There are three main types of rabies vaccine:

• Rabies virus phenol- or BPL-inactivated vaccines using as a substrate sheep or goat or brain. It contains nerve tissue and are used in Asia and Africa;
• Rabies virus BPL-inactivated vaccine use as a substrate suckling brain mouse, with a decrease myelin content. It is used in South America.

Avian vaccines using as a substrate duck embryo, are inactivated by b propiolactone, and purification is done by ultracentrifugation. This vaccine is used in Europe.

• Human diploid cell culture vaccine (HDCV) is grown on human fibroblast, inactivated by b propiolactone and mainly used in Europe and USA;
• Primary hamster kidney cells (PHKC) rabies vaccine is grown on hamster kidney cells, inactivated by formalin inactivated; it is produced and used in Russia, some countries in the CIS, and China.
• Purified chick embryo cells culture vaccine (PCEC) is inactivated by b propiolactone purified by ultracentrifugation and has been licensed in Europe for many years and in the US since October 1997;
• Purified Vero rabies vaccine (PVRV) is grown on Vero cells, inactivated by b -propiolactone and purified by ultracentrifugation; licensed in France in 1984.
• Rabies vaccine adsorbed vaccine (RVA) uses a Kissling strain of rabies virus adapted to a diploid cell of fetal rhesus monkey lung fibroblast, inactivated by b -propiolactone, and containing alum phosphate (Plotkin et al., 1999; CDC, 1998).

Vaccines containing animal brain tissues (Wiktor, 1980)

General systemic reactions 

The various minor disorders that may develop during and after a course of antirabies treatment includes fever, headache, insomnia, palpitations, and diarrhoea. Sensitization to proteins contained in older vaccines can cause a sudden shock-like collapse, usually toward the end of the course of treatment.

Local reactions

Erythematous patches may develop approximately 7 to 10 days after the beginning of anti-rabies treatment. Lesions appear on the skin a few hours after administration and fade in 6 to 8 hours, reappearing after the next dose.

Cell-cultured vaccines

Cell-cultured vaccines are widely accepted as well-tolerated rabies vaccines, although reported reaction rates to primary immunization have varied with the monitoring system. In a large-scale testing of the safety and immunogenicity of human diploid cell vaccine performed on American veterinary students, adverse reaction rates observed in more than 1770 volunteers are shown in table 6.

In another study of post-exposure vaccination, 21% had local reactions, 3.6% had fever, 7% had headache, and 5% had nausea. The most common local reactions are erythema, pain and induration (Anderson et al., 1980). A comparative study of HDCV and PVRV vaccines in 144 volunteers did not show serious adverse event with either vaccine, although some vaccinees complained of redness, induration or local pain and exceptionally, fever (Ajjan & Pilet, 1989)

Allergic reactions

Allergic reactions are reported mostly after booster doses of HDCV vaccines (CDC, 1984; Dreesen et al., 1986). The overall incidence was 11 per 10,000 vaccinees (0,11%), but rose to 6% after boosters (Fishbein et al., 1993). These reactions have been attributed to antigenicity conferred on the stabilizer - human albumin - by the b -propiolactone used to inactivate the virus. The b -propiolactone increases the capacity of albumin to form an immune complexes (CDC, 1984; Anderson et al., 1987; Swanson et al., 1987). Respiratory symptoms are mild, there have been no fatalities. Epinephrine, antihistamines and occasionally steroids have been used in successful treatment of these reactions, which have resolved in 2 to 3 days.

Vaccines containing animal brain tissues

Severe and fatal reactions

A patient may suffer from serious and often fatal illness after nerve tissue vaccine. These accidents are of two types: (1) vaccine-induced rabies, a disease induced by the living "fixed virus" present in the Ferme or Pasteur vaccines, and (2) neuroparalytic accidents, which present the greatest danger from rabies vaccination. All types of vaccines containing adult mammalian nervous tissues exhibit similar capacities for inducing neuroparalytic reactions. The neuroparalytic reactions usually develops between the 13^th and the 15^th days of treatment and may assume one of the following three forms:

1. Landry type. In this type of accident, the patient rapidly becomes pyrexial and suffers pain in the back. Flaccid paralysis of legs begins and within one day, the arms become paralyzed. Later, the paralysis spreads to the face, tongue, and other muscles. The fatality rate is about 30%; in the remaining 70%, recovery usually occurs rapidly.
2. Dorsolumbar type. Less severe than Landry type, this is the most common form of neuroparalytic accident. Clinical features are explicable by the presence of dorsolumbar myelitis. The patient may be febrile and feel weak, with paralysis of the lower limbs, diminished sensation and sphincter disturbances. The fatality rate does not exceed 5%.
3. Neuritis type. In this type of accident, the patient may be pyrexial and usually shows a temporary paralysis of the facial, oculomotor, glossopharyngeal or vagus nerves.

