ChemInform Abstract: Intimate Molecular Interactions of P. falciparum Merozoite Proteins Involved in Invasion of Red Blood Cells and Their Implications for Vaccine Design

Rodrı́guez, Luis E.; Curtidor, Hernando; Urquiza, Mauricio; Cifuentes, Gladys; Reyes, Claudia; Patarroyo, Manuel Elkín

doi:10.1002/chin.200850274

Cited by 31 publications

(121 citation statements)

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“…In both rabbits and humans, more anti-MSP1 42 antibodies were required to reach 50% inhibition than anti-AMA1 antibodies. Although we do not know the mechanism responsible for this difference, one hypothesis is that more anti-MSP1 42 antibodies are required to block the growth, as MSP1 42 protein is the most abundant protein on the surface of the merozoite while AMA1 protein is presented only in the merozoite's apical pole (4,25). This study also shows different Ab 50 s not only between antigens but also between species immunized.…”

Section: Discussionmentioning

confidence: 73%

“…Apical membrane antigen 1 (AMA1) and the 42-kDa merozoite surface protein 1 fragment (MSP1 42 ) are leading vaccine candidates, and various evidence from epidemiologic and animal studies supports these proteins as potential vaccine targets (8,33). Both proteins are expressed on the surface of merozoites (the invasive form of the blood-stage parasite) and are thought to have an important role in the invasion process; MSP1 is responsible for initial attachment and AMA1 for reorientation (9,18,25).…”

mentioning

confidence: 99%

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Anti-Apical-Membrane-Antigen-1 Antibody Is More Effective than Anti-42-Kilodalton-Merozoite-Surface-Protein-1 Antibody in Inhibiting Plasmodium falciparum Growth, as Determined by the In Vitro Growth Inhibition Assay

Miura

Zhou

Diouf

et al. 2009

Clin Vaccine Immunol

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Apical membrane antigen 1 (AMA1) and the 42-kDa merozoite surface protein 1 (MSP1 42 ) are leading malaria vaccine candidates. Several preclinical and clinical trials have been conducted, and an in vitro parasite growth inhibition assay has been used to evaluate the biological activities of the resulting antibodies. In a U.S. phase 1 trial with AMA1-C1/Alhydrogel plus CPG 7909, the vaccination elicited anti-AMA1 immunoglobulin G (IgG) which showed up to 96% inhibition. However, antibodies induced by MSP1 42 -C1/Alhydrogel plus CPG 7909 vaccine showed less than 32% inhibition in vitro. To determine whether anti-MSP1 42 IgG had less growth-inhibitory activity than anti-AMA1 IgG in vitro, the amounts of IgG that produced 50% inhibition of parasite growth (Ab 50 ) were compared for rabbit and human antibodies. The Ab 50 s of rabbit and human anti-MSP1 42 IgGs were significantly higher (0.21 and 0.62 mg/ml, respectively) than those of anti-AMA1 IgGs (0.07 and 0.10 mg/ml, respectively) against 3D7 parasites. Ab 50 data against FVO parasites also demonstrated significant differences. We further investigated the Ab 50 s of mouse and monkey anti-AMA1 IgGs and showed that there were significant differences between the species (mouse, 0.28 mg/ml, and monkey, 0.14 mg/ml, against 3D7 parasites). Although it is unknown whether growth-inhibitory activity in vitro reflects protective immunity in vivo, this study showed that the Ab 50 varies with both antigen and species. Our data provide a benchmark for antibody levels for future AMA1-or MSP1 42 -based vaccine development efforts in preclinical and clinical trials.

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Section: Discussionmentioning

confidence: 73%

mentioning

confidence: 99%

Anti-Apical-Membrane-Antigen-1 Antibody Is More Effective than Anti-42-Kilodalton-Merozoite-Surface-Protein-1 Antibody in Inhibiting Plasmodium falciparum Growth, as Determined by the In Vitro Growth Inhibition Assay

Miura

Zhou

Diouf

et al. 2009

Clin Vaccine Immunol

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“…Concurrently with Mrz binding to RBC membrane, a group of 11 merozoite surface proteins (MSP) is used in conjunction to bind to and invade erythrocytes; some of them are a n c h o r e d t o t h e m e m b r a n e v i a glicosylphosphatidylinositol (GPI) prosthetic group, others traverse the membrane and some others bind loosely to the membrane or to other MSP proteins (Rodriguez et al, 2008).…”

Section: Escape Mechanismmentioning

confidence: 99%

“…The top part of each box shows (in parenthesis) the total number of sequences taken from the redundant (NR) NCBI database; the amount of sequences used in multiple sequence alignment (selected or filtered by phylogenetic analysis) is shown to the left of the number in parenthesis. The numbers for the amino acids in the CSP-1 and TRAP TSR domain sequences are from the encoding system reported by Rodriguez et al, 2008. ! 69 cHABPs of Plasmodium falciparum mediated (after prodomain removal) by AMA-1 domains I and II where cHABPs 4313 ( 134 DAEVAGTQYRLPSGKCPVFG 153 ) (DI) and 4325 ( 374 MIKSAFLPTGAFKADRYKSH 393 ) (DII) form a trough or channel stabilised by H-bonds where an as-yet-unknown receptor binds ( Figure 2C, blue and dark yellow) (Bai et al, 2005).…”

