Mapping of the region predominantly recognized by antibodies to the Plasmodium falciparum merozoite surface antigen MSA 1

Cooper, Juan A.; Cooper, Leanne; Saul, Allan

doi:10.1016/0166-6851(92)90080-4

Cited by 81 publications

(118 citation statements)

References 30 publications

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“…IgG Abs in mothers and their newborns recognized the Q-KNG as well as the E-KNG, Q-TSR, and E-TSR alleles, although Ab to the E-TSR variant was less than that observed to the other variants. This is consistent with the notion that Abs to MSP-1 19 bind to conformational epitopes conserved in the two epidermal growth factor motifs, i.e., binding is not constrained by changes in primary amino acid sequence that do not affect folding through disulfide bonds in cysteine residues (33,39,(62)(63)(64)(65). Similarly, cytokine responses in mothers and their newborns were stimulated equally well by each of the four constructs.…”

Section: Discussionsupporting

confidence: 74%

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Acquired Immune Responses to Plasmodium falciparum Merozoite Surface Protein-1 in the Human Fetus

King

Malhotra

Wamachi

et al. 2002

The Journal of Immunology

104

108

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Infants born in areas of stable malaria transmission are relatively protected against severe morbidity and high density Plasmodium falciparum blood-stage infection. This protection may involve prenatal sensitization and immunologic reactivity to malaria surface ligands that participate in invasion of red cells. We examined cord blood T and B cell immunity to P. falciparum merozoite surface protein-1 (MSP-1) in infants born in an area of stable malaria transmission in Kenya. T cell cytokine responses to the C-terminal 19-kDa fragment of MSP-1 (MSP-119) were detected in 24 of 92 (26%) newborns (4–192 IFN-γ and 3–88 IL-4-secreting cells per 106/cord blood lymphocytes). Peptide epitopes in the N-terminal block 3 region of MSP-1 also drove IFN-γ and/or IL-13 production. There was no evidence of prenatal T cell sensitization to liver-stage Ag-1. A total of 5 of 86 (6%) newborns had cord blood anti-MSP-119 IgM Abs, an Ig isotype that does not cross the placenta and is therefore of fetal origin. The frequency of neonatal B cell sensitization was higher than that indicated by serology alone, as 5 of 27 (18%) cord blood samples contained B cells that produced IgG when stimulated with MSP-119 in vitro. Neonatal B cell IgG responses were restricted to the Q-KNG allele of MSP-119, the major variant in this endemic area, whereas T cells responded to all four MSP-119 alleles evaluated. In utero sensitization to MSP-1 correlated with the presence of malaria parasites in cord blood (χ2 = 20, p < 0.0001). These data indicate that prenatal sensitization to blood-stage Ags occurs in infants born in malaria endemic areas.

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Section: Discussionsupporting

confidence: 74%

“…Several lines of evidence suggest that MSP-1 and MSP-1 19 may be efficacious in a malaria vaccine. mAbs to MSP-1 have been found to inhibit in vitro growth of parasites (33,34). Ab levels to MSP-1 19 correlate with age-related changes in the level of asexual parasitemia in some, but not all malaria endemic areas (35)(36)(37)(38)(39)(40)(41).…”

Section: Discussionmentioning

confidence: 99%

Acquired Immune Responses to Plasmodium falciparum Merozoite Surface Protein-1 in the Human Fetus

King

Malhotra

Wamachi

et al. 2002

The Journal of Immunology

104

108

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“…A major focus has been on synthetic peptides or recombinant proteins of cell surface antigens (2)(3)(4)(5)(6). However, this approach has not been highly effective, although immunization with native cell surface proteins purified from the erythrocytic stage parasite is known to confer significant protective immunity (7)(8)(9)(10). It is plausible that post-translational modifications play an important role in antigenicity.…”

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confidence: 99%

Glycosylphosphatidylinositol Anchors Represent the Major Carbohydrate Modification in Proteins of Intraerythrocytic Stage Plasmodium falciparum

