023 - Studies on Experimental Pneumonia IV. Results of Prophylactic Vaccination Against Pneumococcus Pneumonia in Monkeys

Disappointed by previous ambiguous results (here and here), Russell Cecil and colleagues decided to refine their attempts using model animals—Philippine monkeys, in this case. These animals show symptoms similar to those in humans when infected with pneumococcus, so it seemed like they would make a good model organism.

In a series of small experiments, the authors tried out different doses, types of vaccine, and routes of infection. Most of them had up to only 3 vaccinated monkeys (often with different doses of vaccine and/or infectious bacteria) and up to 3 controls. They tried making vaccines with bacteria suspended in vegetable oil or in salt solution; they tried high doses (the same amount as would be given to an adult man) or lower doses (like a human dose but proportional to the monkey's weight); and they tried infection by squirting pneumococcus into the monkeys' airways, or by putting them in a cage with other infected monkeys, or by injecting bacteria directly into the blood.

Overall, the results were disappointing: when exposed to bacteria by aerosol, almost all of the monkeys, vaccinated or not, got pneumonia. 42% of the vaccinated died, compared to 76% of the controls (that's something, at least, but not great at all). They tried testing for antibodies, but rarely found any.

The authors speculated about why the vaccine worked so poorly: possibly the dose was incorrect, or the strain used for infection was too virulent and overcame any immunity, or the monkeys were just too susceptible to pneumococcus. They pointed out that others had tried testing in apes the typhoid vaccine (so successful already in humans), and found no protection, so maybe monkeys aren't such a great model.

The one good and interesting result they got in this study was the observation that, when they vaccinated monkeys and infected them by infection directly into the bloodstream, they seemed to be protected much more effectively than when infected by aerosol. The two vaccinated monkeys survived with hardly any symptoms, while the one control died quickly. This fit in with results of the earlier experiments showing relatively sterile blood in the vaccinated monkeys (who nonetheless still suffered lung infections). The implication is that there is a distinction between humoral (that is, bloodstream-based) immunity and immunity in the lung (mucosal, perhaps?), and one did not necessarily translate into the other. That's an interesting observation, one worth considering in other experiments in which subjects may be exposed to infection via a route that doesn't accurately represent the normal route. On the other hand, there were only three subjects, so maybe it's meaningless. Too soon to say.

Citation: Cecil, R. L. & Blake, F. G. Studies on Experimental Pneumonia IV. Results of Prophylactic Vaccination Against Pneumococcus Pneumonia in Monkeys. J Exp Med 31, 519–553 (1920).