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Antibodies against merozoite surface protein (MSP)-1(19) are a major component of the invasion-inhibitory response in individuals immune to malaria.

O'Donnell RA, de Koning-Ward TF, Burt RA, Bockarie M, Reeder JC, Cowman AF, Crabb BS - J. Exp. Med. (2001)

Bottom Line: Inhibitory antibodies are found in the sera of malaria-immune individuals, however, the specificity of those that are important to this process is not known.By comparing this transfected line with parental parasites that differ only in MSP-1(19), we show that antibodies specific for this domain are a major component of the inhibitory response in P. falciparum-immune humans and P. chabaudi-immune mice.In some individual human sera, MSP-1(19) antibodies dominated the inhibitory activity.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology & Immunology and the Co-operative Research Centre for Vaccine Technology, University of Melbourne, VIC 3010, Australia.

ABSTRACT
Antibodies that bind to antigens expressed on the merozoite form of the malaria parasite can inhibit parasite growth by preventing merozoite invasion of red blood cells. Inhibitory antibodies are found in the sera of malaria-immune individuals, however, the specificity of those that are important to this process is not known. In this paper, we have used allelic replacement to construct a Plasmodium falciparum parasite line that expresses the complete COOH-terminal fragment of merozoite surface protein (MSP)-1(19) from the divergent rodent malaria P. chabaudi. By comparing this transfected line with parental parasites that differ only in MSP-1(19), we show that antibodies specific for this domain are a major component of the inhibitory response in P. falciparum-immune humans and P. chabaudi-immune mice. In some individual human sera, MSP-1(19) antibodies dominated the inhibitory activity. The finding that antibodies to a small region of a single protein play a major role in this process has important implications for malaria immunity and is strongly supportive of further understanding and development of MSP-1(19)-based vaccines.

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Invasion inhibition of transfected P. falciparum parasites expressing divergent MSP-119 domains by sera from clinically immune individuals reveals an important role for MSP-119–specific antibodies. (A) Assay 1, microscopy. Microscopy-based invasion inhibition assay involving the detection of ring-stage D10 and D10-PcMEGF (PcMEGF) parasites after cultivation in the presence of each individual serum. (B) Assay 2, hypoxanthine uptake. Alternative invasion-inhibition assay comparing D10-PfM3′ (PfM3′) and D10-PcMEGF parasites using [3H]hypoxanthine uptake as a measure of parasite growth. Invasion is represented as either parasitemia (A) or counts (B) and is expressed as a percentage of the invasion observed in parasites cultured in negative control sera (HNIS). The means of samples within a serum set against each parasite line are indicated. P values from a Student's t test comparing the means in each panel are shown.
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Figure 3: Invasion inhibition of transfected P. falciparum parasites expressing divergent MSP-119 domains by sera from clinically immune individuals reveals an important role for MSP-119–specific antibodies. (A) Assay 1, microscopy. Microscopy-based invasion inhibition assay involving the detection of ring-stage D10 and D10-PcMEGF (PcMEGF) parasites after cultivation in the presence of each individual serum. (B) Assay 2, hypoxanthine uptake. Alternative invasion-inhibition assay comparing D10-PfM3′ (PfM3′) and D10-PcMEGF parasites using [3H]hypoxanthine uptake as a measure of parasite growth. Invasion is represented as either parasitemia (A) or counts (B) and is expressed as a percentage of the invasion observed in parasites cultured in negative control sera (HNIS). The means of samples within a serum set against each parasite line are indicated. P values from a Student's t test comparing the means in each panel are shown.

Mentions: Preliminary experiments in our laboratory had indicated that D10-PcMEGF were relatively resistant to inhibition by human sera from malaria-immune individuals. To explore this more thoroughly, all PNG-M, PNG-B, and Pc-immune mouse sera were assessed for their ability to inhibit invasion of D10 and D10-PcMEGF merozoites in a microscopy-based invasion inhibition assay. All sera were tested in the one assay with the same parasite preparations (assay 1; Fig. 3 A). PNG-B sera were relatively effective at inhibiting invasion of parental D10 parasites with a mean invasion of 26.7%. PNG-M sera were generally less inhibitory of D10 parasites (43.1%). The difference between PNG-B and PNG-M sera, both in invasion-inhibition and total MSP-119 antibodies (Table ), may simply reflect a loss of potency of PNG-M sera over relatively long-term cryopreservation period (∼20 yr) although this was not explored further.


