Protection against malaria by immunization with plasmid DNA encoding circumsporozoite protein.

Abstract

Immunization with irradiated sporozoites protects animals and h against malaria, and the circumsporozoite protein is a target of this protective immunity. We now report that adjuvant-free intramuscular injection of mice with plasmid DNA encding the Plasmodium yoeli circumsporozoite protein induced higher levels of antibodies and cytotoxic T lymphocytes against the P. yoel& circumsporozoite protein than did immunization with irradiated sporozoites. Mice immunized with this vaccine had an 86% reduction in liver-stage parasite burden after challenge with 5 x 10W sporozoites (>10 median infectious doses). Eiteen (68%) of 28 mice that received two or three doses of vaccine were protected against challenge with 102 sporozoites, and the protection was dependent on CD8+ T cells. These studies demonstrate the utility of plasmid DNA immunization against a nonviral infection. By obviating the requirement for peptide synthesis, expression and purification of recombinant proteins, and ad-

Impact of Recombinant Adenovirus Serotype 35 Priming versus Boosting of aPlasmodium falciparumProtein: Characterization of T- and B-Cell Responses to Liver-Stage Antigen 1

“…While antibodies have been correlated with protection from infection with the malaria parasite (25,27), T cells are believed to play a critical role in the elimination of liver-stage parasites and protection against the disease (29,36). Studies with mice indicate that a major mechanism of protection against liver-stage malaria is the production of IFN-␥ by activated CD8 ϩ T cells, which induces infected hepatocytes to synthesize nitric oxide, a molecule with a potent antiparasitic activity (8,13,50,51).…”

Superiority of the ear pinna over muscle tissue as site for DNA vaccination

“…After washing in PBS, organs were incubated in X-gal solution (5 mm K 3 Fe(CN) 6 , 5 mm K 4 Fe(CN) 6 , X 3 H 2 O), 2 mm MgCl 2 , 0.01% sodiumdesoxycholate, 0.02% NP40, 1 mg/ ml X-gal (Boehringer Mannheim) at 37°C for 3-16 h.…”

“…2 Direct DNA transfer has been successfully used for in vitro induction of both humoral and cellular immune responses to several antigens, including viruses such as influenza, hepatitis B, or HIV (human immunodeficiency virus), parasites, or tumor antigens. [3][4][5][6][7][8] Additionally, systemic effects were observed after transfer of cytokine genes. 9 It was assumed at the beginning that striated muscle is the only tissue in vitro suitable to take up and express naked DNA.…”

Safety of a GM-CSF adjuvant-plasmid DNA malaria vaccine

“…16 Toward the goal of developing an effective genetic malaria vaccine, a phase I trial was recently completed in healthy volunteers using a pDNA vaccine encoding the malaria circumsporozoite protein from Plasmodium falciparum (PfCSP), the causative agent of malaria. Although the final goal is to develop a multi-component, protective, pDNA-based vaccine, this single antigen, monovalent vaccine, was first tested alone in a phase I clinical trial to demonstrate its safety and immunogenicity.…”