Protection against Plasmodium falciparum malaria in chimpanzees by immunization with the conserved pre-erythrocytic liver-stage antigen 3

Daubersies, Pierre; Thomas, Alan W.; Millet, Pascal; Brahimi, Karima; Langermans, Jan A. M.; Ollomo, Benjamin; Moham, L.B.; Slierendrecht, B.; Eling, W.M.C.; Belkum, Alex van; Dubreuil, G; Meis, Jacques F.; Guérin-Marchand, Claudine; Cayphas, Sylvie; Cohen, Joe; Grasse-Mas, H.; Druihle, Pierre

doi:10.1038/81366

Cited by 154 publications

(188 citation statements)

References 30 publications

Supporting

Mentioning

170

Contrasting

Order By: Relevance

“…Finally, it is noteworthy that none of our ESTs resulted in significant matches with sporozoite-threonine asparagine-rich protein and liver stage antigen-3, proteins that have been described in P. falciparum sporozoites (12,13).…”

Section: Resultsmentioning

confidence: 99%

“…Both proteins are found in all Plasmodium species examined. A few other sporozoite antigens have been identified in P. falciparum (12,13), but their function is unknown.To facilitate the identification of genes that are expressed in the sporozoite stage, we have constructed a cDNA library from salivary gland sporozoites of the rodent malaria parasite Plasmodium yoelii and generated 1,972 expressed sequence tags (ESTs). We document the quality of the library by the presence of CS and SSP2͞TRAP transcripts and the absence of erythrocytic stage-specific transcripts.…”

mentioning

confidence: 99%

“…Both proteins are found in all Plasmodium species examined. A few other sporozoite antigens have been identified in P. falciparum (12,13), but their function is unknown.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Exploring the transcriptome of the malaria sporozoite stage

Kappe

Gardner

Brown

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

125

View full text Add to dashboard Cite

Most studies of gene expression in Plasmodium have been concerned with asexual and͞or sexual erythrocytic stages. Identification and cloning of genes expressed in the preerythrocytic stages lag far behind. We have constructed a high quality cDNA library of the Plasmodium sporozoite stage by using the rodent malaria parasite P. yoelii, an important model for malaria vaccine development. The technical obstacles associated with limited amounts of RNA material were overcome by PCR-amplifying the transcriptome before cloning. Contamination with mosquito RNA was negligible. Generation of 1,972 expressed sequence tags (EST) resulted in a total of 1,547 unique sequences, allowing insight into sporozoite gene expression. The circumsporozoite protein (CS) and the sporozoite surface protein 2 (SSP2) are well represented in the data set. A BLASTX search with all tags of the nonredundant protein database gave only 161 unique significant matches (P(N) < 10 ؊4 ), whereas 1,386 of the unique sequences represented novel sporozoite-expressed genes. We identified ESTs for three proteins that may be involved in host cell invasion and documented their expression in sporozoites. These data should facilitate our understanding of the preerythrocytic Plasmodium life cycle stages and the development of preerythrocytic vaccines.Plasmodium yoelii yoelii ͉ expressed sequence tag P rotozoan parasites of the genus Plasmodium are the causative agents of malaria, the most devastating parasitic disease in humans. The parasites occur in distinct morphological and antigenic stages as they progress through a complex life cycle, thwarting decades of efforts to develop an effective malaria vaccine. Plasmodium is transmitted via the bite of an infected Anopheles mosquito, which releases the sporozoite stage into the skin. Sporozoites enter the bloodstream and, on reaching the liver, invade hepatocytes and develop into exo-erythrocytic forms (EEF). After multiple cycles of DNA replication, the EEF contains thousands of merozoites (liver schizont) that are released into the blood stream and initiate the erythrocytic cycle (asexual blood stage) that causes the disease malaria. Changes in life cycle stages are accompanied by major changes in gene expression and therefore by major changes in antigenic composition. The form of the parasite best studied is the asexual blood stage, mainly because of its comparatively easy experimental accessibility. Therefore, most Plasmodium proteins that have been well characterized are expressed during the erythrocytic cycle, among them some major erythrocytic-stage vaccine candidates such as merozoite surface protein-1 (MSP-1) and apical membrane antigen-1 (AMA-1; ref. 1). Erythrocytic-stage vaccines are aimed at inducing an immune response that suppresses or eradicates parasite load in the blood. In contrast, preerythrocytic vaccines are aimed at eliciting an immune response that destroys the sporozoites and the EEF, thereby preventing progression of the parasite to the blood stage. The feasibility of a preerythrocytic v...

show abstract

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Exploring the transcriptome of the malaria sporozoite stage

Kappe

Gardner

Brown

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

125

View full text Add to dashboard Cite

show abstract

“…26 PfEXP1: PfEXP1 recombinant protein used in the ELISA was a gift from Hoffmann-La Roche, Basel, Switzerland. The full-length Exp-1 gene, also known as 5.1 antigen, was cloned from the K1 strain of P. falciparum and was produced in vitro from recombinant plasmid pUC8-5.1 and purified as previously described.…”

Section: Immunization Groupsmentioning

confidence: 99%

Effect on antibody and T-cell responses of mixing five GMP-produced DNA plasmids and administration with plasmid expressing GM-CSF

et al. 2004

View full text Add to dashboard Cite

One potential benefit of DNA vaccines is the capacity to elicit antibody and T-cell responses against multiple antigens at the same time by mixing plasmids expressing different proteins. A possible negative effect of such mixing is interference among plasmids regarding immunogenicity. In preparation for a clinical trial, we assessed the immunogenicity of GMP-produced plasmids encoding five Plasmodium falciparum proteins, PfCSP, PfSSP2, PfEXP1, PfLSA1, and PfLSA3, given as a mixture, or alone. The mixture induced higher levels of antibodies against whole parasites than did the individual plasmids, but was associated with a decrease in antibodies to individual P. falciparum proteins. T-cell responses were in general decreased by administration of the mixture. Immune responses to individual plasmids and mixtures were generally higher in inbred mice than in outbreds. In inbred BALB/c and C57BL/6 mice, coadministration of a plasmid expressing murine granulocyte-macrophage colony-stimulating factor (mGM-CSF), increased antibody and T-cell responses, but in outbred CD-1 mice, coadministration of mGM-CSF was associated with a decrease in antibody responses. Such variability in data from studies in different strains of mice underscores the importance of genetic background on immune response and carefully considering the goals of any preclinical studies of vaccine mixtures planned for human trials.

show abstract

“…[36][37][38] Several other molecules are being channelled into human trials on the basis of results considered promising and obtained in one of the primate, mouse, or in-vitro models (figure 1). [39][40][41][42][43] Clinical trials will be essential to show whether these results can be extended to human beings.…”

Section: Personal Viewmentioning

confidence: 99%