Cloning and characterization of a novel Plasmodium falciparum sporozoite surface antigen, STARP

Fidock, David A.; Bottius, Emmanuel; Brahimi, Karima; Inge, I.M.D.; Moelans,; Aikawa, Masamichi; Konings, Ruud N. H.; Certa, Ulrich; Olafsson, Pétur; Kaidoh, Toshiyuki; Asavanich, Achara; Guérin-Marchand, Claudine; Druilhe, Pierre

doi:10.1016/0166-6851(94)00012-3

Cited by 72 publications

(57 citation statements)

References 36 publications

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“…Asparagine is the most commonly used (ϳ12%) amino acid in P. falciparum, followed by lysine and glutamic acid (ϳ10%) (33,34). Two other sporozoite surface proteins, CS and the sporozoite-threonine-and-asparagine-rich protein (STARP) (35), contain 29% and 25% asparagine, respectively. It has been speculated that asparagine-rich motifs in the amino acid sequence might be targets of opsonizing antibodies, promoting parasite phagocytosis by immune cells (36 -38).…”

Section: Resultsmentioning

confidence: 99%

Stage-dependent Localization of a Novel Gene Product of the Malaria Parasite, Plasmodium falciparum

Nguyên¹,

Fujioka²,

Kang³

et al. 2001

Journal of Biological Chemistry

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A novel Plasmodium falciparum gene, MB2, was identified by screening a sporozoite cDNA library with the serum of a human volunteer protected experimentally by the bites of P. falciparum-infected and irradiated mosquitoes. The single-exon, single-copy MB2 gene is predicted to encode a protein with an M r of 187,000. The MB2 protein has an amino-terminal basic domain, a central acidic domain, and a carboxyl-terminal domain with similarity to the GTP-binding domain of the prokaryotic translation initiation factor 2. MB2 is expressed in sporozoites, the liver, and blood-stage parasites and gametocytes. The MB2 protein is distributed as a ϳ120-kDa moiety on the surface of sporozoites and is imported into the nucleus of blood-stage parasites as a ϳ66-kDa species. Proteolytic processing is favored as the mechanism regulating the distinct subcellular localization of the MB2 protein. This differential localization provides multiple opportunities to exploit the MB2 gene product as a vaccine or therapeutic target.

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Section: Resultsmentioning

confidence: 99%

Stage-dependent Localization of a Novel Gene Product of the Malaria Parasite, Plasmodium falciparum

Nguyên¹,

Fujioka²,

Kang³

et al. 2001

Journal of Biological Chemistry

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“…Therefore, discovery of liver-stages antigens has required methodologies that exploit recent discoveries of immunity targeting the liver-phase of infection. For example, immunological approaches using sera from individuals on antimalarial therapy (CPS-CQ or CPS-MQ) while in malaria-endemic regions were applied to screen libraries expressing Plasmodium peptides [51,52]. Later, similar approaches were applied using blood from individuals immunized with irradiated sporozoites to evaluate expression libraries for reactivity with antibodies [53,5 ], or T cell responses with peripheral blood mononuclear cells (P"MCs) [55].…”

Section: Antigen Discovery Efortsmentioning

confidence: 99%

“…ST"RP (Gen"ank: C""8122 .1) was identiied by screening a lambda library with antibodies developed in malaria exposed missionaries under chloroquine treatment [51]. It is a 60 -amino acid protein with a central hydrophilic region (amino acids 85 89) that contains a complex repetitive structure that can vary in size between diferent strains of P. falciparum.…”

Section: Structure and Antigenicitymentioning

confidence: 99%

“…It is a 60 -amino acid protein with a central hydrophilic region (amino acids 85 89) that contains a complex repetitive structure that can vary in size between diferent strains of P. falciparum. Two peptides from this repetitive region (Rp10 and Rp 5) have been evaluated in vaccines [51]. Even with variation in the repetitive structure, the protein is highly conserved across a variety of geographically separated strains [51,189].…”

Section: Structure and Antigenicitymentioning

confidence: 99%

“…Two peptides from this repetitive region (Rp10 and Rp 5) have been evaluated in vaccines [51]. Even with variation in the repetitive structure, the protein is highly conserved across a variety of geographically separated strains [51,189].…”

Section: Structure and Antigenicitymentioning

confidence: 99%

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Pre-Erythrocytic Vaccine Candidates in Malaria

Tucker¹,

Noe²,

Kotraiah³

et al. 2016

Current Topics in Malaria

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Abstract" vaccine providing sterile immunity against malaria has been shown to be possible with antigens from the pre-erythrocytic stages of malaria. Therefore, it is reasonable to focus vaccine development eforts on the pre-erythrocytic stages, consisting of both sporozoites and liver stage parasites, where it is expected that sterile immunity against the parasite can be elicited to block the development of blood stage infection, clinical disease, and resulting parasite transmission. "ccordingly, we will review the preclinical and clinical studies of malaria pre-erythrocytic eforts as well as highlight the advances, trends, and roadblocks encountered in these eforts.

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Lipopeptide immunization without adjuvant induces potent and long‐lasting B, T helper, and cytotoxic T lymphocyte responses against a malaria liver stage antigen in mice and chimpanzees

et al. 1997

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We have employed a 26-amino-acid synthetic peptide based on Plasmodium falciparum liver stage antigen-3 to evaluate improvements in immunogenicity mediated by the inclusion of a simple lipid-conjugated amino acid during peptide synthesis. Comparative immunization by the peptide in Freund's adjuvant or by the lipopeptide in saline shows that the addition of a palmitoyl chain can dramatically increase T helper (Th) cell responses in a wide range of major histocompatibility complex (MHC) class II haplotypes, to the extent that responses were induced in mice otherwise unable to respond to the non-modified peptide injected with Freund's adjuvant, and that the increased immunogenicity of the lipopeptide led to high and longer lasting antibody production (studied up to 8 months). B and T cell responses induced by the lipopeptide were reactive with native parasite protein epitopes, and a lipopeptide longer than ten amino acids was endogenously processed to associate with MHC class I and elicit cytotoxic T lymphocyte (CTL) responses. Finally, the lipopeptide was safe and highly immunogenic in chimpanzees, whose immune system is very similar to that of humans. Our results suggest that relatively large synthetic peptides, carefully chosen from pertinent areas of proteins and incorporating a simple palmitoyl-lysine, can induce not only CTL, but also strong Th and antibody responses in genetically diverse populations. Lipopeptides engineered in this way are simple to produce and purify under GMP conditions, they are well tolerated by apes, and with the enhanced immunogenicity without the need for adjuvant that we report here, they offer a quick and relatively low-cost route to provide material for human malaria vaccination trials.

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Cloning and characterization of a novel Plasmodium falciparum sporozoite surface antigen, STARP

Cited by 72 publications

References 36 publications

Stage-dependent Localization of a Novel Gene Product of the Malaria Parasite, Plasmodium falciparum

Stage-dependent Localization of a Novel Gene Product of the Malaria Parasite, Plasmodium falciparum

Pre-Erythrocytic Vaccine Candidates in Malaria

Lipopeptide immunization without adjuvant induces potent and long‐lasting B, T helper, and cytotoxic T lymphocyte responses against a malaria liver stage antigen in mice and chimpanzees

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