Disruption of Plasmodium berghei merozoite surface protein 7 gene modulates parasite growth in vivo

Blood ◽  
2005 ◽  
Vol 105 (1) ◽  
pp. 394-396 ◽  
Author(s):  
Rita Tewari ◽  
Solabomi A. Ogun ◽  
Ruwani S. Gunaratne ◽  
Andrea Crisanti ◽  
Anthony A. Holder
Keyword(s):  
Plasmodium Falciparum ◽  
Gene Family ◽  
Plasmodium Berghei ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Plasmodium Yoelii ◽  
Parasite Growth ◽  
Surface Proteins ◽  
Rate Of Increase

Abstract Merozoite invasion of red blood cells is crucial to the development of the parasite that causes malaria. Merozoite surface proteins (MSPs) mediate the first interaction between parasite and erythrocyte. In Plasmodium falciparum, they include a complex of products from at least 3 genes (msp1, msp6, and msp7), one of which, msp7, is part of a gene family containing 3 and 6 adjacent members in Plasmodium yoelii and Plasmodium falciparum, respectively. We have identified and disrupted msp7 in the Plasmodium berghei gene family. The protein is expressed in schizonts and colocalizes with MSP1. The synthesis and processing of MSP1 was unaffected in the parasite with the disrupted gene (MSP7ko). Disruption of msp7 was not lethal but affected blood-stage parasite growth. MSP7ko parasites initially grew more slowly than wild-type parasites. However, when reticulocytes were prevalent, the rate of increase in parasitemia was similar, suggesting that MSP7ko parasites prefer to invade and grow within reticulocytes. (Blood. 2005;105:394-396)

scholarly journals Oral Immunization with a Combination of Plasmodium yoelii Merozoite Surface Proteins 1 and 4/5 Enhances Protection against Lethal Malaria Challenge

2004 ◽  
Vol 72 (10) ◽  
pp. 6172-6175 ◽  
Author(s):  
Lina Wang ◽  
Matthew W. Goschnick ◽  
Ross L. Coppel
Keyword(s):  
Escherichia Coli ◽  
Malaria Infection ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Oral Immunization ◽  
Plasmodium Yoelii ◽  
Antibody Responses ◽  
Surface Proteins ◽  
Merozoite Surface Protein 1

ABSTRACT Oral immunization of mice with Escherichia coli-expressed Plasmodium yoelii merozoite surface protein 4/5 or the C-terminal 19-kDa fragment of merozoite surface protein 1 induced systemic antibody responses and protected mice against lethal malaria infection. A combination of these two proteins administered orally conferred improved protection compared to that conferred by either protein administered alone.

scholarly journals Immunoglobulin G Subclass-Specific Responses against Plasmodium falciparum Merozoite Antigens Are Associated with Control of Parasitemia and Protection from Symptomatic Illness

2009 ◽  
Vol 77 (3) ◽  
pp. 1165-1174 ◽  
Author(s):  
Danielle I. Stanisic ◽  
Jack S. Richards ◽  
Fiona J. McCallum ◽  
Pascal Michon ◽  
Christopher L. King ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Immunoglobulin G ◽  
Vaccine Development ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Igg Subclass ◽  
Apical Membrane Antigen 1 ◽  
Falciparum Merozoite ◽  
Merozoite Antigens

ABSTRACT Substantial evidence indicates that antibodies to Plasmodium falciparum merozoite antigens play a role in protection from malaria, although the precise targets and mechanisms mediating immunity remain unclear. Different malaria antigens induce distinct immunoglobulin G (IgG) subclass responses, but the importance of different responses in protective immunity from malaria is not known and the factors determining subclass responses in vivo are poorly understood. We examined IgG and IgG subclass responses to the merozoite antigens MSP1-19 (the 19-kDa C-terminal region of merozoite surface protein 1), MSP2 (merozoite surface protein 2), and AMA-1 (apical membrane antigen 1), including different polymorphic variants of these antigens, in a longitudinal cohort of children in Papua New Guinea. IgG1 and IgG3 were the predominant subclasses of antibodies to each antigen, and all antibody responses increased in association with age and exposure without evidence of increasing polarization toward one subclass. The profiles of IgG subclasses differed somewhat for different alleles of MSP2 but not for different variants of AMA-1. Individuals did not appear to have a propensity to make a specific subclass response irrespective of the antigen. Instead, data suggest that subclass responses to each antigen are generated independently among individuals and that antigen properties, rather than host factors, are the major determinants of IgG subclass responses. High levels of AMA-1-specific IgG3 and MSP1-19-specific IgG1 were strongly predictive of a reduced risk of symptomatic malaria and high-density P. falciparum infections. However, no antibody response was significantly associated with protection from parasitization per se. Our findings have major implications for understanding human immunity and for malaria vaccine development and evaluation.

scholarly journals Truncation of Plasmodium berghei merozoite surface protein 8 does not affect in vivo blood-stage development

