056 - Immunological Studies in Tuberculosis VI. Resistance of Guinea Pigs Vaccinated with Bacillus Calmette-Guérin (BCG)

Today's topic: tuberculosis. This study's authors, Petroff and Steenken, Jr., think that recent (at that time) studies of TB vaccines, especially the BCG live attenuated kind, were too inconsistent and conflicting, possibly because they were done on humans for short periods of time. What they wanted was long-term animal studies. This seems like a controversial opinion, since animals aren't always good models, but they went with it.

Petroff and Steenken Jr. felt that the safety of BCG had already been established, so their goal here was to test its efficacy in preventing tuberculosis, and determine the best dose, route of inoculation, etc.

To do this, they did four experiments with groups of guinea pigs, inoculating them with live BCG or another attenuated strain called R₁ or a strain called H₃₇ killed with heat, or nothing (as a control). The inoculations in the first three experiments were either intraperitoneal (in the abdomen) or subcutaneous, and the scientists tested the immune response by seeing if the animals' skin was hypersensitive to TB proteins. Then, after 4-5 weeks, they infected the animals with live, virulent H₃₇ tuberculosis.

Over the course of 516 to 619 days, they looked at the extent of disease among the guinea pigs, as well as average survival time (though this was complicated by some animals dying of other diseases). In terms of extent of disease, it didn't seem like any of the vaccines was especially better than the others, but all seemed to help somewhat (control animals consistently died after 220-230 days, while vaccinated often lived more than 300). R₁ might've been slightly better than the others.

The fourth experiment was somewhat different: instead of using adult animals vaccinated by injection, they tested the recommendation of Calmette (the discoverer of BCG) of feeding the vaccine to very young guinea pigs. This didn't work out well; neither BCG nor heat-killed vaccine induced a hypersensitive response, and neither seemed to protect the animals against TB.

Not too great a study, but it shows some effect at least.

Citation: Petroff, S. A. & Steenken, Jr., W. Immunological Studies in Tuberculosis VI. Resistance of Guinea Pigs Vaccinated with Bacillus Calmette-Guérin (BCG). J Immunol 19, 79–92 (1930).