Rabies Pre-Exposure Prophylaxis
Primary Vaccination Regimen
The standard pre-exposure prophylaxis consists of three 1.0-mL intramuscular injections of either human diploid cell vaccine (HDCV) or purified chick embryo cell vaccine (PCECV) administered in the deltoid area on days 0,7, and 21 or 28. 1, 2
- This three-dose series establishes adequate immunity and creates immunologic memory for future exposures, with antibody detected in all subjects when tested by rapid fluorescent focus inhibition test (RFFIT). 1, 2
- The timing is critical: first dose on day 0, second dose on day 7, and third dose on either day 21 or day 28. 1, 2
Who Should Receive Pre-Exposure Prophylaxis
High-risk individuals who should receive pre-exposure vaccination include: 1, 2
- Veterinarians and their staff 1, 2
- Animal handlers and animal control officers 1, 2
- Laboratory workers handling rabies virus 1, 2
- Rabies researchers and diagnosticians 1, 2
- Individuals who frequently handle bats (spelunkers/cavers) 2
- International travelers to rabies-endemic areas with limited access to post-exposure prophylaxis 1, 2
Key Benefits of Pre-Exposure Prophylaxis
Pre-exposure vaccination provides three critical advantages: 1, 2
- Eliminates the need for rabies immune globulin (RIG) after exposure, which is often unavailable or expensive in resource-limited settings. 1, 2
- Reduces post-exposure vaccine doses from 4 to only 2 doses (given on days 0 and 3). 2, 3
- Provides protection if post-exposure treatment is delayed or against unrecognized exposures. 1, 2
Booster Dose Strategy Based on Risk Category
Continuous Risk Category (Laboratory Workers)
- Test serum for rabies antibody every 6 months. 1, 2
- Administer booster if titer falls below complete neutralization at 1:5 serum dilution by RFFIT. 1, 2
Frequent Risk Category (Veterinarians, Diagnostic Lab Workers, Animal Control Officers in Endemic Areas)
- Test serum for rabies antibody every 2 years. 1, 2
- Administer booster if titer is less than complete neutralization at 1:5 serum dilution by RFFIT. 1, 2
Infrequent Risk Category (Veterinarians in Low-Rabies Areas, Travelers)
- No routine booster doses required after completing primary series. 1
Important note: Recent research suggests that a single systematic booster after primary vaccination may provide long-term immunity in nearly all individuals (99.5% adequate response), potentially alleviating the need for frequent antibody monitoring. 4
Post-Exposure Management for Previously Vaccinated Persons
If a previously vaccinated person is exposed to rabies, give only 2 intramuscular doses of vaccine (1.0 mL each) on days 0 and 3, without RIG. 1, 2, 3
- Previously vaccinated persons are those who completed any recommended pre-exposure or post-exposure regimen with cell culture vaccine or had documented rabies antibody titer. 1
- RIG is contraindicated in previously vaccinated persons because it will inhibit the anamnestic antibody response. 5, 3
Special Considerations and Pitfalls
Immunocompromised Patients
- Postpone pre-exposure vaccination when possible. 2
- If vaccination cannot be postponed, check antibody response after completing the series. 2
Antimalarial Drug Interactions (Historical Note)
- Chloroquine phosphate and structurally related antimalarials (e.g., mefloquine) may decrease antibody response to HDCV. 1
- If both rabies prophylaxis and antimalarial chemoprophylaxis are needed, use the intramuscular regimen (not intradermal) to provide sufficient margin of safety. 1
- Note: Intradermal pre-exposure prophylaxis is no longer available or recommended in the United States. 1
Vaccine Products No Longer Available
- Rabies vaccine adsorbed (RVA) is no longer available in the United States. 1
- Only HDCV and PCECV are currently approved for intramuscular pre-exposure prophylaxis. 1, 2