Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0024530 (malaria)
44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Merozoite surface protein 6 (MSP6) and 7 (MSP7) of Plasmodium falciparum are peripheral membrane proteins whose cleaved products, MSP636, MSP722 and MSP719, are found on the merozoite surface as components of a non-covalently bound complex which also contains four polypeptides derived from merozoite surface protein 1 (MSP1). We have expressed both the precursor regions and the processed mature products of MSP6 and MSP7 in Escherichia coli and showed that these recombinant proteins react with human immune sera. In a set of sera collected from individuals living in malaria-endemic areas of Southern-central Vietnam, antibodies to the mature polypeptides of MSP636 and MSP722 were detected in 50.6 and 85.6% of the serum samples, whereas antibodies to the precursor regions of MSP6 and MSP7 were detected in only 12.1 and 42.5% of the serum samples, respectively. The predominant subclass of anti-MSP6 antibodies was IgG1, whereas the predominant subclass of anti-MSP7 antibodies was IgG3. In the same set of serum samples, the antibody responses to MSP119 are predominantly IgGI, whereas antibodies to merozoite surface protein 4 (MSP4) are mainly IgG3. This data is consistent with the proposition that, during malaria infection, variable proteins induce responses that are predominantly of the IgG3 isotype, and conserved proteins induce responses that are predominantly IgG1. The antibodies to MSP6, MSP7 and MSP119 all decreased at the time of infection, but increased during the convalescent period. No correlation was observed between the antibodies at the commencement of the study and absence of parasitaemia during surveillance in this population.
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PMID:Naturally acquired antibody responses to the components of the Plasmodium falciparum merozoite surface protein 1 complex. 1465 87

We assessed immunoglobulin G (IgG) isotype responses with specificity for the variant surface antigens (VSA) of heterologous Plasmodium falciparum isolates by using flow cytometry and plasma from healthy Gabonese adults and from children during and after two consecutive malaria episodes. The individual isolate-specific antibody profiles differed markedly in terms of their isotype content but were similar for healthy adults and healthy uninfected children. In healthy adults, IgG3 and IgG2 responses were the highest, while in healthy children, IgG3 and IgG4 predominated. A transiently elevated IgG1 response was observed during the second of two successive malaria episodes in children, signaling P. falciparum infection-induced cross-reactive anti-VSA responses. Our findings highlight the prominence of IgG3 in the overall profile of these responses but also indicate a marked age-related increase in the prevalence of anti-VSA antibodies of the classically noncytophilic IgG2 isotype, possibly reflecting the high frequency of the histidine-131 variant of FcgammaRIIA in the Gabonese population.
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PMID:Immunoglobulin G isotype responses to variant surface antigens of Plasmodium falciparum in healthy Gabonese adults and children during and after successive malaria attacks. 1468 7

Rhoptry proteins participate in the invasion of red blood cells by merozoites during the malaria parasite's asexual-stage cycle. Interference with the rhoptry protein function has been shown to prevent invasion, and three rhoptry proteins have been suggested as potential components of a vaccine against malaria. Rhoptry-associated membrane antigen (RAMA) is a 170-kDa protein of Plasmodium falciparum which is processed to a 60-kDa mature form in the rhoptries. p60/RAMA is discharged from rhoptries of free merozoites and binds to the red-cell membrane before being internalized to form part of the parasitophorous vacuole of the newly developing ring. We examined the range of anti-RAMA responses in individuals living in an area of endemicity for malaria and determined its association with clinical immunity. RAMA is immunogenic during infections, and at least three epitopes within RAMA are recognized by hyperimmune sera in immunoblots. Sera from individuals living in a region of Vietnam where malaria is endemic possessed strong antibody responses toward two C-terminal regions of RAMA. Cytophilic antibody isotypes (immunoglobulin G1 [IgG1] and IgG3) predominated in humoral responses to both C-terminal epitopes. Acute episodes of P. falciparum infection result in significant boosting of levels of antibody to an epitope at the extreme C terminus of RAMA that harbors the red-cell-binding domain. Immunity to P. falciparum infection was linked to elevated levels of IgG3 responses to this functional domain of RAMA, suggesting that the region may contain a protective epitope useful for inclusion in a multiepitope vaccine against malaria.
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PMID:Associations between responses to the rhoptry-associated membrane antigen of Plasmodium falciparum and immunity to malaria infection. 1515 36