Gowda

Gupta

Davidson

1997

Journal of Biological Chemistry

136

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The nature and extent of carbohydrate modification in intraerythrocytic stage Plasmodium falciparum proteins have been controversial. This study describes the characterization of the carbohydrates in intraerythrocytic P. falciparum proteins and provides an overall picture of the nature of carbohydrate modification in the parasite proteins. P. falciparum strains were metabolically labeled with radioactive sugar precursors and ethanolamine at different developmental stages. The individual parasite proteins separated on SDS-polyacrylamide gels and whole parasite cell lysates were analyzed for the carbohydrate moieties. The results established the following: 1) glycosylphosphatidylinositol (GPI) anchors represent the major carbohydrate modification in the intraerythrocytic stage P. falciparum proteins; 2) in contrast to previous reports, O-linked carbohydrates are either absent or present only at very low levels in the parasite; and 3) P. falciparum contains low levels of N-glycosylation capability. The amount of N-linked carbohydrates in whole parasite proteins is ϳ6% compared with the GPI anchors attached to proteins based on radioactive GlcN incorporated into the proteins.The glycan cores of multiple parasite protein GPI anchors are all similar, consisting of protein-ethanolamine-phosphate-(Man␣1-2)6Man␣1-2Man␣1-6Man␣1-4GlcN. The fourth Man residues distal to GlcN of the GPI anchor glycan cores contain unidentified substituents that are susceptible to conditions of nitrous acid deamination. This unusual structural feature may contribute to the reported pathogenic properties of the P. falciparum GPI anchors.Malaria, a life-threatening disease caused by parasitic protozoa of the genus Plasmodium, is a major health problem throughout the tropical and subtropical regions of the world. Among the four species that infect humans, Plasmodium falciparum is the most virulent. New approaches such as vaccine development and novel therapeutic agents are urgently needed due to the emergence of parasite strains resistant to chloroquine and other commonly used drugs (1).Vaccines based on antigens of the blood stage parasite are under intensive study. A major focus has been on synthetic peptides or recombinant proteins of cell surface antigens (2-6). However, this approach has not been highly effective, although immunization with native cell surface proteins purified from the erythrocytic stage parasite is known to confer significant protective immunity (7-10). It is plausible that post-translational modifications play an important role in antigenicity. Accordingly, a basic understanding of such modifications may assist in the development of effective vaccines.Glycosylation is an often extensive post-translational modification of eukaryotic proteins. Carbohydrate moieties of glycoproteins perform a variety of functions including modulation of immunological properties, receptor-ligand interactions, sorting and localization of proteins, cell adhesion, and cell-cell communication (11). In addition, they contribute to protein conform...

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“…The primary processing sites of PfMSP-1 [17] also exhibit this same general consensus sequence, except that the most C-terminal primary processing sites of PfMSP-1 lacks the strong negative tendency on the P% side of the proposed consensus sequence. However, alternative processing sites for this position, which perfectly match the consensus sequence, have been proposed [19]. In addition, some minor processing fragments have been sequenced [16] and these protease sites also show good, but imperfect, homology to the consensus sequence.…”

mentioning

confidence: 99%

An additional primary proteolytic processing site in merozoite surface protein-1 of Plasmodium berghei

Wiser

Toebe

Jennings

1997

Molecular and Biochemical Parasitology

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Mapping of the region predominantly recognized by antibodies to the Plasmodium falciparum merozoite surface antigen MSA 1

Cited by 81 publications

References 30 publications

Acquired Immune Responses to Plasmodium falciparum Merozoite Surface Protein-1 in the Human Fetus

Acquired Immune Responses to Plasmodium falciparum Merozoite Surface Protein-1 in the Human Fetus

Glycosylphosphatidylinositol Anchors Represent the Major Carbohydrate Modification in Proteins of Intraerythrocytic Stage Plasmodium falciparum

An additional primary proteolytic processing site in merozoite surface protein-1 of Plasmodium berghei

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