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1. The most virulent strains ofSalmonella typhiare those that develop both the Vi and O antigens in maximum quantities.2. The Vi antigen is not a particularly toxic substance; it is less toxic for the mouse than the O antigen.3. The main biological function of the Vi antigen is to protect the O antigen against the action of the natural or immune O antibody, thereby protecting the bacterial cell against phagocytosis and the bactericidal action of the serum.4. The relative virulence for mice of freshly isolated strains ofSalmonella typhireflects their virulence for man.

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IN previous work on the bactericidal action of serum (Felix and Olitzki, 1926) it has been shown that strains of B. typhosus and B. paratyphosus A which lare highly sensitive to 0 agglutinins are also highly susceptible to the bactericidal action of serum. Strains of this type are killed by normal sera so easily that they cannot be used a t all in bactericidal tests with inactivated and complemented immune sera. This correlation is quite consistent with the theory that bactericidal action and 0 agglutination are due to the same 0 antibody.From this observation it seemed justifiable to assume that strains of B. typhosus of the sensitive type are less virulent than non-sensitive or inagglutinable strains, which are resistant to the action of the 0 antibody. To test this hypothesis the mouse was selected as experimental animal since Grinnell (1932) and Perry, Findlay and Bensted (1933 a and b) have shown that entirely regular results are obtained when mice are used for virulence tests with B. typhosus. Xelection of sensitive and non-sensitive strains.It is now generally recognised that the " inagglutinable " or " hypo-agglutinable " cultures of B. typhosus, which are often met with amongst cultures freshly isolated from the blood of typhoid patients, are " apparent " 0 variants (Felix 1924). They are readily agglutinated by anti-0 sera and on subculture on moist agar soon develop abundant flagella and consequently are agglutinated to full titre by anti-H sera. This " inagglutinability," therefore, is an evanescent phenomenon, due to the temporary suppression of flagella and H antigen. True 0 variants, permanently non-motile and devoid of H antigen, have not yet been found amongst freshly isolated cultures of B. typhosus.There exist, however, between different strains of B. typhosus striking differences in agglutinability by 0 agglutinins, which have not yet attracted much attention. Weil and Felix (1920) first described such differences. The strain B. typhosus 901, outstanding for its remarkable agglutinability, was then recommended as a specially sensitive reagent for 0 agglutinins and is now being used in the 409

1. Rough variants, derived from strains of B. typhosus which possess the Vi antigen, may still contain this antigen though the smooth O antigen has been lost.2. Such variants, which are non-virulent, are yet capable of inducing active and passive immunity.3. The virulence of B. typhosus depends on the combined activity of the smooth O and the Vi antigen. Nevertheless the Vi antibody alone is sufficient to protect against infection with strains of the highly virulent type.4. The use of avirulent, rough, but Vi-containing variants as vaccines and in the preparation of therapeutic sera is discussed.