Section: Escape Mechanismmentioning

confidence: 99%

“…The top part of each box shows (in parenthesis) the total number of sequences taken from the redundant (NR) NCBI database; the amount of sequences used in multiple sequence alignment (selected or filtered by phylogenetic analysis) is shown to the left of the number in parenthesis. The numbers for the amino acids in the EBA-175 and MSP-1 19 kDa sequences are from the encoding system reported by Rodriguez et al, 2008. 2005). These cHABPs could also be sequential, a s o c c u r s w i t h T R A P c H A B P s 3 2 8 7 ( 241 TA S C G V W D E W S P Y S V 255 ) a n d 3 2 8 9 ( 251 S P C S V T Y G K G T R S R K 265 ) f o r m i n g a positively-charged trough where negativelycharged receptors bind, like heparin and HSPG (Tossavainen et al, 2006).…”

Section: Escape Mechanismmentioning

confidence: 99%

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Far from the Madding Crowd: the Molecular Basis for Immunological Escape ofPlasmodium falciparum

Patarroyo¹,

Aza-Conde²,

Moreno-Vranich³

et al. 2017

Current Issues in Molecular Biology

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Like Thomas Hardy's famous novel Far from the Madding Crowd, Plasmodium falciparum parasites display their most relevant survival structures (proteins) involved in host cell invasion far away from the immune system's susceptible regions, displaying tremendous genetic variability, to attract the immune response and escape immune pressure. The 3D structure localisation of the conserved amino acid sequences of this deadly parasite's most relevant proteins involved in host cell invasion, as well as the location of the highly polymorphic, h i g h l y i m m u n o g e n i c r e g i o n s , c l e a r l y demonstrates that such structures are far apart, sometimes 90° to 180° opposite, thereby rendering the immune response useless. It is also shown here that these conserved, f u n c t i o n a l l y -r e l e v a n t s t r u c t u r e s a r e immunologically silent, since no immune response has been induced.

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Conserved regions from Plasmodium falciparum MSP11 specifically interact with host cells and have a potential role during merozoite invasion of red blood cells

Obando-Martinez

Curtidor

Vanegas

et al. 2010

J of Cellular Biochemistry

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Despite significant global efforts, a completely effective vaccine against Plasmodium falciparum, the species responsible for the most serious form of malaria, has not been yet obtained. One of the most promising approaches consists in combining chemically synthesized minimal subunits of parasite proteins involved in host cell invasion, which has led to the identification of peptides with high binding activity (named HABPs) to hepatocyte and red blood cell (RBC) surface receptors in a large number of sporozoite and merozoite proteins, respectively. Among these proteins is the merozoite surface protein 11 (MSP11), which shares important structural and immunological features with the antimalarial vaccine candidates MSP1, MSP3, and MSP6. In this study, 20-mer-long synthetic peptides spanning the complete sequence of MSP11 were assessed for their ability to bind specifically to RBCs. Two HABPs with high ability to inhibit invasion of RBCs in vitro were identified (namely HABPs 33595 and 33606). HABP-RBC bindings were characterized by means of saturation assays and Hill analysis, finding cooperative interactions of high affinity for both HABPs (n(H) of 1.5 and 1.2, K(d) of 800 and 600 nM for HABPs 33595 and 33606, respectively). The nature of the possible RBC receptors for MSP11 HABPs was studied in binding assays to enzyme-treated RBCs and cross-linking assays, finding that both HABPs use mainly a sialic acid-dependent receptor. An analysis of the immunological, structural and polymorphic characteristics of MSP11 HABPs supports including these peptides in further studies with the aim of designing a fully effective protection-inducing vaccine against malaria.

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ChemInform Abstract: Intimate Molecular Interactions of P. falciparum Merozoite Proteins Involved in Invasion of Red Blood Cells and Their Implications for Vaccine Design

Cited by 31 publications

References 1 publication

Anti-Apical-Membrane-Antigen-1 Antibody Is More Effective than Anti-42-Kilodalton-Merozoite-Surface-Protein-1 Antibody in Inhibiting Plasmodium falciparum Growth, as Determined by the In Vitro Growth Inhibition Assay

Anti-Apical-Membrane-Antigen-1 Antibody Is More Effective than Anti-42-Kilodalton-Merozoite-Surface-Protein-1 Antibody in Inhibiting Plasmodium falciparum Growth, as Determined by the In Vitro Growth Inhibition Assay

Far from the Madding Crowd: the Molecular Basis for Immunological Escape ofPlasmodium falciparum

Conserved regions from Plasmodium falciparum MSP11 specifically interact with host cells and have a potential role during merozoite invasion of red blood cells

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