New Rabies Vaccine Available in the United States
VACCINE UPDATE
By Michele Barry, MD
Rabies is one the oldest recorded infections of mankind. The word rabies comes from the Sanskrit word "rabbahs" which translated means "to do violence." The Greeks were familiar with the disease, and, in Homer's Iliad, Hector is defamed by the appellation "mad dog." Girolamo Fracastoro (1478-1553) strongly emphasized that rabies transmission required more than simple contact, but also tearing of the outer skin by the bite of a rabid dog which draws blood. The first rabies vaccine was developed by Pasteur in 1885. Pasteur successfully administered a "post-exposure" vaccination series to 9-year-old Joseph Meister, who received his exposure from a dog bite. Over the next 50 years, various modifications to Pasteur's crude desiccated nerve tissue vaccine took place and improved both safety and efficacy.
The virus was grown in various animals and inactivated using ultraviolet light or phenol. Vaccines of this type using sheep or goat brains (Semple) and suckling mouse brain are still in use in many developing countries and have been unfortunately associated with demyelinating central or peripheral nervous system side effects in from 1/3000 to 1/7000 persons vaccinated. In the 1950s, embryonated tissue vaccines came on the market. Vaccines such as the duck embryo vaccine (DEV) were used extensively for about 25 years in the United States until the 1980s. The vaccine induced a poor antigenic response and often caused severe adverse reactions. Cell culture vaccines or the development of human diploid cell vaccines (HDCV) were pioneered by Hilary Koprowski, MD, and his colleagues at the Wistar Institute, Philadelphia. Today, many of the derivatives of tissue culture vaccines are similar to HDCV and are well tolerated and effective. They include purified chicken embryo cell vaccine, the purified Vero cell rabies vaccine (PVRV), and a purified duck embryo cell vaccine (PDEV), which is far safer than its predecessor. Russia and China manufacture primary hamster kidney cell vaccine (PHKV) which is of lower potency and, therefore, often contains adjuvants. Because of the expense of cell culture rabies vaccines, the availability (see Table) is often lacking in developing countries that have high rates of circulating rabies virus.
Table
Worldwide Use of Cell Culture Rabies Vaccines
Western Europe 100%
North America 100%
Middle East 70%
Southeast Asia 70%
Africa 20%
Latin America 20%
Western Pacific 20%
Despite the development of safe, effective vaccines, there are still more than 40,000 deaths from rabies annually worldwide.
New Vaccine Available in the United States
The FDA recently approved for marketing a new inactivated rabies vaccine (RabAvert, Chiron Corp.) that is grown in primary cultures of chicken fibroblasts. It is the first new vaccine against rabies to be introduced in almost 10 years and has been approved for both pre-exposure prophylaxis and post-exposure vaccination. It has been used in more than 16 million doses in 29 countries since 1985, and, among patients who received post-exposure prophylaxis in compliance with WHO guidelines, none developed rabies. RabAvert has proven effective in boosting titers to individuals who were previously immunized with human diploid vaccine (although the manufacturer is recommending continuing booster regimens with same vaccine used for initial series). Of interest, RabAvert has not induced type III hypersensitivity in individuals who needed a booster vaccination and were previously immunized by RabAvert or HDVC. The new vaccine is being marketed only as an intramuscular preparation with a 1 cc dose costing the pharmacy approximately $160. (Dr. Barry is Professor of Medicine, Co-Director, Tropical Medicine and International Travelers' Clinic, Yale University School of Medicine.)
References
1. Dressen D. A global review of rabies vaccines for human use. Vaccine 1997;15 (Suppl):S2-6.
2. Fu ZF. Rabies and rabies research: Past, present and future. Vaccine 1997;15 (Suppl):S20-24.
3. John TJ. An ethical dilemma in rabies immunization. Vaccine 1997;15 (Suppl):S12-15.
4. Lontai I. The current state of rabies prevention in Europe. Vaccine 1997;15 (Suppl):S16-19.
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