Comparative Efficacy of Intramuscular and Scarification Routes of Administration of Live Smallpox Vaccine in a Murine Challenge Model

In recent years concern has mounted regarding the possibility of a re-emergence of smallpox through biowarfare or bioterrorism. There is also concern over the incidence of human monkeypox in endemic areas and the potential for monkeypox to be accidentally transported to non-endemic areas. In the event of re-emergence of smallpox or emergence of monkeypox, the accepted route of administration for live replicating smallpox vaccine is dermal scarification, which generates a virus-shedding lesion that persists for several days at the vaccination site. The lesion is a potential source of contact transmission of vaccine to individuals who may be contra-indicated for receipt of the live vaccine. In this study, we compare dermal scarification with intramuscular vaccination for replicating smallpox vaccine in a mouse lethal challenge model. Comparisons are made over multiple vaccine and challenge doses and data recorded for lethality, disease severity, and antibody responses. Qualitative and quantitative differences between the two routes are observed, and for the intramuscular route the febrile response is not suppressed after subsequent virulent vaccinia virus challenge. However both routes generate an immune response and protect from severe disease and death. Although dermal scarification is the preferred route of vaccination for the general population, intramuscular vaccination may be an option for people who are not contraindicated for the live vaccine, but who are close contacts of people who are contraindicated for the live vaccine, in an emergency situation.