Neuroparalytic accidents are caused by allergic "encephalomyelitis", attributable to sensitization to adult nerve tissue antigen (myelin based protein). The incidence of these reactions varies widely from 0.0017% to 0.44% and is definitely lower in people receiving DEV and in people receiving properly manufactured vaccine of newborn rodent brain.

Cell-cultured vaccines

Neurological reactions

Although five cases of central nervous system disease, including transient neuroparlytic illness of Guillain-Barré type, have been reported among the millions of individuals given human diploid cell vaccines (Bernard et al., 1982; Boe & Nyland, 1980; Knittel et al., 1989; Tornatore & Richert, 1990; Moulignier et al., 1991). This rate is too low to be positively related to vaccination, because the background incidence of such diseases is about 1 per 100,000 per year. This low incidence after human diploid cell vaccine compares well with a neurological complication rate of 1:1600 people for nerve tissue vaccine, 1:8000 for suckling mouse brain vaccine and 1:32,000 for duck embryo vaccine.

Ajjan N , Pilet C. Comparative study of the safety and protective value, in pre-exposure use, of rabies vaccine cultivated on human diploid cells (HDCV) and of the new vaccine grown on Vero cells. Vaccine 1989; 7:125-8.

Anderson LJ, Sikes RK, Langkop CE, et al. Post-exposure trial of a human diploid cell strain rabies vaccine. J Infect Dis 1980;14: 133-8.

Anderson MC, Baer H, Frazier DJ, Quinnan JV. The role of specific IgE and b -propiolactone in reactions resulting from booster doses of human diploid cell rabies vaccine. J Allergy Clin Immunol 1987;80:861-8.

Bernard KW, Smith PW, Kader FJ, Moran MJ. Neuroparalytic illness and human diploid cell rabies vaccine. JAMA 1982;248:3136-8.

Boe E, Nyland H. Guillain-Barré syndrome after vaccination with human diploid cell rabies vaccine. Scand J Infect 1980; 12: 231-2.

Center for Disease Control. Advisory Committee on Immunization Practices. Rabies Prevention-United States. MMWR 1984; 33; 393-407.

Center for Disease Control. Systemic allergic reactions following immunization with human diploid cell rabies vaccine. MMWR 1984; 33:185-8.

Centers for Disease Control and Prevention-United States, 1991:recommendations of the Immunization Practices Advisory Committee (ACIP). MMWR 1991;40(No.RR-3):

Centers for Disease Control and Prevention. Availability of new rabies vaccine for human use. MMWR 1998; 47:12-3.

Dreesen DW, Bernard KW, Parker RA , et al. Immune complex-like disease in 23 persons following a booster dose of rabies human diploid cell vaccine. Vaccine 1986; 4:45-9.

Fishbein DB, Yenne KM, Dreesen DW, et al. Risk factors for systemic hypersensitivity reactions after booster vaccinations with human diploid cell rabies vaccine: A nationwide prospective study. Vaccine 1993;14:1390-4.

Knittel T, Ramadori G, Mayet WT et al. Guillain-Barré syndrome and human diploid cell rabies vaccine. Lancet 1989; 1:1334-5.

Moulignier A, Richer A, Fritzell C et al. Méningo-radiculite secondaire à une vaccination antirabique. Presse Med 1991;20:1121-3.

Plotkin SA. Rabies vaccine prepared in human cell cultures: Progress and perspectives. Rev Infect Dis 1980; 2:433-47.

Plotkin SA, Ruppert CE, Koprowski H. Rabies Vaccine. In Plotkin SA, Orenstein WA, eds. (1999). Vaccines (3rd ed.). Philadelphia, PA: WB Saunders Company, pp 743-766.

Swanson MC, Rosanoff E, Furwith M et al. IgE and IgG antibodies to b -propiolactone and human serum albumin associated with urticarial reactions to rabies vaccine. J Infect Dis 1987; 155: 909-13.

Tornatore C, Richert A. CNS demyelination associated with diploid cell rabies vaccine. Lancet 1990; 335:1346-7.