Characterization of Naturally Acquired Human IgG Responses against the N-Terminal Region of the Merozoite Surface Protein 1 of Plasmodium vivax

Levitus, Gabriela; Mertens, Frédéric; Sperança, Márcia Aparecida; Camargo, Luiz Octávio de Lima; Ferreira, Marcelo Urbano; Portillo, Hernando A. del

doi:10.4269/ajtmh.1994.51.68

Cited by 31 publications

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“…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). Primate vaccine trials (42,43) and studies of mouse malaria models indicate that immunization with MSP-1 19 (44,45) protects against blood-stage infection.…”

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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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: 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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“…Glutathione S-transferase (GST) fusion proteins representing the N terminus (ICB2-5; contains 505 amino acids [aa], corresponding to aa 170 to 675 from the original PvMSP1 molecule of the Belem strain [11]) and the C terminus (ICB10; contains 111 amino acids, corresponding to aa 1615 to 1726, and encodes the two epidermal growth factor-like domains of other MSP1 19 molecules) of PvMSP1 have already been described (19,34). GST and recombinant proteins were purified on glutathione-Sepharose 4B columns (Amersham Pharmacia), and protein concentration was determined by Bradford assay (Bio-Rad).…”

Section: Methodsmentioning

confidence: 99%

“…The presence of naturally acquired antibodies against GST-PvMSP1 tags has been described in detail elsewhere (19,34). To determine if a serum was positive, we calculated the cutoff for each recombinant protein representing the N terminus and the C terminus of PvMSP1 for each survey, using as negative controls individual sera from nine healthy individuals from Portuchuelo and three healthy individuals from elsewhere who never had a past history of malaria.…”

Section: Methodsmentioning

confidence: 99%

“…Thus, recombinant proteins representing conserved and polymorphic regions from the N terminus of PvMSP1 demonstrated that polymorphic, as opposed to conserved regions, of PvMSP1 are immunogenic in natural infections and that close to 50% of patients with multiple infections had an antibody response in which the predominant isotype was IgM (19,22). Studies including the C terminus of PvMSP1 followed and demonstrated that this region is the most immunogenic portion of the molecule, that the presence of antibodies against it is associated with recent malaria attacks, and that it is the only region of PvMSP1 capable of boosting upon new infections (34,35).…”

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confidence: 99%

“…MSP1 is a largemolecular-mass protein synthesized as a precursor and later processed into four major fragments of circa 83 kDa, 30 kDa, 38 kDa, and 42 kDa. A second specific processing step cleaves the 42-kDa C-terminal fragment into a 33-kDa polypeptide that is shed into circulation and a 19-kDa portion (MSP1 19 ) that remains attached to the newly formed ring stage parasite after invasion (16). Antibodies against different regions of MSP1 of P. falciparum (PfMSP1) are immunogenic in natural infections and are associated with reduced clinical symptoms.…”

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A Reduced Risk of Infection with Plasmodium vivax and Clinical Protection against Malaria Are Associated with Antibodies against the N Terminus but Not the C Terminus of Merozoite Surface Protein 1

et al. 2006

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Progress towards the development of a malaria vaccine against Plasmodium vivax, the most widely distributed human malaria parasite, will require a better understanding of the immune responses that confer clinical protection to patients in regions where malaria is endemic. The occurrence of clinical protection in P. vivax malaria in Brazil was first reported among residents of the riverine community of Portuchuelo, in Rondônia, western Amazon. We thus analyzed immune sera from this same human population to determine if naturally acquired humoral immune responses against the merozoite surface protein 1 of P. vivax, PvMSP1, could be associated with reduced risk of infection and/or clinical protection. Our results demonstrated that this association could be established with anti-PvMSP1 antibodies predominantly of the immunoglobulin G3 subclass directed against the N terminus but not against the C terminus, in spite of the latter being more immunogenic and capable of natural boosting. This is the first report of a prospective study of P. vivax malaria demonstrating an association of reduced risk of infection and clinical protection with antibodies against an antigen of this parasite.Malaria remains one of the major public health problems in South and Central America, where Plasmodium vivax is the main species responsible for infections. Although malaria caused by this human parasite is not lethal, the clinical manifestations represent a major socioeconomical burden in the major cities and rural areas of the Brazilian Amazon, which contains 99.7% of all malaria cases. Although a few studies indicate that some cross-protection between Plasmodium vivax, the most widely distributed human malaria parasite, and P. falciparum, the most virulent species, does occur (33), immunity in malaria is mostly species specific; thus, it is likely that a vaccine against P. falciparum will not cross-protect against P. vivax. Progress is being made to develop P. vivax vaccines per se (for a review, see reference 2); however, to date there are no prospective studies associating human immune responses to any P. vivax antigen with clinical protection.The history of malaria in Brazil has been punctuated with epidemics associated with migration movements of nonimmune population to areas where malaria is endemic (20,30,36). Previous studies done in these epidemiological settings showed that Plasmodium infection was always associated with symptoms, and clinical protection was not observed (27). However, through a cross-sectional and longitudinal study among native Amazon residents of the riverine community of Portuchuelo in Rondônia, located in the western Brazilian Amazon, the occurrence of symptomless Plasmodium vivax-infected individuals was reported (1, 6). Symptomless Plasmodium infections were defined as individuals who contain parasites in their peripheral blood, as detected by Giemsa blood smears and/or PCR, and who were not drug treated yet did not develop clinical symptoms during a 2-month individual follow-up. These rigorous criteria...

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Biochemical and Immunological Properties of a Viral Hybrid Particle Expressing the Plasmodium vivax Merozoite Surface Protein 1 C-terminal Region

Wunderlich

Portillo

2000

Mol Med

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most solid subunit vaccine candidates against the asexual blood stages of malaria, although its function remains elusive (1). Experiments in rodents, Aotus and Saimiri monkeys, either with the affinity-purified, yeast-, bacteria-or cell culturederived MSP1 19 , showed protection against blood stage challenge with P. falciparum (2), P. vivax (3), P. cynomolgi (4), and P. yoelii (5). Recently, a phase 1 clinical trial was reported (6). Since protection is mostly antibody-dependent (1),

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Characterization of Naturally Acquired Human IgG Responses against the N-Terminal Region of the Merozoite Surface Protein 1 of Plasmodium vivax

Cited by 31 publications

References 0 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

A Reduced Risk of Infection with Plasmodium vivax and Clinical Protection against Malaria Are Associated with Antibodies against the N Terminus but Not the C Terminus of Merozoite Surface Protein 1

Biochemical and Immunological Properties of a Viral Hybrid Particle Expressing the Plasmodium vivax Merozoite Surface Protein 1 C-terminal Region

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