▶Oshida Vaccine（Tokyo Research Institute for Microbiology）
Production method: (for humans and animals) Rabbit cerebrospinal fluid is made into a 10-fold emulsion with coal acid (0.5%) glycerin (66%) or coal acid saline (0.85%), filtered, and decontaminated at 37°C for 2 days.
Price: ¥6.50 per 100 cc
In 1915, a method was reported in which a fixed poison infected rabbit cerebrospinal emulsion was diluted 4 times with 0.5% glycerol coalate solution, sensitized in a refrigerator for 1~1.5 months, diluted 5 times at the time of use, and injected subcutaneously 10~15 times into dogs as a vaccine. The concentrated fixed poison emulsion used for humans was also inoculated into dogs, cats, dairy cattle, and horses to verify its efficacy. In all cases, it was shown that inoculation at the appropriate time, frequency, and dose after infection is received is sufficient to prevent disease onset.
He also examined inactivated vaccines and recommended the use of the dry method instead of the dilution method as a method of decontamination. Specifically, first inoculate rabbits with diluted fixed venom, collect the cerebrospinal cord, place it in a drying container, and keep it in a refrigerator to dry. In 1953, he developed a dry powdered rabies inactivated vaccine for animals (S.G.R.V.) and conducted various studies to realize mass vaccination against rabies.
Umeno Vaccine（Kitazato Research Institute）
Production method: Rabbit cerebrospinal fluid is made into a 6-fold emulsion with coal acid (0.5%) and glycerin (60%), filtered, and left at room temperature for 10 days in summer and 14 days in winter to reduce the amount of poison.
Price: 2.80 yen per 30 cc
In 1916, Nobukichi Umeno reported on his research to simplify the rabies vaccination method developed by Pasteur. Using glycerin-coal acid water diluted fixed poison as the inoculation material, he clarified its high shelf life at room temperature, and also studied the number of inoculations, the amount of intake, and the inoculation method. In 1918, following the first report, he published a study on a simpler and more reliable method of rabies inoculation. Experiments were conducted on the number of inoculations, inoculation dose, and inoculation site for pre-exposure inoculation and post-exposure inoculation after corneal surface inoculation, showing that the vaccine does not need two dilutions (20x dilution) but only one dilution (5x dilution), that one or two inoculations are sufficient to show efficacy, and that a certain efficacy can be expected even with post-exposure inoculation. The results of the study showed that the vaccine is not required to be diluted in two steps (20x dilution) and can be diluted once (5x dilution).
▶Kondo Vaccine（Quarantine station / Institute for Infectious Diseases）
Production method:
(For humans) Make a 5-fold emulsion of canine cerebrospinal cord with coal acid (0.5%) and glycerin (50%), filter, and decontaminate at 37°C for 3 days.
(For animals) Leave the diluted solution of rabbit fixed poison at 20°C for 6 days to decontaminate.
Price: (for humans) 7.50 yen per 100 cc / (for animals) 30.0 yen per 250 cc
The Nishigahara strain with the shortest incubation period in the literature was established in 1918 at the Veterinary Quarantine Research Station after receiving the Pasteur rabies virus strain. Using this strain, a vaccine was developed using dog cerebrospinal cord as the source of material, and was made by heating and decontaminating the material according to the method of Umeno et al. This vaccine was characterized by its low side effects and low production cost because it was manufactured using dogs.
Significance of the Development of “Japanese Method”
At the International Rabies Conference held in Genoa in 1927, the dilute emulsion one-dose vaccination method using coal acid and glycerin water, which had been used in the Umeno and Kondo methods, was approved as the “Japanese method”. The main features of this method were the low frequency of injections and the simplicity of the vaccine production process.
The fact that dogs could be immunized with a single injection meant that the radical rabies prevention strategy of preventing the spread of rabies by injecting dogs with the vaccine became a reality. In Japan, the number of dogs vaccinated against rabies increased from 1918~1920. In Japan, about 3 million dogs were injected during the 30 years from 1918 to 1948, and only 410 dogs (0.014%) developed rabies. On the other hand, 19,306 rabies cases were reported in non-injected dogs (mainly wild dogs).
(Figure) Number of dogs vaccinated against rabies in Tokyo during 1916-1929