Human Rabies Vaccines

Vaccination has been an integral part of rabies prevention since 1885 when Pasteur first successfully immunized a 9-year-old boy bitten by a rabid dog. Until two decades ago, however, the human vaccines in use had relatively low purity and potency. A difficult vaccination schedule of 14–21 inoculations with two booster doses was required for post-exposure treatments. In addition, adverse reactions during vaccination were common. Since 1980, cell culture-derived vaccines with greater immunogenicity have been used in this country. These vaccines have proved to be safe and effective when administered correctly.

Currently Available Vaccines

Three human rabies vaccines are currently available in the United States: human diploid cell vaccine (HDCV); rabies vaccine adsorbed (RVA); and as of late 1997, purified chick embryo cell culture vaccine (PCECV). All three vaccines can be given before an exposure occurs (pre-exposure vaccination), as well as after a person is bitten or otherwise exposed to a rabid animal (post-exposure vaccination).

Interchangeability of Vaccines

Whenever possible, the vaccine from a single manufacturer should be used to complete a series; however, HDCV and RVA are interchangeable when used as recommended. Although the experience with PCECV is more limited, booster doses of this vaccine appear to elicit a satisfactory immune response in persons previously vaccinated with HDCV. In addition, persons immunized with duck embryo vaccine respond appropriately to booster doses of HDCV and RVA.

Adverse Effects of Rabies Vaccines

HDCV: Anaphylactic reactions have been reported but appear to be very rare. Local reactions (pain, redness, swelling, or itching) are reported by 25% of HDCV recipients. Mild systemic symptoms occur in about 20% of recipients. An immune complex-like reaction (characterized by urticaria, and sometimes including arthralgia, arthritis, angioedema, nausea, vomiting, fever, and malaise) occurs in approximately 6% of persons receiving booster doses of HDCV. This reaction is much less common in persons undergoing primary immunization. In no cases have the illnesses been life-threatening. Three cases of a post-vaccination transient illness resembling Guillain-Barre syndrome have been reported. All three resolved without sequelae.

RVA: Anaphylactic reactions have not been reported. Local reactions occur in 65–70% of RVA recipients. Up to 10% of recipients report mild systemic symptoms. Fewer than 1% develop an immune complex-like illness. No serious neurologic conditions have been reported following RVA administration.

PCECV: PCECV has been used extensively in other countries. Approximately 11.8 million doses have been distributed worldwide. Two instances of anaphylaxis have been reported. PCECV is derived from eggs and should not be administered to people with egg allergies. Local and mild systemic reactions appear to be less common than with HDCV. No immune complex-like illnesses have been reported. Serious neurologic complications have been reported in 21 recipients of this vaccine.

Use in pregnancy

Although animal reproductive studies have not been conducted with these vaccines, no fetal abnormalities have been attributed to use of HDCV, RVA, or PCECV. If vaccine is indicated during pregnancy, it should be given.

Drug Interactions

Immunosuppressive agents (including corticosteroids) can interfere with the development of antibodies following vaccination and should not be administered during post-exposure therapy unless essential for the treatment of other conditions. Antimalarials (such as chloroquine phosphate and mefloquine) can also interfere somewhat with the response to rabies vaccines. Vaccine should only be administered by the IM route in persons receiving these drugs.

When to Check Post-vaccination Titers

Persons who may be immunosuppressed (either by disease or medications) should have post-vaccination antibody titers checked to determine if adequate protection has developed. The standard test is the Rapid Fluorescent Focus Inhibition Test (RFFIT), which is currently done routinely at several laboratories. Each laboratory will provide details on how to collect and submit specimens. For questions about emergency serologic testing, contact the Communicable Disease Epidemiology Section at 206.361.2914 or toll-free at 1.877.539.4344.

Laboratories Providing Rabies Titer Testing to the General Public

Historical note and disclaimer