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Immunity in typhoid fever. I. The anti-typhoid vaccine of Wristh, 1896 to 1979

The present comprehensive review deals with the available literature on anti-typhoid vaccines. Among the biological products, no other has raised as much controversy regarding efficacy as this commom preventive, since its early introduction by Wright, Pfeiffer & Kole. From the beginning the lack of an adequate experimental procedure for testing the vaccine potency was felt, and only poor and partial data were gathered, both from human and animal models, in relation to the basic immunological mechanism of the response to vaccination. For this reason a number of different methods have been proposed and used leading to variations in such aspects as: a) the nature of bacterial strains for preparing the vaccine; b) the handling of vaccine strains-killed by heat, various chemicals (alcohol, ether acetone) or lysed, or employing avirulent strains; c) the addition of different components (preservatives and related microrganisms); d) the route of application (subcutaneous, intradermal, oral, etc); e) the dose (number of organisms); f) the time schedule for application. Many field trials failed to be conclusive. It is considered that the early field trials lacked proper controls, which were introduced later, in the well planned investigations sponsored by World Health Organization, in several parts of the World (Yugoslavia, Poland, U.S.S.R., India, Tonga). Data available from such trials permitted the following conclusions: a) killing of the vaccine strains by ethanol produced a vaccine of weak prophylactic value, if any; b) killing by other means produced protective vaccines, with advantage for the one treated by acetone; c) the doses of S. paratyphi A and S. paratyphi B put together in the usual TAB vaccination were insufficient. With a larger dose, protection was obtained in relation to S. paratyphi B; d) no good correlation was obtained between animal tests and protection in humans. Also, titers to the O, Vi and H antigens did not bear a direct relationship with the vaccine protective effect; e) one dose of the acetone killed vaccine (0.5 - 1.0 ml of a 10*9 ml bacterial suspension), subcutaneously, gave appreciable protection for a short period of time, which improved with two doses, four weeks apart; f) better protection was observed in young people, as compared with the older; g) no protective effect was detected when a killed oral vaccine (Typhoral) was used. Some experiments with animals (mice, chimpanzees) and human volunteers indicated a better protection being conferred by live attenuated vaccines. However, in some experiments persistence of both vaccine and challenge strains was observed as well as a significant relation between the rough vaccine strain used for the purpose and abacterial renal lesions of unknown origin.


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