Immunogenicity and protective efficacy of a Plasmodium yoelii Hsp60 DNA vaccine in BALB/c mice

The gene encoding the 60-kDa heat shock protein of Plasmodium yoelii (PyHsp 60) was cloned into the VR1012 and VR1020 mammalian expression vectors. Gro ups of 10 BALB/c mice were immunized intramuscularly at 0, 3, and 9 weeks w ith 100 mug of PyHsp60 DNA vaccine alone or in combination with 30 mug of p murGMCSF, Sera from immunized mice but not from vector control groups recog nized P. yoelii sporozoites, liver stages, and infected erythrocytes in an indirect fluorescent antibody test. Two weeks after the last immunization, mice were challenged with 50 P. yoelii sporozoites, In one experiment the v accine pPyHsp60-VR1012 used in combination with pmurGMCSF gave 40% protecti on (Fisher's exact test; P = 0.03, vaccinated versus control groups). In a second experiment this vaccine did not protect any of the immunized mice bu t induced a delay in the onset of parasitemia. In neither experiment was th ere any evidence of a protective effect against the asexual erythrocytic st age of the life cycle. In a third experiment mice were primed with PrHsp60 DNA, were boosted 2 weeks later with 2 x 10(3) irradiated P. yoelii sporozo ites, and were challenged several weeks later. The presence of PyHsp60 in t he immunization regimen did not lead to reduced blood-stage infection or de velopment of parasites in hepatocytes. PyHsp60 DNA vaccines were immunogeni c in BALB/c mice but did not consistently, completely protect against sporo zoite challenge. The observation that in some of the PyHsp60 DNA vaccine-im munized mice there was protection against infection or a delay in the onset of parasitemia after sporozoite challenge deserves further evaluation.