Pneumococcus is a major human pathogen causing pneumonia and is responsible for a large number of deaths worldwide among young children and old adults. Its virulence is mostly due to its carbohydrate capsule, which encases the pneumococci and shields them from the host immune system. Antibodies to the capsule can kill pneumococci and protect us from infections. Because our body can make these antibodies if the capsule is injected into us, the capsule is useful as a vaccine against pneumococcal infections. Pneumococci can express almost 100 types of capsule, but actual vaccines contain 10-23 common capsule types (serotypes). Following the widespread use of these vaccines however, serotypes absent from the vaccine have become more common, and vaccines have become less effective overall. To understand how pneumococci can evade vaccines, and to improve these vaccines, my laboratory studies diversity and immunity to the pneumococcus capsule. Our studies of capsule diversity have led us to discover many new and important capsule types. Our discovery of serotype 6C showed how pneumococci can evade pneumococcal vaccines and has provided knowledge essential to vaccine design. Our discovery of 11E showed that innate immunity can recognize capsule and induce changes in capsule-making genes as pneumococci adapt to live in different body niches. It also showed that innate immunity can recognize variable pathogen structures and how pneumococci adapt to different niches of the body. We are now investigating how completely the capsule encases a bacterium. If the capsule leaves some areas of the pneumococcal surface exposed, then the molecules in the exposed areas can be useful as new vaccines. To do this, we are currently studying bacterial capsules and their synthesis with new super-resolution microscopy, which can visualize down to molecular dimensions. Our studies of immunity to the capsule showed that some vaccines can elicit non-functional antibodies. Thus, vaccine development can be simplified if antibodies can be tested directly for their function. We have developed a practical way to measure antibody function by inventing MOPA (Multiplexed OpsonoPhagocytic Assay). MOPA has become essential in improving pneumococcal vaccines and has simplified vaccine manufacture and evaluation. MOPA is now facilitating production of low cost pneumococcal vaccines available for the entire world. Our laboratory has been serving as a reference laboratory to the World Health Organization in this field.
