Table 1 Summary of DNA vaccine optimization in parasites

Genetic Adjuvant

Co-immunization of merozoite surface protein-1 (MSP1) of P. yoelii with IL-12 in A/J mice elicited strong Th1 type responses characterized by high levels of IFN-γ. Parasite specific antibodies also protected against parasite infection.

Construction of DNA plasmid encoding C-terminal region of MSP1 (P. falciparum) was tested with plamids expressing GM-CSF or recombinant GM-CSF protein in monkeys. Co-immunization with GM-CSF protein lead to higher Ab titers and higher response to boosting with MSP1.

MuStDO5 is a multivalent vaccine composed of 5 plasmids encoding P. falciparum proteins and GM-CSF. When tested for safety in mice and rabbits via i.m/i.d. injections, the vaccine was determined safe and well tolerated without development of autoimmunity.

Vaccination with plasmids encoding L. amazonensis P4 nuclease, HSp70 or murine IL-12 was tested in the susceptible Balb/c mouse model. Co-immunization with P4 nuclease and IL-12 protected mice against parasite challenge as determined by 4 log reduction in parasite burden and increased levels of IFN-γ and TNF-α.

Following p36/LACK prime-boost immunization with a combination of DNA vectors expressing IL-12 and IL-18 in mice, highest protection was observed compared to controls.

Co-administration of DNA plasmids encoding IL-18 and S. mansoni glutathione S-transferase elicited 30 fold increase in antigen specific IFN-γ secreting cells, 28% reduction in egg laying and 23% reduction in worm burden in mice.

Multivalent vaccine

Prime boost regimen with vectors encoding functional domains of TRAP and CS antigens of P. cynomogli was more effective at reducing peak parasitemia in rhesus monkeys.

A multistage P. knowlesi vaccine with plasmids encoding 2 pre-erythrocytic, 2 blood stage antigens and GM-CSF was administered to rhesus monkeys followed by a boost with a pox virus encoding all 4 antigens. Monkeys developped Abs against sporozoites, infected erythrocytes and CPS protein.

Six pre-erythrocytic antigens linked together to produce a polyprotein in a DNA vaccine and either MVA or FP9 were tested in mice against P. falciparum. Greater responses were seen when a heterologous viral regimen was used, producing multispecific T cells.

L. major TSA and LmST11 antigens were expressed either as single genes or as digene construct and tested in the susceptible Balb/c model. Administration of the genes in either constructs lead to protection via polyspecific immune responses.

Three doses of 4 plasmids encoding S. japonicum antigens, Sj62, Sj28, Sj23 and Sj14 3-3-, induced high levels of IFN-γ and partial protection from challenge infection when administered in mice.

DNA plasmids encoding either Entamoeba histolytica cysteine protease 112 or adhesin 112 were co-administered to hamsters, leading to protection against liver abscess formation. No protection was observed with either plasmid alone.

Codon optimization

P. falciparum erythrocyte binding protein and MSP1 antigens were codon optimized for expression in mammals. 10 to 100 fold less optimized plasmid DNA was required to induce high Ab titers in mice.