more competitive grants, she says. Aguinagalde plans to continue working in this field, developing the idea to use monoclonal antibodies to treat bacterial infections: “Now our goal is not just to treat specific pneumococcal strains. We would like to find potent antibodies and enhance their capacity so that eventually we can produce a cocktail of antibodies that could solve the entire problem.”
Keywords
mABSPN, monoclonal, antibody, pneumococci, Streptococcus, pneumoniae, bacteria, cocktail, serotype, infections
