scholarly journals Plasmodium falciparum Merozoite Surface Protein 8 Is a Ring-Stage Membrane Protein That Localizes to the Parasitophorous Vacuole of Infected Erythrocytes

2005 ◽  
Vol 73 (7) ◽  
pp. 3912-3922 ◽  
Author(s):  
Damien R. Drew ◽  
Paul R. Sanders ◽  
Brendan S. Crabb
Keyword(s):  
Plasmodium Falciparum ◽  
Parasitophorous Vacuole ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Food Vacuole ◽  
Ring Stage ◽  
C Terminus ◽  
Falciparum Merozoite ◽  
Merozoite Antigens ◽  
Epidermal Growth

ABSTRACT To date, the following seven glycosylphosphatidylinositol (GPI)-anchored merozoite antigens have been described in Plasmodium falciparum: merozoite-associated surface protein 1 (MSP-1), MSP-2, MSP-4, MSP-5, MSP-8, MSP-10, and the rhoptry-associated membrane antigen. Of these, MSP-1, MSP-8, and MSP-10 possess a double epidermal growth factor (EGF)-like domain at the C terminus, and these modules are considered potential targets of protective immunity. In this study, we found that surprisingly, P. falciparum MSP-8 is transcribed and translated in the ring stage and is absent from the surface of merozoites. MSP-8 is the only GPI-anchored protein known to be expressed at this time. It is synthesized as a mature 80-kDa protein which is rapidly processed to a C-terminal 17-kDa species that contains the double EGF module. As determined by a combination of immunofluorescence and membrane purification approaches, it appears likely that MSP-8 initially localizes to the parasite plasma membrane in the ring stage. Although the C-terminal 17-kDa fragment is present in more mature stages, at these times it is found in the food vacuole. We successfully disrupted the MSP-8 gene in P. falciparum, a process that validated the specificity of the antibodies used in this study and also demonstrated that MSP-8 does not play a role essential to maintenance of the erythrocyte cycle. This finding, together with the observation that MSP-8 is exclusively intracellular, casts doubt over the viability of this antigen as a vaccine. However, it is still possible that MSP-8 is involved in an early parasitophorous vacuole function that is significant for pathogenesis in the human host.

scholarly journals Plasmodium falciparum Merozoite Surface Protein 6 Displays Multiple Targets for Naturally Occurring Antibodies That Mediate Monocyte-Dependent Parasite Killing

2005 ◽  
Vol 73 (2) ◽  
pp. 1235-1238 ◽  
Author(s):  
Subhash Singh ◽  
Soe Soe ◽  
Christian Roussilhon ◽  
Giampietro Corradin ◽  
Pierre Druilhe
Keyword(s):  
Plasmodium Falciparum ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Naturally Occurring ◽  
C Terminus ◽  
Sequence Homologies ◽  
Merozoite Surface Antigen ◽  
Falciparum Merozoite ◽  
Erythrocytic Cycle ◽  
Naturally Occurring Antibodies

ABSTRACT Plasmodium falciparum MSP6 is a merozoite surface antigen that shows organization and sequence homologies similar to those of MSP3. Within its C-terminus conserved region, it presents some epitopes that are cross-reactive with MSP3 and others that are not, both being targets of naturally occurring antibodies that block the P. falciparum erythrocytic cycle in cooperation with monocytes.

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 Fine Specificity of Serum Antibodies to Plasmodium falciparum Merozoite Surface Protein, PfMSP-119, Predicts Protection from Malaria Infection and High-Density Parasitemia

2004 ◽  
Vol 72 (3) ◽  
pp. 1557-1567 ◽  
Author(s):  
Brenda A. Okech ◽  
Patrick H. Corran ◽  
James Todd ◽  
Amy Joynson-Hicks ◽  
Chairat Uthaipibull ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Surface Protein ◽  
Field Studies ◽  
Merozoite Surface Protein ◽  
High Density ◽  
Enzyme Linked Immunosorbent Assay ◽  
Fine Specificity ◽  
Vaccine Trials ◽  
C Terminus ◽  
Falciparum Merozoite

ABSTRACT Antibodies to the C terminus of the Plasmodium falciparum merozoite surface protein, PfMSP-119, may inhibit merozoite invasion or block the effects of inhibitory antibodies. Here, using a competition enzyme-linked immunosorbent assay and antibody binding to wild-type and mutated recombinant proteins, we show that there are marked variations between individuals in the fine specificity of naturally acquired anti-MSP-119 antibodies. Furthermore, although neither the prevalence nor the concentration of total anti-MSP-119 antibodies was associated with resistance to malaria in African children, significant associations were observed between antibody fine specificity and subsequent risk of infection and high-density parasitemia during a follow-up period. Thus, the fine specificity of naturally acquired human anti-MSP-119 antibodies is crucial in determining their function. Future field studies, including the evaluation of PfMSP-1 vaccine trials, should include assays that explore antibody fine specificity as well as titer.

scholarly journals Immunogenicity and Efficacy in Aotus Monkeys of Four Recombinant Plasmodium falciparum Vaccines in Multiple Adjuvant Formulations Based on the 19-Kilodalton C Terminus of Merozoite Surface Protein 1

2000 ◽  
Vol 68 (4) ◽  
pp. 2215-2223 ◽  
Author(s):  
Sanjai Kumar ◽  
William Collins ◽  
Andrea Egan ◽  
Anjali Yadava ◽  
Olivier Garraud ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Protective Efficacy ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
C Terminus ◽  
Epidermal Growth ◽  
Freund’S Adjuvant ◽  
Freund's Adjuvant ◽  
Major Surface ◽  
High Degree

ABSTRACT The immunogenicity and protective efficacy of four versions of recombinant C-terminal 19-kDa epidermal growth factor-like region of the major surface protein 1 (rMSP119) of Plasmodium falciparum was studied in Aotus monkeys. Vaccination with each of the four rMSP119 constructs elicited high levels of antibodies to MSP119 but only one construct, the 19-kDa fragment expressed as a secreted fusion protein fromSaccharomyces cerevisiae (yP30P2MSP119), induced a high degree of protective immunity in Aotus nancymai against lethal P. falciparum challenge. Protective formulation required Freund's adjuvant; vaccination with yP30P2MSP119 in six other adjuvants that are suitable for human use induced lower levels of antibody response and no protection. These results emphasize the need to continue the search for an adjuvant that is comparable to Freund's adjuvant in potency and is safe for use in humans.

scholarly journals Plasmodium falciparum merozoite surface protein 2 is unstructured and forms amyloid-like fibrils

2009 ◽  
Vol 166 (2) ◽  
pp. 159-171 ◽  
Author(s):  
Christopher G. Adda ◽  
Vince J. Murphy ◽  
Margaret Sunde ◽  
Lynne J. Waddington ◽  
Jesse Schloegel ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Falciparum Merozoite
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