Genetic Immunization of BALB/c mice with a Plasmid Bearing the Gene Coding for a Hybrid Merozoite Surface Protein 1-Hepatitis B Virus Surface Protein Fusion Protects Mice against LethalPlasmodium chabaudi chabaudiPC1 Infection

Abstract

The genetic immunization of rodents with a plasmid coding for a Plasmodium chabaudi merozoite surface protein 1 (C terminus)-hepatitis B virus surface fusion protein (pPcMSP1 19 -HBs) provided protection of mice against subsequent lethal challenge with P. chabaudi chabaudi PC1-infected red blood cells. The percentage of survivor mice was higher in DNA-immunized mice than in animals immunized with a recombinant rPcMSP1 19 -glutathione S-transferase fusion protein administered in Freund adjuvant. In all mice immunized with the pPc-MSP1 19 -HBs, a Th1-specific response, including the production of anti-MSP1 19 -specific immunoglobulins predominantly of the immunoglobulin G2a subtype and reacting almost exclusively against discontinuous epitopes, was elicited. The coinjection of Th1-type cytokine-expressing plasmids (gamma interferon, interleukin-2, and granulocyte-macrophage colony-stimulating factor) mostly abolished protection and boosting of MSP1 19 -specific antibodies. The inclusion of a lymph node-targeting signal did not significantly increase protection. These data provide further evidence that MSP1 19 -HBs DNA constructs might be useful as components of a genetic vaccine against the asexual blood stages of Plasmodium.

DNA Vaccine Against Malaria: A Long Way To Go

“…The inclusion of a lymph node-targeting signal did not significantly increase protection. Further, these results support that MSP1(19)-HBs DNA constructs might be useful as components of a genetic vaccine against the asexual blood stages of Plasmodium (Wunderlich et al, 2000).…”

“…It has been shown that the genetic immunization of rodents with a plasmid coding for a P. chabaudi MSP1 (C terminus)-hepatitis B virus surface fusion protein (pPcMSP1(19)-HBs) provided protection of mice against subsequent lethal challenge with P. chabaudi chabaudi PC1-infected red blood cells (Table 1) (Wunderlich et al, 2000). The percentage of survivor mice was higher in DNA-immunized mice than in animals immunized with a recombinant rPcMSP1(19)-glutathione-S-transferase fusion protein administered in freund adjuvant.…”

Genetic linkage of autologous T cell epitopes in a chimeric recombinant construct improves anti-parasite and anti-disease protective effect of a malaria vaccine candidate

“…The cellular response to MSP1 19 seems to improve when a denatured recombinant protein is used as immunogen [35]. Several approaches have been used to enhance the immunogenicity of the MSP1 19 fragment that include the conjugation of exogenous T cell epitopes to a MSP1 19 fusion protein [60], the fusion of MSP1 19 to novel protein adjuvants [61], the genetic linkage to hepatitis B virus surface protein [62, 63] or the genetic linkage to promiscuous T cell epitopes [40, 42, 64]. The PyRMC-MSP1 19 described here includes two endogenous putative promiscuous T cell epitopes genetically linked to an extended PyMSP1 19 protein fragment, which includes a region predicted to contain additional putative promiscuous T cell epitopes.…”

Viral vectored granulocyte-macrophage colony stimulating factor inhibits vaccine protection in an SIV challenge model: Protection correlates with neutralizing antibody

“…GM-CSF has been used extensively as an adjuvant in plasmid DNA immunizations where it has generally been shown to enhance humoral and cellular immune responses (1, 2, 15, 16). However, some studies have indicated that GM-CSF can reduce immune responses (17, 33, 34). Because non-human primate studies are often better than mouse studies at predicting vaccine efficacy in humans, we tested the effects of GM-CSF expressed from a VSV vector in an SIV vaccine study done in parallel with our previous published study (27).…”