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Field Trial of Shigella Flexneri III Vaccine

VI. Mouse Protective Studies^1,2,

From the Naval Medical Research Institute, Bethesda, Maryland and the Children's Hospital Research Foundation, Cincinnati, Ohio

Abstract

1. Mouse protective tests were conducted with serums taken from 633 officers and men aboard five cruisers before inoculation with Shigella flexneri III vaccines and from different groups at eight postinoculation intervals; a control group that received placebos only was included. Statistical evaluations of the data were made to obtain evidence concerning the efficacy of the vaccines employed.

2. Statistically significant antibody responses were observed in serums from two groups of men who had received primary subcutaneous inoculations of S. flexneri III vaccine; fold increases were 9.2 and 10.5. Little or no enhancement in protective power of serums was obtained by oral administration of S. flexneri III vaccine.

3. The peak of protective antibody production following parenteral inoculations was reached approximately three weeks after the last injection in the initial course of vaccine. Evidence was obtained that indicated the persistence of a statistically significant amount of circulating antibody for approximately six months.

4. Previous epidemiologic experiences of men with S. flexneri III apparently influenced their antibody response to artificial parenteral stimulation with vaccine. Preinoculation antibody levels differed significantly depending upon whether individuals had been present and ill, present but not ill, or not present in an epidemic. Those who had reported clinical symptoms possessed the highest titers and serums from men with no prior contact showed the lowest antibody content. Protective antibody levels after inoculation were, however, of a similar order in the three groups. It appeared, therefore, that there was a point beyond which antibody formation could not be increased by the stimulus applied regardless of the initial antibody level.

5. A single subcutaneous booster dose of S. flexneri III vaccine administered to a group of men six months after the initial inoculations increased only slightly the mouse protective power of the serums. This lack of further antibody response following the recall dose was probably due to the persistence of antibody levels that could not be elevated markedly by the additional antigen injected.

6. It appeared that the parenterally administered S. flexneri III vaccine induced the production of protective antibody in susceptible individuals to a degree comparable with that found in men who had experienced a natural infection. Records suggest that persons who have convalesced from the disease rarely suffer second attacks due to the same Shigella type.

Footnotes

¹ The opinions expressed are those of the authors and do not necessarily reflect those of the Navy Department or the naval service at large.

² That portion of the investigations made at The Children's Hospital Research Foundation was conducted under a grant-in-aid from the U. S. Public Health Service.