042 - Rabies Vaccine Protection Tests

When studying rabies vaccines (or any vaccine, I expect) in animals, it is important to challenge the animal subjects with the pathogen in such a way as can reliably infect all of them, without being so much exposure that it overwhelms any immunity or other defenses they might have (and is way more than they would encounter outside the lab anyway).

The challenge is known as the infectious dose, and people were having trouble getting it right with rabies at that time. Since the rabies virus travels slowly but inevitably (in non-immune animals) up the nerves to the brain, the location of infection is important; farther from the brain will give the animal a better chance of developing immunity before the virus becomes fatal. So the question for researchers was where to inoculate: too far away and the animals would often survive; too close and they would die.

Reichel and Schneider, in today's study, proposed a solution: the tongue. They tried it on a number of rabbits after anesthetizing them, and it seemed to work well without bothering the animals much. Compared to injection into the cranium, injection into the tongue gave the animals a couple extra days before they showed symptoms.

So they tried a protection test of a couple vaccines, prepared different ways; in one, they used chloroform to deactivate the virus, and in the other, they used phenol. Both protected all 8 rabbits tested from infection, while 80% of the 5 controls died (one survived somehow, as some older rabbits occasionally did, possibly because the virus was not as virulent as it could've been).

Then they wanted to test the vaccines' shelf life; they had some of different ages, up to a few years old, that had been sitting at room temperature. The two oldest batches didn't protect any of the test animals; they were expired. The third oldest protected 75% of rabbits, and the newest 100%. 83% of the control animals died. Just to see, they tried "vaccinating" with brain tissue not containing any virus, and that didn't protect rabbits either, obviously.

Lastly, they tried testing the minimum effective dose, and the immunity duration (how long before a vaccinated rabbit lost its immunity). So they gave three rabbits four small doses of vaccine, then challenged them; all died.

Then they gave three more rabbits seven small doses, and two survived when challenged with rabies. The third died of a broken back, seemingly not connected with its infection at all, so it could be said to be a 100% protection rate. Reichel and Schneider challenged the surviving rabbits again with rabies after half a year, though, and both died. So the immunity from that dose waned after less than half a year.

The third group of three got 14 small doses. All of them survived the first challenge, and they also survived the second, half a year later. The last challenge, a year after vaccination, killed one of the three. So immunity may have waned partially after a year, at least in one of them.

The controls for each of these three challenges mostly died, by the way.

These were pretty small groups of animals, so the conclusions that can be drawn aren't huge, but the vaccines seem to work, at least for a while, and the methods seem effective, and the point of the paper was to test the methods, so good job I suppose. If anything, you could say that the preparation methods tested didn't differ much, that vaccine older than 2 years is expired, and that a course of 14 small vaccinations protects most for at least a year.

Citation: Reichel, J. & Schneider, J. E. Rabies Vaccine Protection Tests. Am J Public Health Nations Health 24, 625–628 (1934).