052 - Vaccination Against Tuberculosis. Comparative Results Obtained with Koch's Bacillen Emulsion, Calmette's B.C.G., and the Caseous Vaccine of the Saranac Laboratory

BCG seems like a good option for vaccinating against tuberculosis, but not everyone was comfortable being injected with live, potentially pathogenic organisms. Especially people in the US and UK. So Hugh Kinghorn and Morris Dworski tried to develop another type of vaccine that was equivalent but more appealing, using killed bacteria.

They based their strategy, as far as I can understand, on the observation that tuberculosis often produces lesions in the lung full of caseous material, which probably also includes products of the pathogen that are harmful to the tissues, so incorporating this material into a vaccine could help protect both against the pathogen itself and its harmful products. They call this the "caseous vaccine."

So then they set off to test this new vaccine in rabbits and guinea pigs. In the first set of experiments, the caseous vaccine did much better than no vaccine at all protecting the animals, and even did better than Robert Koch's attempt to make a TB vaccine. In one group of animals receiving the caseous vaccine, 75% had no disease at all and the other 25% only had mild TB.

In another experiment with just the caseous and negative controls, 35% of the vaccinated had no disease (compared to 26% of the controls), while only 46% of the vaccinated and 74% of the controls had advanced tuberculosis. Kinghorn and Dworski speculated that the controls did so well because their living conditions were good.

Lastly, they compared their caseous vaccine to the BCG version in rabbits. Three groups of 15 animals each got the caseous, the BCG, or none. 89% of those receiving the caseous were protected from TB, compared to 78% from the BCG and 10% from neither. No animals from either vaccinated group had advanced TB, whereas 40% of the controls did. The rest had mild disease.

After about 1.5 years, they re-infected the surviving rabbits from this experiment with TB, to test if the immunity from the vaccines lasted that long. This time, only 17% that got the caseous, 50% that got the BCG, and 20% of the controls had no disease; 17% each of caseous and BCG groups had advanced disease, and 80% of the controls.

They also looked at whether BCG on its own, since it is a live organism, caused disease at all. But they only saw a couple mild lesions on a couple animals, and no other symptoms.

So it seemed like the caseous worked pretty well at first, but didn't last very long compared to the BCG. And neither is super-great, so the authors recommend not relying on the vaccine as the only preventative measure, which seems wise.

From this study, the caseous vaccine does seem potentially useful especially for people who are nervous about attenuated vaccines, but no future papers have cited this study and I've never heard of caseous vaccines, so it might be only a historical curiosity at this point. There's some pretty good animal data about the BCG here though.

Citation: Kinghorn, H. M. & Dworski, M. Vaccination Against Tuberculosis. Comparative Results Obtained with Koch’s Bacillen Emulsion, Calmette’s B.C.G., and the Caseous Vaccine of the Saranac Laboratory. Trans Am Clin Climatol Assoc 53, 1–14 (1937).