In our opinion, the conclusion from all these studies is that pneumococcal polysaccharides in the form in which they have been administered are relatively poor immunogens when compared, for example, to certain proteins such as tetanus toxoid. Had pneumococcal vaccination been the success that might reasonably have been predicted, there would be no argument, this many years later, over its merits. Although polysaccharide vaccines appear to have been effective in mass vaccination programs and in epidemic situations where presumably healthy adults have been involved, it has been more difficult to document their efficacy in individuals who are most in need of them, namely those with aberrant or senescent immune systems. There seems to be no disagreement that antibody at some concentration (the precise level remains to be determined) will, in general, be associated with protection, although in any one individual, for a variety of reasons, infection with a vaccine serotype might still occur. Thus, the clear direction for the future should be not to argue further the merits of currently available vaccine preparations, but rather to work rapidly and efficiently to develop and test new and more effective polysaccharide antigens. Studies in the past 10 years have shown that the polyribosyl ribitolphosphate (PRP) of Haemophilus influenzae type b is a far more effective antigen when conjugated to diphtheria toxoid. For example, in a study in our laboratory, vaccination of healthy young adults with PRP-conjugated diptheria toxoid yielded serum antibody levels 10- to 100-fold higher than after PRP alone. Responses may be even better if other proteins are used. Substantial progress has been made in protein conjugation, at least of certain pneumococcal polysaccharides, and initial trials of such vaccines are soon to be undertaken in human subjects. It will be necessary to prove that higher levels of antibody result and also to show that local reactions in already vaccinated subjects do not preclude the use of conjugated pneumocococcal capsular polysaccharides. The medical profession has sufficient reason to be motivated to develop effective vaccines against pneumococcal infection, as well as reason to be disappointed in the results obtained using existing pneumoccal polysaccharide preparations, that we should welcome the opportunity to evaluate newer vaccines.
