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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 lethal Plasmodium chabaudi chabaudi PC1 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 pPcMSP1(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.

SUBMITTER: Wunderlich G

PROVIDER: S-EPMC101545 | biostudies-literature | 2000 Oct

REPOSITORIES: biostudies-literature

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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 lethal Plasmodium chabaudi chabaudi PC1 infection.

Wunderlich G G Moura I C IC del Portillo H A HA

Infection and immunity 20001001 10

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. ...[more]

PMID: 10992493

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Project description:BACKGROUND:Plasmodium falciparum merozoite surface protein-1 (PfMSP-1) and -2 (PfMSP-2) are major blood-stage vaccine candidate antigens. Understanding the genetic diversity of the genes, pfmsp-1 and pfmsp-2, is important for recognizing the genetic structure of P. falciparum, and the development of an effective vaccine based on the antigens. In this study, the genetic diversities of pfmsp-1 and pfmsp-2 in the Myanmar P. falciparum were analysed. METHODS:The pfmsp-1 block 2 and pfmsp-2 block 3 regions were amplified by polymerase chain reaction from blood samples collected from Myanmar patients who were infected with P. falciparum in 2013-2015. The amplified gene fragments were cloned into a T&A vector, and sequenced. Sequence analysis of Myanmar pfmsp-1 block 2 and pfmsp-2 block 3 was performed to identify the genetic diversity of the regions. The temporal genetic changes of both pfmsp-1 and pfmsp-2 in the Myanmar P. falciparum population, as well as the polymorphic diversity in the publicly available global pfmsp-1 and pfmsp-2, were also comparatively analysed. RESULTS:High levels of genetic diversity of pfmsp-1 and pfmsp-2 were observed in the Myanmar P. falciparum isolates. Twenty-eight different alleles of pfmsp-1 (8 for K1 type, 14 for MAD20 type, and 6 for RO33 type) and 59 distinct alleles of pfmsp-2 (18 for FC27, and 41 for 3D7 type) were identified in the Myanmar P. falciparum population in amino acid level. Comparative analyses of the genetic diversity of the Myanmar pfmsp-1 and pfmsp-2 alleles in the recent (2013-2015) and past (2004-2006) Myanmar P. falciparum populations indicated the dynamic genetic expansion of the pfmsp-1 and pfmsp-2 in recent years, suggesting that a high level of genetic differentiation and recombination of the two genes may be maintained. Population genetic structure analysis of the global pfmsp-1 and pfmsp-2 also suggested that a high level of genetic diversity of the two genes was found in the global P. falciparum population. CONCLUSION:Despite the recent remarkable decline of malaria cases, the Myanmar P. falciparum population still remains of sufficient size to allow the generation and maintenance of genetic diversity. The high level of genetic diversity of pfmsp-1 and pfmsp-2 in the global P. falciparum population emphasizes the necessity for continuous monitoring of the genetic diversity of the genes for better understanding of the genetic make-up and evolutionary aspect of the genes in the global P. falciparum population.

Dataset Information

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 lethal Plasmodium chabaudi chabaudi PC1 infection.

Publications

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 lethal Plasmodium chabaudi chabaudi PC1 infection.

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