Processing, polymorphism, and biological significance of P190, a major surface antigen of the erythrocytic forms of Plasmodium falciparum

Hall, Roger; Osland, Arve; Hyde, John E.; Simmons, David Li.; Hope, Ian A.; Scaife, John

doi:10.1016/0166-6851(84)90055-0

Cited by 78 publications

(29 citation statements)

References 31 publications

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“…The difference in frequencies of antigen-specific antibody production observed in these two studies may be related to the different malaria-transmission rates and consequent differences in exposure to malaria antigens ofthe two regions. Prevalent antibody responses to purified gp195 (P190) also have been observed for sera of pregnant Nigerian women living in malaria-endemic regions (28).…”

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confidence: 99%

“…Effects of H-2 haplotype on antibody specificity have been reported for several model protein antigens (23)(24)(25) and for the hepatitis B surface antigen (26). Immunoblot analysis of P. falciparum lysates electrophoresed under nonreducing conditions revealed a complex pattern of reactivity with the gp195 precursor and a collection of smaller fragments thought to represent distinct regions of the complete molecule (27)(28)(29)(30)(31). It was of interest that the immunoblot complexity of all mouse strains was decreased when parasite lysates were electrophoresed under reducing conditions.…”

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Generalized immunological recognition of the major merozoite surface antigen (gp195) of Plasmodium falciparum.

Chang

Hui²,

Kato³

et al. 1989

Proc. Natl. Acad. Sci. U.S.A.

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The antibody response to the Plasmodium falciparum major merozoite surface antigen (gp195) of congenic mouse strains differing in H-2 haplotype has been examined. AU seven strains of mice were capable of producing gp195-specific antibodies. Generalized immune recognition of gp195 by mice of diverse H-2 haplotypes distinguished gp195 from the P. falciparum circumsporozoite protein and the 230-kDa and 48/45-kDa gamete surface antigens. However, the H-2 genetic locus appeared to influence the specificity of gp195-speciflic antibodies. Immunoblot patterns of mouse sera with parasite antigens revealed a complex pattern of reactivity with terminal and intermediate processing fragments of gp195. The majority of immunoblot bands observed were similar for all of the mouse strains; however, there were several strains that additionally recognized a few unique fragments or displayed more intense reactivities with specific processing fragments. These results suggest that while individuals of diverse major histocompatibility complex makeup are capable of recognizing the gp195 antigen, the recognition of specific gp195B-cell and T-cell epitopes may be under control of the major histocompatibility complex.The global resurgence of malaria, which is due in part to the spread of drug-resistant Plasmodium falciparum and the reduced efficacy of vector control measures, has intensified efforts to develop a malaria vaccine (1, 2). The current subunit vaccine strategy for producing a malaria vaccine relies on the ability of single parasite antigens to confer protective immunity in animal models or to induce antibodies that inhibit parasite growth in vitro (3). Antigens expressed during several stages of the complex life cycle of P. In toto, these results have profound implications for development of subunit malaria vaccines. In order to be effective, a vaccine must stimulate an immune response in individuals of diverse genetic makeup. If widespread, genetically controlled nonresponsiveness is a common characteristic of malaria antigens, the feasibility of the subunit vaccine strategy will be severely compromised.While genetic control of immune responsiveness to certain malaria antigens of the sexual stages of the parasite life cycle has been demonstrated, the effect of major histocompatibility complex (MHC) genes on responsiveness to asexual bloodstage antigens has not been examined. A prime candidate antigen for the development ofimmunity to the asexual blood stages ofP. falciparum is the major merozoite surface protein (gp195), whose processing fragments are found on the surface of the infective merozoite (9). Several laboratories including our own have shown that vaccination of monkeys with purified gp195 or its processing fragments protects these animals against a lethal challenge dose of P. falciparum (10)(11)(12)(13). In addition, a limited clinical trial with synthetic peptides containing gp195-related amino acid sequences has produced promising results (14). Therefore, it is important to determine whether immune respons...

