Delayed-type hypersensitivity and protection in mice following immunization with Plasmodium berghei sporozoites

The measurement of footpad swelling (FPS) following the inoculation of sporozoite antigen (Ag) into the hind footpad (HFP) of outbred mice was used as an in vivo test of delayed-type hypersensitivity (DTH) to attenuated sporozoite immunization. An attempt was made to correlate DTH with protective antisporozoite immunity. The optimum time for testing DTH following a single intravenous immunization was four days. The optimum sensitizing dose was 1 x 10(5) attenuated sporozoites. A single immunization gave a greater FPS than multiple immunizations. Mice immunized with irradiation-attenuated sporozoites could be protected from a lethal challenge with nonattenuated sporozoites. The FPS response to mosquito debris Ag was minimal in mice sensitized by bites from infected mosquitos. Nude mice failed to develop an FPS response and could not mount a protective immunity with attenuated sporozoites. However, splenectomized mice did have an FPS response following sensitization. Mice infected with blood-stage parasites had negligible FPS response to sporozoite Ag. The FPS response to sporozoite Ag proved to be a correlate of DTH in mice sensitized with sporozoites.