Direct immunization of malaria DNA vaccine into the liver by gene gun protects against lethal challenge of Plasmodium berghei sporozoite

The liver is the first target organ for malaria parasites immediately after the bite of an infected mosquito. We studied local immunization of malaria DNA vaccines at the site of the liver using a gene gun as a useful tool fo r in vivo transfection of foreign genes. A malaria DNA vaccine consisting o f the Plasmodium berghei circumsporozoite protein (PbCSP) gene plus the mou se IL-12 gene was bombarded directly by a gene gun into mouse liver once or into the skin twice. A marked protective effect was induced by gene bombar dment into the liver (more than 71%) compared with that into the skin (less than 33%). A Th1-type immune response and high production of iNOS were obs erved in the hepatic lymphocytes from mice bombarded into the liver, result ing in more effective protection compared with those bombarded into the ski n. These results provide an important implication on the development of eff icient malaria vaccine strategies. (C) 2000 Academic Press.