Genetic Vaccination against Malaria Infection by Intradermal and Epidermal Injections of a Plasmid Containing the Gene Encoding thePlasmodium bergheiCircumsporozoite Protein

• DOI: 10.1128/iai.68.10.5914-5919.2000
• Publication Date: 2002-07-27T06:01:09Z
• Authors: Richard Weiss; Wolfgang W. Leitner; Sandra Scheiblhofer; Defeng Chen; Andrea Bernhaupt; Sven Mostböck; Josef Thalhamer; Jeffrey A. Lyon
• Keywords: 0301 basic medicine; Mice, Inbred BALB C; Injections, Intradermal; Plasmodium berghei; Vaccination; Protozoan Proteins; Antibodies, Protozoan; Biolistics; Lymphocyte Activation; 3. Good health; Malaria; Mice; 03 medical and health sciences; Malaria Vaccines; Vaccines, DNA; Animals; Cytokines; Spleen; Plasmids; T-Lymphocytes, Cytotoxic

ABSTRACTThe circumsporozoite protein (CSP) from the surface of sporozoite stagePlasmodiumsp. malaria parasites is among the most important of the malaria vaccine candidates. Gene gun injection of genetic vaccines encodingPlasmodium bergheiCSP induces a significant protective effect against sporozoite challenge; however, intramuscular injection does not. In the present study we compared the immune responses and protective effects induced byP. bergheiCSP genetic vaccines delivered intradermally with a needle or epidermally with a gene gun. Mice were immunized three times at 4-week intervals and challenged by a single infectious mosquito bite. Although 50 times more DNA was administered by needle than by gene gun, the latter method induced significantly greater protection against infection. Intradermal injection of the CSP genetic vaccine induced a strong Th1-type immune response characterized by a dominant CSP-specific immunoglobulin G2a (IgG2a) humoral response and high levels of gamma interferon produced by splenic T cells. Gene gun injection induced a predominantly Th2-type immune response characterized by a high IgG1/IgG2a ratio and significant IgE production. Neither method generated 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.