a1 The David Bruce Laboratories, East Everleigh, Marlborough, Wiltshire
In seeking a more satisfactory test than the conventional mouse-protection tests for the assessment of typhoid-paratyphoid vaccines in relation to their O and Vi antigens, it was decided to undertake a series of experiments with vaccines containing the somatic antigens of Salmonella paratyphi C and to use this organism to challenge mice thus immunized. Salm. paratyphi C contains the same Vi antigen as Salm. typhi and moreover it is capable of giving rise to a true infection in mice in contrast to the acute intoxication which follows a fatal dose of Salm. typhi.
Large doses, of the order of 100 × 106, of this paratyphoid organism injected intraperitoneally into mice resulted in acute intoxication with death in 24–72 hr., similar in every way to the picture with typhoid bacilli, but when the dose was reduced 100-fold or more an infective illness was set up which after an interval of 5–10 days or more, during which the organisms multiply freely in the tissues, terminated fatally. Typhoid bacilli do not produce a true infection in mice.
Living vaccines were prepared of Salm. typhi Ty6S (an almost pure Vi strain) and Salm. cholerae-suis (contains the same O-antigen complex as Salm.paratyphi C). These were used separately, and in combination, to immunize different batches of mice by the subcutaneous route against a subsequent intraperitoneal challenge with a Vi-positive culture of Salm. paratyphi C at both high- and low-dose levels. The different challenge doses were to assess the relative values of the 0 and Vi components in protecting against intoxication (high dose) and infection (low dose), respectively.
Against intoxication pure Vi vaccines were almost as effective as Vi + O vaccines, whereas pure O vaccines gave little or no protection.
Against fatal infection the combined Vi + O vaccine offered good protection and the pure O vaccine was but little inferior, whereas the pure Vi vaccine appeared to be without significant effect.
Quite small doses of Salm. paratyphi C administered by the intra-gastric route can give rise to a general infection in mice, but in order to obtain consistent results much larger doses were found necessary (about 300 x 106 organisms). Mice immunized with the same three vaccines and subsequently challenged by the intragastric route with this large dose showed significant protection throughout. The combined, O + Vi, vaccine did not appear to have any advantage over the pure O vaccine, but both were markedly superior to the pure Vi vaccine. Further experiments on the same lines are however necessary to see if the results obtained in this single experiment are reproducible.
The relationship of the above findings to the evaluation of agents employed in man for the prophylaxis of enteric fever and the need for further experimental work of a similar nature are discussed.
We wish to thank Dr F. Kauffmann for strains of Salm. paratyphi C, Lt-Col. T. E. Field, whose results we have freely quoted, and Dr S. Peto for advice on statistical evaluation of our results.
(Received October 30 1956)
p1 Present address: The Wright-Fleming Institute of Microbiology, St. Mary's Hospital Medical School, London, W. 2.