Antibodies to a Recombinant Glutamate-Rich Plasmodium Falciparum Protein: Evidence for Protection of Individuals Living in a Holoendemic Area of Liberia

Høgh, Birthe; Petersen, Eskild; Dziegiel, Morten Hanefeld; Koffi, David; Hanson, Aloysius P.; Borre, Martin B.; Holm, August; Vuust, Jens; Jepsen, Søren

doi:10.4269/ajtmh.1992.46.307

Cited by 34 publications

(26 citation statements)

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“…An association between high titers of GLURP-specific IgG and low parasite counts has been reported elsewhere [7]. Our data point to R0 and R2 as the regions of GLURP that are most important for protective efficacy.…”

Section: Discussionsupporting

confidence: 52%

“…Our data point to R0 and R2 as the regions of GLURP that are most important for protective efficacy. Although levels and prevalence of GLURP-specific IgM and IgG increase with age [7,8], the age compositions of our groups of protected and susceptible children were similar. Logistic-regression models taking the effect of age into consideration consistently identified IgG-in particular, IgG1 and IgG3-as a strong predictor of protection.…”

Section: Discussionmentioning

confidence: 60%

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Naturally Acquired Antibodies to the Glutamate‐Rich Protein Are Associated with Protection againstPlasmodium falciparumMalaria

et al. 2000

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The development of effective malaria vaccines depends on the identification of targets of well-defined protective immune responses. Data and samples from a longitudinal study of a cohort of children from coastal Ghana were used to investigate the role of antibody responses to 3 regions of the Plasmodium falciparum glutamate-rich protein (GLURP). The data show that levels of the GLURP-specific IgG that occurs in the nonrepeat region of the antigen are significantly correlated with clinical protection from P. falciparum malaria, after correction for the confounding effect of age. Furthermore, levels of cytophilic antibodies were found to be of particular importance for protection, lending support to the hypothesis that antibody-dependent cellular inhibition is the important element in GLURP-specific protective immunity.

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Section: Discussionsupporting

confidence: 52%

Section: Discussionmentioning

confidence: 60%

Naturally Acquired Antibodies to the Glutamate‐Rich Protein Are Associated with Protection againstPlasmodium falciparumMalaria

et al. 2000

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“…Immunoepidemiological studies have demonstrated a high prevalence of antibodies against recombinant GLURP fragments in adults from Liberia (20) and have shown that GLURPspecific IgG was associated with low parasite densities (10,11) and the absence of disease (8) in West African children.…”

mentioning

confidence: 99%

Cytophilic Immunoglobulin Responses toPlasmodium falciparumGlutamate-Rich Protein Are Correlated with Protection against Clinical Malaria in Dielmo, Senegal

et al. 2000

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The goal of this study was to analyze antibody responses to Plasmodium falciparum glutamate-rich protein (GLURP) using clinical data and plasma samples obtained from villagers of Dielmo, Senegal. This molecule was chosen because it is targeted by human antibodies which induce parasite growth inhibition in antibodydependent cellular inhibition (ADCI) assays. The results showed a strong correlation between protection against malaria attacks and levels of immunoglobulin G2 (IgG2) and IgG3 against GLURP 94-489 (R0) and IgG3 against GLURP 705-1178 (R2) when corrected for the confounding effect of age-related exposure to malaria. Thus, GLURP may play a role in the induction of protective immunity against P. falciparum malaria.Individuals repeatedly exposed to Plasmodium falciparum malaria infections gradually develop clinical immunity. Results from studies performed in vivo suggest that one of the mechanisms underlying clinical immunity to malaria is the containment of parasite multiplication by antibodies (12,13,15). It is reasonable to assume that if protective effects are mediated by antibodies, there is a relationship between the level, isotype, or function of the antibodies and the clinical outcome. Studies of the role of subclass responses in naturally developing clinical immunity to defined malaria antigens and fragments thereof are therefore important. Bouharoun-Tayoun and Druilhe found profound differences in the distribution of immunoglobulin (Ig) subclasses between clinically protected and nonprotected individuals, with cytophilic isotypes (IgG1 and IgG3) being dominant in protected individuals (5). This observation was later confirmed by Aribot (1), who found that the level of parasitespecific IgG3, but not total IgG, was inversely proportional to susceptibility to clinical malaria. In a study of severe malaria, Sarthou et al. demonstrated that only levels of P. falciparumspecific IgG3 were positively correlated with survival (16).The glutamate-rich protein (GLURP) of P. falciparum is synthesized during all stages of the parasite in the vertebrate host, including on the surface of newly released merozoites (2). Immunoepidemiological studies have demonstrated a high prevalence of antibodies against recombinant GLURP fragments in adults from Liberia (20) and have shown that GLURPspecific IgG was associated with low parasite densities (10, 11) and the absence of disease (8) in West African children.Motivated by these results and our recent findings that highly affinity-purified human IgG antibodies to GLURP were able to promote a strong monocyte-dependent inhibition of P. falciparum growth in vitro (19), we have investigated the distribution of isotypes to nonrepetitive and repetitive regions of GLURP in plasma from 214 villagers in Dielmo, Senegal, and its correlation to clinical protection.

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“…In this context, several proteins have been identified and selected as candidate molecules for use in the composition of a malaria vaccine. Among these, the P. falciparum glutamate-rich protein (GLURP) appears to be a promising candidate (Hogh et al 1992, Dziegiel et al 1993, Theisen et al 1998, Pratt-Riccio et al 2005.…”

mentioning

confidence: 99%

“…GLURP contains an Nterminal non-repeat region (R0), a central non-repeat region (R1) and a C-terminal repeat region (R2). Immunoepidemiological studies performed in high transmission areas have demonstrated a high prevalence of antibodies (GI) against GLURP in immune adults (Boudin et al 1993, Dziegiel et al 1993) and have shown that high levels of GLURP-specific antibodies are significantly associated with low parasite densities (Hogh et al 1992(Hogh et al , 1993 and protection against clinical malaria (Dziegiel et al 1993, Dodoo et al 2000. Moreover, GLURP is a target antigen for antibodies involved in antibody-dependent cellular inhibition (ADCI) (Theisen et al 1998), which is believed to be involved in acquired protective immunity against malaria (Khusmith & Druilhe 1983, Lunel & Druilhe 1989, Bouharoun-Tayoun et al 1990, Bouharoun-Tayoun & Druilhe 1992.…”

mentioning

confidence: 99%

Antibodies against the Plasmodium falciparum glutamate-rich protein from naturally exposed individuals living in a Brazilian malaria-endemic area can inhibit in vitro parasite growth

Pratt-Riccio¹,

Bianco‐Júnior²,

Totino³

et al. 2011

Mem. Inst. Oswaldo Cruz

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Antibodies to a Recombinant Glutamate-Rich Plasmodium Falciparum Protein: Evidence for Protection of Individuals Living in a Holoendemic Area of Liberia

Cited by 34 publications

References 0 publications

Naturally Acquired Antibodies to the Glutamate‐Rich Protein Are Associated with Protection againstPlasmodium falciparumMalaria

Naturally Acquired Antibodies to the Glutamate‐Rich Protein Are Associated with Protection againstPlasmodium falciparumMalaria

Cytophilic Immunoglobulin Responses toPlasmodium falciparumGlutamate-Rich Protein Are Correlated with Protection against Clinical Malaria in Dielmo, Senegal

Antibodies against the Plasmodium falciparum glutamate-rich protein from naturally exposed individuals living in a Brazilian malaria-endemic area can inhibit in vitro parasite growth

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