Immune responses to polysaccharide antigens are thymus-independent (TI). Conversion of a polysaccharide antigen to a thymus-dependent (TD) antigen by covalent coupling to an immunogenic protein carrier alters the response to the polysaccharide in several important ways. Of primary importance for the prevention of invasive diseases in infants caused by encapsulated bacteria is the shift of the peak antibody response to a much younger age. Another important change is the development of memory B cells primed and ready to respond to either the polysaccharide, as would be encountered during an infection, or to a second dose of the same antigen. Additional immunoglobulin isotypes not seen or seen as a minor component in response to the polysaccharide are also a feature of the TD response. Finally, the diversity of the antibody population is increased after immunization with a TD vaccine compared with that seen after immunization with a TI vaccine.