A survey of the literature to date on feeding living attenuated polioviruses for the immunization of man reveals that relatively little has been reported on simultaneous feeding of the three types of virus or the use of mixtures of them as a trivalent vaccine. This is apparently due to the fact that certain strains of poliovirus were found to interfere with the establishment and multiplication of other type strains in the human gut. Thus, Koprowski (1955) reported that type I, SM virus, interfered with the immunizing effect of type II, TN strain, when the two were fed simultaneously. In a subsequent study Koprowski et al. (1956) attempted to overcome this interference by feeding much larger doses of type II virus in a mixture with type I. Again interference was found to occur between the two types, though, under the conditions of the latter study, type I strain was not always dominant.In 1955 Sabin stated that simultaneous feeding of approximately 10 million tissue-culture 50%-infective doses (TCD50) of attenuated polioviruses of all three types to chimpanzees completely suppressed the multiplication and immunizing effect of only type III virus. In 1956 Sabin reported that when he fed approximately one million TCDSO of the naturally occurring attenuated strains (P 2149, P 712, and Glenn) simultaneously, he found no significant interference in four volunteers fed a mixture of types I and II, nor in three volunteers fed a mixture of types I and III, nor in three persons fed types II and III, nor in one person fed all three types together. He did note that, in some of the individuals fed, the appearance of antibodies was delayed and titres were in the lower range. In later studies carried out with his " optimum single plaque" strains, Sabin (1957) reported that the type II strain was the dominant one and that quite often, though not always, it interfered with the multiplication of the other two types when fed as a mixture. This finding prompted him to state that " immunization against all three types of poliovirus by a single administration of a mixture of them is not feasible" (Sabin, 1958). He therefore recommended that his three " optimal " strains be fed separately at intervals of thtee weeks in the order of types I, III, and II.

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Sugg and Harris and their respective coworkers were the first to study extensively the immunologic properties of a strain of pneumococcus closely related to, but not identical with, typical strains of Type III pneumococci (1, 2). The " Thomas " strain of these workers now can be classified definitely as a Type VIII pneumococcus, according to the classification of Cooper et al. (3). Both the Thomas strain and the Type VIII strains were shown, by these respective investigators, to produce in certain animal species antibodies of high titer against typical strains of Type III pneumococci. The titers were sometimes higher than the notoriously low homologous antibody titers obtainable by the injection of typical Type III strains. The reciprocal serological relationships between typical Type III strains and the related Type VIII strains were demonstrated with regard to passive protection in mice, agglutination, and precipitation. Antibody relationships similar to those described in the sera of lower animals were shown, by Finland and Winkler (4), to occur also in the sera of certain human subjects during convalescence from pneumonia due to these types. With regard to " natural antibodies," as measured by the pneumococcidal power of the whole defibrinated blood or the protection afforded mice by the serum of normal human subjects, Finland and Sutliff found no such reciprocal relationship (5).The specific carbohydrate from Pneumococcus Type VIII was recently isolated and its properties described by Brown (6

The circumstance that rabies is potentially an increasing threat to certain population groups has led to efforts to develop a safe means for primary immunization. The

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