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confidence: 99%

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confidence: 99%

Generalized immunological recognition of the major merozoite surface antigen (gp195) of Plasmodium falciparum.

Chang

Hui²,

Kato³

et al. 1989

Proc. Natl. Acad. Sci. U.S.A.

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“…The major P. falciparum merozoite surface-coat proteins are the 83-, 42-, and 19-kDa processing fragments (6) derived from a glycosylated, polymorphic precursor molecule having a variable molecular mass of [185][186][187][188][189][190][191][192][193][194][195][196][197][198][199][200] kDa, depending on the strain studied (7)(8)(9)(10)(11)(12)(13)(14)(15). Immunization with the mAb-isolated precursor protein and its processing fragments (2) or with the precursor protein alone, isolated by preparative NaDodSO4/ PAGE (3), partially protects Saimiri (squirrel) monkeys against heterologous challenge and indicates that conserved, nonpolymorphic regions may have vaccine potential.…”

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Merozoite surface coat precursor protein completely protects Aotus monkeys against Plasmodium falciparum malaria.

Siddiqui¹,

Tam²,

Kramer³

et al. 1987

Proc. Natl. Acad. Sci. U.S.A.

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Groups of Aotus (owl) monkeys were immunized with either the Plasmodiumfalciparum merozoite surfacecoat precursor protein and its processing fragments or a complex of high molecular mass rhoptry proteins and challenged with a lethal infection of the homologous P. falciparum Uganda Palo Alto (FUP) strain. No patent parasitemia could be detected on thick blood films of monkeys immunized with the merozoite surface antigens; however, only one of three monkeys immunized with the rhoptry proteins was partially protected, while two required drug therapy. The experiment clearly demonstrates that the merozoite surface-coat precursor protein can completely protect Aetus monkeys against a lethal infection of the human malaria parasite.

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“…Some of the antigen genes like the RESA gene (11) and the P. falciparum circumsporozoite protein gene (12) appear to be conserved in sequence between strains, while others like the S antigen gene (13) vary. One P. falciparum antigen which has been studied in considerable detail is a merozoite surface glycoprotein of about 195,000 molecular weight (gp195) (14)(15)(16)(17)(18)(19)(20). This large antigen is processed about the time of erythrocyte rupture into several smaller species which are also located at the merozoite surface.…”

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confidence: 99%

Variation in the gene encoding a major merozoite surface antigen of the human malaria parasitePlasmodium falciparum

1986

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Plasmodium falciparum merozoites have a variable surface protein of about 195,000 molecular weight which may be involved in strain-specific immunity. We have cloned and sequenced a major portion of the gene encoding this antigen from the CAMP strain and have located sites of preferred mung bean nuclease cleavage around the gene. These sites depend on reaction conditions, but at 40% formamide and 2 units of mung bean nuclease per pg DNA, the intact gene was excised from the chromosome. Comparison of the CAMP strain gene with the same gene from other strains of P. falciparum by matching available DNA sequences and by DNA hybridization revealed five regions of homology separated by divergent segments. Two of the variable regions encoded three amino acid repeats, predominantly Ser-Gly-Thr and ThrGlu-Glu. Implications of these findings on the function of the antigen, and possible mechanisms for generation of variants are discussed.

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Processing, polymorphism, and biological significance of P190, a major surface antigen of the erythrocytic forms of Plasmodium falciparum

Cited by 78 publications

References 31 publications

Generalized immunological recognition of the major merozoite surface antigen (gp195) of Plasmodium falciparum.

Generalized immunological recognition of the major merozoite surface antigen (gp195) of Plasmodium falciparum.

Merozoite surface coat precursor protein completely protects Aotus monkeys against Plasmodium falciparum malaria.

Variation in the gene encoding a major merozoite surface antigen of the human malaria parasitePlasmodium falciparum

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