Pneumococcus is the quintessential encapsulated human pathogen. 15 The pneumococcal capsule was identified early as the major virulence factor in many animal experiments. Vaccine development was attempted from the beginnings of pneumococcal research but was hampered by a lack of understanding of the diversity of capsular types. Neufeld's finding that strains could by typed with specific antisera by the capsular" swelling" test opened the door to serum therapy, to new fields of irnmunology and bacterial biochemistry, and eventually to the development of polysaccharide vaccines.

Many early experiments showed that killed or disrupted pneumococci or culture filtrates caused inflammation similar to that of infection with live cells. Cell wall constituents proved to be important virulence factors. The activity of powerful toxins was also observed and identified variously as hemolysins, leukotoxins, and the purpura-producing principle. The toxic effects were probably all attributable to what is now known as pneumolysis