Antibodies against merozoite surface protein (MSP)-1(19) are a major component of the invasion-inhibitory response in individuals immune to malaria.

O'Donnell RA, de Koning-Ward TF, Burt RA, Bockarie M, Reeder JC, Cowman AF, Crabb BS - J. Exp. Med. (2001)

Invasion inhibition of transfected P. falciparum parasites expressing divergent MSP-119 domains by sera from clinically immune individuals reveals an important role for MSP-119–specific antibodies. (A) Assay 1, microscopy. Microscopy-based invasion inhibition assay involving the detection of ring-stage D10 and D10-PcMEGF (PcMEGF) parasites after cultivation in the presence of each individual serum. (B) Assay 2, hypoxanthine uptake. Alternative invasion-inhibition assay comparing D10-PfM3′ (PfM3′) and D10-PcMEGF parasites using [3H]hypoxanthine uptake as a measure of parasite growth. Invasion is represented as either parasitemia (A) or counts (B) and is expressed as a percentage of the invasion observed in parasites cultured in negative control sera (HNIS). The means of samples within a serum set against each parasite line are indicated. P values from a Student's t test comparing the means in each panel are shown.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2193299&req=5

Figure 3: Invasion inhibition of transfected P. falciparum parasites expressing divergent MSP-119 domains by sera from clinically immune individuals reveals an important role for MSP-119–specific antibodies. (A) Assay 1, microscopy. Microscopy-based invasion inhibition assay involving the detection of ring-stage D10 and D10-PcMEGF (PcMEGF) parasites after cultivation in the presence of each individual serum. (B) Assay 2, hypoxanthine uptake. Alternative invasion-inhibition assay comparing D10-PfM3′ (PfM3′) and D10-PcMEGF parasites using [3H]hypoxanthine uptake as a measure of parasite growth. Invasion is represented as either parasitemia (A) or counts (B) and is expressed as a percentage of the invasion observed in parasites cultured in negative control sera (HNIS). The means of samples within a serum set against each parasite line are indicated. P values from a Student's t test comparing the means in each panel are shown.
Mentions: Preliminary experiments in our laboratory had indicated that D10-PcMEGF were relatively resistant to inhibition by human sera from malaria-immune individuals. To explore this more thoroughly, all PNG-M, PNG-B, and Pc-immune mouse sera were assessed for their ability to inhibit invasion of D10 and D10-PcMEGF merozoites in a microscopy-based invasion inhibition assay. All sera were tested in the one assay with the same parasite preparations (assay 1; Fig. 3 A). PNG-B sera were relatively effective at inhibiting invasion of parental D10 parasites with a mean invasion of 26.7%. PNG-M sera were generally less inhibitory of D10 parasites (43.1%). The difference between PNG-B and PNG-M sera, both in invasion-inhibition and total MSP-119 antibodies (Table ), may simply reflect a loss of potency of PNG-M sera over relatively long-term cryopreservation period (∼20 yr) although this was not explored further.

Bottom Line: Inhibitory antibodies are found in the sera of malaria-immune individuals, however, the specificity of those that are important to this process is not known.By comparing this transfected line with parental parasites that differ only in MSP-1(19), we show that antibodies specific for this domain are a major component of the inhibitory response in P. falciparum-immune humans and P. chabaudi-immune mice.In some individual human sera, MSP-1(19) antibodies dominated the inhibitory activity.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology & Immunology and the Co-operative Research Centre for Vaccine Technology, University of Melbourne, VIC 3010, Australia.

ABSTRACT
Antibodies that bind to antigens expressed on the merozoite form of the malaria parasite can inhibit parasite growth by preventing merozoite invasion of red blood cells. Inhibitory antibodies are found in the sera of malaria-immune individuals, however, the specificity of those that are important to this process is not known. In this paper, we have used allelic replacement to construct a Plasmodium falciparum parasite line that expresses the complete COOH-terminal fragment of merozoite surface protein (MSP)-1(19) from the divergent rodent malaria P. chabaudi. By comparing this transfected line with parental parasites that differ only in MSP-1(19), we show that antibodies specific for this domain are a major component of the inhibitory response in P. falciparum-immune humans and P. chabaudi-immune mice. In some individual human sera, MSP-1(19) antibodies dominated the inhibitory activity. The finding that antibodies to a small region of a single protein play a major role in this process has important implications for malaria immunity and is strongly supportive of further understanding and development of MSP-1(19)-based vaccines.

Show MeSH
Related in: MedlinePlus