007 - Chemical Vaccine against Rabies

Finally we get to something besides smallpox. These researchers in 1893 claim to have extracted material from the central nervous system (CNS) of animals dead from "fixed" rabies (that is, a strain of virus that had been maintained in lab animals) and used this to vaccinate rabbits against the disease. Supposedly when they injected as much as 5 grams of this material in 50 milliliters of liquid under the rabbits' skin, it didn't cause any irritation or side effects at all.

They did some experimental trials with this vaccine too. The first consisted of 14 vaccinated and 6 control rabbits. The former were injected with the vaccine in various quantities between two weeks and one day before being exposed to and infected with "street" rabies (which I assume means the kind you find on the street, that is generally deadly). All of the controls died of the rabies within 21 days, but twelve of the vaccinated rabbits lived at least 5 months (up to the time the study was published, and probably longer) without illness. The two vaccinated that did die of rabies had been given the smallest amounts of vaccine material. But even the one vaccinated right before being infected survived just fine.

This observation probably led to their next trial: vaccinating the rabbits after infecting them with rabies. There were 6 vaccinated and 5 controls in this experiment. The former were vaccinated between 14 hours and 7 days after being infected with "street" rabies. As before, the controls died within 20 days. But four of the six vaccinated did not get sick; the two that did had received either a smaller amount 30 hours after infection, or hadn't been vaccinated until day 7. So vaccinating against rabies works even after being infected with the disease, but it takes more vaccine material and has to be done within a certain incubation period.

These are pretty exciting results. I think if this were a study done today, I wouldn't count it as worth very much (small numbers, only done in animals, probably no blinding), but it seems good for the time, and definitely worth further investigation.

The authors conclude from the lack of side effects and absence of any observable life forms in the extracted vaccine material that the vaccine is chemical in nature, not infective. I don't think viruses had been discovered yet (not until 1898).

It does raise some questions for me though, which would probably be answered if I knew more about rabies. One is, why doesn't the CNS material—taken from animals that died from rabies—cause rabies itself? Maybe the virus dies soon after the animal dies, and then its remnants can be used as a vaccine. How long does the immunity last? Modern pet rabies vaccines require boosters every 2-3 years, but that's still better than nothing. I expect to learn more as I continue to read.

Citation: Tizzoni & Centanni, E. Chemical Vaccine against Rabies. Br Med J 1, 516–517 (1893).