2008 ◽  
Vol 159 (1) ◽  
pp. 69-72 ◽  
Author(s):  
Tania F. de Koning-Ward ◽  
Damien R. Drew ◽  
Joanne M. Chesson ◽  
James G. Beeson ◽  
Brendan S. Crabb
Keyword(s):  
Plasmodium Berghei ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Blood Stage ◽  
Stage Development

Novel antimalarial antibodies highlight the importance of the antibody Fc region in mediating protection

Blood ◽  
2003 ◽  
Vol 102 (13) ◽  
pp. 4424-4430 ◽  
Author(s):  
Richard J. Pleass ◽  
Solabomi A. Ogun ◽  
David H. McGuinness ◽  
Jan G. J. van de Winkel ◽  
Anthony A. Holder ◽  
...  
Keyword(s):  
Passive Immunization ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Plasmodium Yoelii ◽  
Single Chain ◽  
Parasite Drug Resistance ◽  
Parasite Challenge ◽  
Major Target

Abstract Parasite drug resistance and difficulties in developing effective vaccines have precipitated the search for alternative therapies for malaria. The success of passive immunization suggests that immunoglobulin (Ig)-based therapies are effective. To further explore the mechanism(s) by which antibody mediates its protective effect, we generated human chimeric IgG1 and IgA1 and a single-chain diabody specific for the C-terminal 19-kDa region of Plasmodium yoelii merozoite surface protein 1 (MSP119), a major target of protective immune responses. These novel human reagents triggered in vitro phagocytosis of merozoites but, unlike their parental mouse IgG2b, failed to protect against parasite challenge in vivo. Therefore, the Fc region appears critical for mediating protection in vivo, at least for this MSP119 epitope. Such antibodies may serve as prototype therapeutic agents, and as useful tools in the development of in vitro neutralization assays with Plasmodium parasites. (Blood. 2003;102:4424-4430)

scholarly journals Immunogenicity and In Vivo Efficacy of Recombinant Plasmodium falciparum Merozoite Surface Protein-1 in Aotus Monkeys

1995 ◽  
Vol 1 (3) ◽  
pp. 325-332 ◽  
Author(s):  
Sanjai Kumar ◽  
Anjali Yadava ◽  
David B. Keister ◽  
Jing Hui Tian ◽  
Michael Ohl ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
In Vivo Efficacy ◽  
Merozoite Surface Protein 1 ◽  
Falciparum Merozoite

scholarly journals Factors Associated with Immunoglobulin G Subclass Polarization in Naturally Acquired Antibodies to Plasmodium falciparum Merozoite Surface Proteins: a Cross-Sectional Survey in Brazilian Amazonia

2006 ◽  
Vol 13 (7) ◽  
pp. 810-813 ◽  
Author(s):  
Kézia K. G. Scopel ◽  
Cor J. F. Fontes ◽  
Marcelo U. Ferreira ◽  
Érika M. Braga
Keyword(s):  
Plasmodium Falciparum ◽  
Immunoglobulin G ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Surface Proteins ◽  
Cross Sectional Survey ◽  
Cross Sectional ◽  
Falciparum Merozoite ◽  
Immunoglobulin G Subclass ◽  
Current Exposure

ABSTRACT We investigated immunoglobulin G (IgG) subclass antibody responses to Plasmodium falciparum merozoite surface protein 1 (MSP-1) and MSP-2 in 112 malaria-exposed subjects in Brazil. IgG3 polarization was primarily epitope driven, being little affected by cumulative or current exposure to malaria and not affected by a subject's age and Fcγ receptor IIA genotype.

scholarly journals Antigenic Characterization of an Intrinsically Unstructured Protein, Plasmodium falciparum Merozoite Surface Protein 2

2012 ◽  
Vol 80 (12) ◽  
pp. 4177-4185 ◽  
Author(s):  
Christopher G. Adda ◽  
Christopher A. MacRaild ◽  
Linda Reiling ◽  
Kaye Wycherley ◽  
Michelle J. Boyle ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Surface Protein ◽  
Variable Region ◽  
Intrinsic Property ◽  
Merozoite Surface Protein ◽  
Surface Proteins ◽  
Structural Basis ◽  
Content Type ◽  
Intrinsically Unstructured Protein ◽  
Unstructured Protein

ABSTRACTMerozoite surface protein 2 (MSP2) is an abundant glycosylphosphatidylinositol (GPI)-anchored protein ofPlasmodium falciparum, which is a potential component of a malaria vaccine. As all forms of MSP2 can be categorized into two allelic families, a vaccine containing two representative forms of MSP2 may overcome the problem of diversity in this highly polymorphic protein. Monomeric recombinant MSP2 is an intrinsically unstructured protein, but its conformational properties on the merozoite surface are unknown. This question is addressed here by analyzing the 3D7 and FC27 forms of recombinant and parasite MSP2 using a panel of monoclonal antibodies raised against recombinant MSP2. The epitopes of all antibodies, mapped using both a peptide array and by nuclear magnetic resonance (NMR) spectroscopy on full-length recombinant MSP2, were shown to be linear. The antibodies revealed antigenic differences, which indicate that the conserved N- and C-terminal regions, but not the central variable region, are less accessible in the parasite antigen. This appears to be an intrinsic property of parasite MSP2 and is not dependent on interactions with other merozoite surface proteins as the loss of some conserved-region epitopes seen using the immunofluorescence assay (IFA) on parasite smears was also seen on Western blot analyses of parasite lysates. Further studies of the structural basis of these antigenic differences are required in order to optimize recombinant MSP2 constructs being evaluated as potential vaccine components.

