Tuesday, March 18, 2008

Challenges and novel trends in rabies post-exposure prophylaxis (PEP)

Richard Franka, Xianfu Wu, Boonlert Lumlertdacha, and Charles E. Rupprecht. NCZVED/DVRD/PRB/Rabies, CDC, 1600 Clifton Road, Atlanta, GA, USA

Learning Objectives for this Presentation:

Rabies is an inevitably fatal, but preventable disease. More than 55 000 people die every year from rabies in developing countries largely due to the unavailability of affordable effective biologicals.

The aim of our study was to compare protection elicited by PEP against rabies virus infection using inactivated and attenuated vaccines and to evaluate the efficiency of newly developed cocktails of monoclonal antibodies.

Two months old hamsters were inoculated into the gastrocnemius muscle with dog/coyote rabies virus. The experimental PEP was initiated 1, 3, 5 or 7 days post exposure (p.e.) Animals were divided into groups with different PEP schedules and biologicals used. Inactivated or reverse genetic attenuated-live ERAG333 or ERA2G333 vaccines were administered intramuscularly as one or multiple doses alone or in combination with human or horsevimmune globulin, F(ab)2 fragments or cocktails of monoclonal antibodies. Survivorship was observed.

All hamsters succumbed if only inactivated vaccine was used or if ERAG333 or ERA2G333 were given 7 days p.e. However, 50% of animals survived when PEP with one dose of ERA2G333 was started 1 or 3 days p.e. Similarly, 17%, 33% and 83% hamsters survived when PEP was initiated with ERAG333 on day 5, 3 and 1 p.e., respectively. All animals succumbed when standard PEP with an immune globulin and inactivated vaccine was initiated at day 3 or later.

Highly attenuated ERA viruses, used as PEP alone in one dose, provided protection even when the initiation of PEP was delayed by 3-5 days. An immune globulin and inactivated vaccine failed to elicit immune responses able to clear rabies virus, once sequestered in the CNS. Clearly, the earliest possible PEP initiation after exposure is critical for success. Cocktail of two monoclonal antibodies represent promising safe and efficacious biological for use in PEP as a replacement for F(ab)2 fragments or immune globulins.