The preparation, testing and standardization of typhoid vaccine

Abstract

1. The review of the laboratory evidence published since the introduction, ten years ago, of the alcohol-treated typhoid vaccine furnishes additional support for abandoning the old method of making typhoid vaccine. The alcohol-treated vaccine has advantages in regard to both the Vi-antibody response and the degree of systemic reactions produced.2. The technique of the preparation of alcohol-killed and alcohol-preserved typhoid-paratyphoid vaccine has remained as originally described. The methods of selecting the vaccine strains and routinely examining the cultures have also remained unchanged.3. The necessity of testing typhoid vaccines not only by active-immunity tests in mice but also for their antibody-stimulating properties is again stresssed. These tests consist of immunization of rabbits, estimation of their Vi- and O-agglutinin titres and passive-immunity tests in mice.4. The most important sources of error in mouse-protection tests are:(a) the use of a test culture of less than the maximum degree of mouse-virulence;(b) the use of the mucin technique;(c) immunization by intraperitoneal injections when the challenge dose also is given by this route.Much of the experimental work on typhoid vaccine has been invalidated by these three pitfalls.5. It is suggested that the mucin technique be abandoned in the assay of typhoid vaccine.6. A source of error in the rabbit test is the presence of pre-formed Vi agglutinins. These are found in rabbits harbouring coliform organisms which possess the typhoid Vi antigen. Such rabbits do not respond to injections of typhoid Viantigen.7. Standardization of the potency of typhoid vaccine has now become possible. Either an alcohol-preserved or a dried vaccine can serve as ‘standard vaccine’, to be used in combination with the ‘Provisional Standard Anti-typhoid Serum’. Both of these vaccines remain stable for a number of years.8. Suggestions are briefly outlined for:(a) the routine examination in the course of preparation of the vaccine;(b) the official control of the potency of typhoid vaccine.9.The paratyphoid components of T.A.B.C. vaccine can be standardized in an analogous manner.