scholarly journals Construction of a tetR-Integrated Salmonella enterica Serovar Typhi CVD908 Strain That Tightly Controls Expression of the Major Merozoite Surface Protein of Plasmodium falciparum for Applications in Human Vaccine Production

2002 ◽  
Vol 70 (4) ◽  
pp. 2029-2038 ◽  
Author(s):  
Feng Qian ◽  
Weiqing Pan
Keyword(s):  
Plasmodium Falciparum ◽  
Vaccine Strain ◽  
Salmonella Enterica ◽  
Expression Vector ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Inducible Expression ◽  
Luciferase Reporter ◽  
Foreign Gene

ABSTRACT Attenuated Salmonella strains are an attractive live vector for delivery of a foreign antigen to the human immune system. However, the problem with this vector lies with plasmid segregation and the low level of expression of the foreign gene in vivo when constitutive expression is employed, leading to a diminished immune response. We have established inducible expressions of foreign genes in the Salmonella enterica serovar Typhi CVD908 vaccine strain using the tetracycline response regulatory promoter. To set up this system, a tetracycline repressor (tetR) was integrated into a defined ΔaroC locus of the chromosome via suicide plasmid pJG12/tetR-neo. To remove the neo gene conferring kanamycin resistance from the locus, a cre expression vector under the control of the tetracycline response promoter was transformed into the clone; expression of the Cre recombinase excised the neo gene and generated the end strain CVD908-tetR. Expression of the luciferase reporter gene in this strain is dependent on the presence of tetracycline in the medium and can be regulated up to 4,773-fold. Moreover, the tightly controlled expression of major merozoite surface protein 1 (MSP1) and parts of Plasmodium falciparum was achieved, and the product yield was increased when the inducible expression system was employed. Inoculation of bacteria harboring plasmid pZE11/MSP142 in mice produced the protein in liver and spleen controlled by the inducer. The persistence of the plasmid-carrying bacteria in mice was determined. Peak colonization of both liver and spleen was detected on the third day postinoculation and was followed by a decline in growth curves. After 14 days postinfection, the majority of the bacteria (>90%) recovered from the liver and spleen of the mice retained the plasmid when expression was induced; this clearly indicated that stability of the expression vector in vivo was improved by inducible expression. Establishment of the regulatory system in the vaccine strain may broaden the range of its use by enhancing plasmid stability and expression levels in vivo. Moreover, the availability of the vaccine strain inducibly expressing the entire MSP1 provides possibilities for examining its immunogenicity, particularly the cellular response in animal models.

scholarly journals Deletion of the Plasmodium falciparum Merozoite Surface Protein 7 Gene Impairs Parasite Invasion of Erythrocytes

2008 ◽  
Vol 7 (12) ◽  
pp. 2123-2132 ◽  
Author(s):  
Madhusudan Kadekoppala ◽  
Rebecca A. O'Donnell ◽  
Munira Grainger ◽  
Brendan S. Crabb ◽  
Anthony A. Holder
Keyword(s):  
Plasmodium Falciparum ◽  
Protein Interactions ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Significant Degree ◽  
Surface Proteins ◽  
Transcriptional Level ◽  
Parental Line ◽  
Parasite Line ◽  
Asexual Blood Stage

ABSTRACT Merozoite surface proteins have been implicated in the initial attachment to the host red blood cell membrane that begins the process of invasion, an important step in the life cycle of the malaria parasite. In Plasmodium falciparum, merozoite surface proteins include several glycosylphosphatidyl inositol-anchored proteins and peripheral proteins attached to the membrane through protein-protein interactions. The most abundant of these proteins is the merozoite surface protein 1 (MSP1) complex, encoded by at least three genes: msp1, msp6, and msp7. The msp7 gene is part of a six-member multigene family in Plasmodium falciparum. We have disrupted msp7 in the Plasmodium falciparum D10 parasite, as confirmed by Southern hybridization. Immunoblot and indirect immunofluorescence analyses confirmed the MSP7 null phenotype of D10ΔMSP7 parasites. The synthesis, distribution, and processing of MSP1 were not affected in this parasite line. The level of expression and cellular distribution of the proteins MSP1, MSP3, MSP6, MSP9, and SERA5 remained comparable to those for the parental line. Furthermore, no significant change in the expression of MSP7-related proteins, except for that of MSRP5, was detected at the transcriptional level. The lack of MSP7 was not lethal at the asexual blood stage, but it did impair invasion of erythrocytes by merozoites to a significant degree. Despite this reduction in efficiency, D10ΔMSP7 parasites did not show any obvious preference for alternate pathways of invasion.

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