Genetic vaccination against malaria infection by intradermal and epidermalinjections of a plasmid containing the gene encoding the Plasmodium berghei circumsporozoite protein

The circumsporozoite protein (CSP) from the surface of sporozoite stage Pla smodium sp. malaria parasites is among the most important of the malaria va ccine candidates. Gene gun injection of genetic vaccines encoding Plasmodiu m berghei CSP induces a significant protective effect against sporozoite ch allenge; however, intramuscular injection does not. In the present study we compared the immune responses and protective effects induced by P. berghei CSP genetic vaccines delivered intradermally with a needle or epidermally with a gene gun. Mice were immunized three times at 4-week intervals and ch allenged by a single infectious mosquito bite. Although 50 times more DNA w as administered by needle than by gene gun, the latter method induced signi ficantly greater protection against infection. Intradermal injection of the CSP genetic vaccine induced a strong Th1-type immune response characterize d by a dominant CSP-specific immunoglobulin G2a (IgG2a) humoral response an d high levels of gamma interferon produced by splenic T cells. Gene gun inj ection induced a predominantly Th2-type immune response characterized by a high IgG1/IgG2a ratio and significant IgE production. Neither method genera ted measurable cytotoxic T lymphocyte activity. The results indicate that a gene gun-mediated CS-specific Th2-type response may be best for protecting against malarial sporozoite infection when the route of parasite entry is via mosquito bite.