Controlled field trials of killed oral typhoid and paratyphoid B vaccines and cell-free, chemical aerosol typhoid vaccine.

Three controlled field trials were carried out. One of them (1963) showed that an aerosol with cell-free, chemical typhoid vaccine did not protect vaccinees from the disease. The other trials (1964 and 1965) assessing the efficacy of killed oral typhoid vaccine revealed a short term (up to 3 months) protective effect. In the trial of oral paratyphoid B vaccine no statistically significant difference in morbidity in the test and control groups was observed due to the small number of cases.

Controlled field trial with dried sorbed paratyphoid B and typhoid vaccines.

In 1968-70 a field trial was arranged in the USSR to evaluate the effectiveness of dried sorbed paratyphoid B and typhoid vaccines when administered in two doses separated by an interval of 20-30 days.TWO GROUPS OF SCHOOLCHILDREN WERE UNDER OBSERVATION: a group inoculated with paratyphoid B vaccine (75 805 children) and a group inoculated with typhoid vaccine (76 314 children). The persons who were inoculated with the paratyphoid B vaccine formed the control group used in evaluating the effectiveness of the typhoid vaccine, and those inoculated with the typhoid vaccine formed the control group for the evaluation of the paratyphoid vaccine.Two doses of dried sorbed paratyphoid B vaccine made from Salmonella paratyphi B, strain No. 42, containing 5 x 10(8) microbial cells per injection, protected about 70% of those inoculated. Two doses of dried sorbed typhoid vaccine made from S. typhi, strain Ty 2 4446, also with 5 x 10(8) cells per injection, protected about 80% of those inoculated.At least 21 months of protection (the period of observation) were obtained following immunization with dried sorbed preparations made from heat-killed aerated broth cultures.Both types of vaccine produced the same frequency and intensity of general and local reactions; these were moderate. The general and local reactions to a second injection were substantially less marked than those to the first.

Laboratory characteristics of paratyphoid B vaccines tested in controlled field trials.

The immunization of human beings with paratyphoid B vaccines, in doses producing a marked protective effect in field trials, resulted in H-agglutinin titers that were significantly higher than those produced by ineffective doses. In immunization of rabbits and white mice, the same difference in doses had a significant effect on the ability of vaccines to stimulate the formation of H and O antibodies. A parallel was noted between the effectiveness of vaccine for human beings and the activity of sera of the corresponding group of people in the passive mouse-protection test, with a correlation between such activity of sera and the 19S O-hemagglutinin titers. The data obtained suggested as promising the determination of agglutinin dynamics in the sera of inoculated human beings and animals to evaluate the antigenic activity of paratyphoid B vaccines in the laboratory. The passive mouse-protection test with human sera holds promise for laboratory evaluation of the effectiveness of paratyphoid B vaccines. At the same time, none of the variation of the active mouse-protection test employed permitted a significant difference to be detected between the vaccines effective and ineffective for man. Comparison of data on the frequency and degree of febrile vaccine reactions in man with results of laboratory evaluation of vaccine toxicity showed that, provided a reference vaccine with known pyrogenic capacity for man was employed, the study of stress effect of vaccines on guinea-pigs (determination of 17-oxycorticosteroid content) may permit prediction of the reactive power of the vaccine. No correlation was found between the pyrogenic capacity of vaccines for man and their toxicity for mice.

A controlled field trial to evaluate the protective capacity of a single dose of acetone-killed agar-grown and heat-killed broth-grown typhoid vaccines.

In a strictly controlled field trial among schoolchildren a study was made of the protective capacity of single doses of 2 typhoid vaccines: a heat-killed broth-grown sorbed dried vaccine made in the USSR (vaccine G-66) and an acetone-killed agar-grown dried vaccine (vaccine K-66) made in Yugoslavia. The latter vaccine was supplied by the World Health Organization.A single dose of these preparations exerted a statistically significant protective effect during the first 10 months of observation. The protection afforded by the acetone-killed and heat-killed sorbed vaccines was similar in duration and intensity to that resulting from single doses of other types of typhoid vaccines that had been evaluated earlier in the USSR. The data obtained confirm once again that successful immunization against typhoid is possible with a single dose of vaccine.The absence of any substantial difference in morbidity between the groups concerned indicates that the heat-killed broth-grown and acetone-killed agar-grown vaccines exert a roughly similar protective effect.

Controlled field trials of paratyphoid B vaccine and evaluation of the effectiveness of a single administration of typhoid vaccine.

In 1963 and 1964 field trials were organized in the USSR for the purpose of evaluating the effectiveness of paratyphoid B vaccine. An opportunity was thereby afforded to assess the effectiveness of a single administration of typhoid vaccine, used as the preparation administered to the paratyphoid control group of 89 046 persons. Similarly, the control group used for assessing the effectiveness of the typhoid vaccine was the group of 86 620 persons inoculated with the paratyphoid vaccine.It was established that it is, in principle, possible to immunize people effectively against paratyphoid B by administering heat-killed paratyphoid B vaccine prepared from an aerated broth culture. It was found that the protective effect of the vaccine depends upon the size of the dose and the number of times it is administered. A protective effect was produced when a dose of 6 x 10(8) organisms was administered to persons from 7 to 16 years of age. Two inoculations of the paratyphoid B vaccine ensured protection over the 30 months that the observations lasted, whereas a single administration only conferred protection for up to one year.It was also confirmed that it is possible to obtain a protective effect with a single administration of a heat-killed typhoid vaccine prepared from an aerated broth culture. A single administration of the typhoid vaccine had a less marked protective effect (index of effectiveness 58%) than 2 administrations, a fall in the level of the protection conferred occurring during the year after immunization. The frequency and intensity of general and local reactions were identical for equal doses of typhoid and paratyphoid B vaccine.

A controlled field trial and laboratory study of five typhoid vaccines in the USSR.

A controlled field trial of typhoid vaccines was carried out in the USSR in 1962. It was the fifth and last of a series. Five preparations were tested, the most effective being a heat-killed divalent vaccine prepared from aerated broth culture. The results of a laboratory study of the vaccines were not in complete agreement with the data from the field trial. No correlation was found between the effectiveness of vaccines and the data from laboratory tests as to their potency, and the authors suggest that differences in effectiveness may be due to varying degrees of damage to biological components during the different production processes. The effectiveness is also sensitive to dosage.