The ability of Plasmodium falciparum to induce long-term immunity in the absence of continual restimulation has often been questioned. Recently it has been shown that, while a high proportion of individuals living in areas of high malaria endemicity have antibodies to merozoite surface antigen 2 (MSA2; MSP2) of P. falciparum, these antibodies are primarily of the IgG3 subclass. In this article, Antonio Ferrante and Christine Rzepczyk discuss how such atypical antibody responses may in part explain why immunity to malaria has been widely perceived to be short-lived.
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PMID:Atypical IgG subclass antibody responses to Plasmodium falciparum asexual stage antigens. 1527 1

The 42- and 19-kDa C-terminal fragments of merozoite surface protein 1 (MSP-1(42) and MSP-1(19), respectively) are both promising blood-stage vaccine candidate antigens. At present, it is not clear which of the two antigens will be more suitable for inclusion in a cocktail malaria vaccine. In the present study, we expressed the two C-terminal fragments of Plasmodium vivax MSP-1 (PvMSP-1) in an Escherichia coli expression system and purified them by using a rapid two-step protocol. Both of the products were recognized by monoclonal antibodies against PvMSP-1 as well as by immune sera from several individuals exposed to P. vivax. We analyzed and compared the immunological responses to recombinant PvMSP-1(19) and PvMSP-1(42) in mice by using six different adjuvant formulations. Moderate to high antibody responses were observed with both of the antigens in different adjuvant formulations. Surprisingly, alum, which is generally considered to be a poor adjuvant for recombinant malaria antigens, was found to be as good an adjuvant as Montanide ISA 720, ASO2A, and other adjuvant formulations. Most adjuvant formulations induced high levels of immunoglobulin G1 (IgG1), followed by IgG3 and IgG2. Lymphocytes from animals in the PvMSP-1(42)- and PvMSP-1(19)-immunized groups showed proliferative responses upon stimulation with the respective antigens, and high levels of interleukin-4 (IL-4), IL-5, and gamma interferon were detected in the culture supernatants. Immunodepletion studies with sera from mice immunized with these two antigens showed that while immunization with PvMSP-1(42) does produce a PvMSP-1(19)-specific response, a substantial portion is also focused on structures in PvMSP-1(42) not represented by the epidermal growth factor-like domains of PvMSP-1(19). These findings may have implications for the design of MSP-1-based vaccine constructs.
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PMID:Comparison of immunogenicities of recombinant Plasmodium vivax merozoite surface protein 1 19- and 42-kiloDalton fragments expressed in Escherichia coli. 1538 77

The merozoite surface protein-1 (MSP-1) of Plasmodium falciparum comprises two major targets of antibody-mediated immunity: the polymorphic block 2 and the 19-kDa C-terminal domain MSP-1(19). Here, we measured antibodies to three block 2 variants and MSP-1(19) among Amazonian gold miners and examined the repertoire of block 2 variants in local parasites. Main findings were as follows: (1) Only seven different block 2 variants were found in 18 DNA sequences analyzed. (2) No major difference was observed in IgG subclass distribution of antibodies from symptomatic P. falciparum-infected patients, asymptomatic parasite carriers, and non-infected subjects. (3) Antibodies to all block 2 antigens, but not to MSP-1(19), were biased towards IgG3 across different strata of cumulative malaria exposure. (4) Similar proportions of symptomatic and asymptomatic subjects failed to recognize the block 2 variant expressed by infecting parasites. These negative results underscore the limits of conventional antibody assays to evaluate clinical immunity to malaria.
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PMID:Plasmodium falciparum: IgG subclass antibody response to merozoite surface protein-1 among Amazonian gold miners, in relation to infection status and disease expression. 1568 19

Subclasses of antibodies to the C-terminal 19 kDa fragment of the Plasmodium vivax merozoite surface protein 1 (PvMSP-1(19)) were assessed among subjects with distinct degrees of malaria exposure in the Brazilian endemic area. The PvMSP-1(19) specific IgG1and IgG3 levels were low among subjects with long-term exposure (approximately 19 years) when compared to subjects less and sporadically exposed (<1 year). No statistically difference was observed in IgG subclass distribution of antibodies from symptomatic Plasmodium-infected patients, asymptomatic parasite carriers and non-infected subjects living in a same mesoendemic area. Subjects briefly exposed to a P. vivax outbreak living in a rural community outside the endemic area were also evaluated to measure the persistence of specific antibodies. IgG anti-PvMSP-1(19) antibodies persisted in 40% of the subjects who had had malarial symptoms 8 months before and decreased after 7 years (28%). Specific IgG1 were the predominant isotype. Our study emphasizes the highly immunogenicity of the PvMSP-1(19) and points toward its possible use as a potential malaria vaccine.
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PMID:IgG isotype to C-terminal 19 kDa of Plasmodium vivax merozoite surface protein 1 among subjects with different levels of exposure to malaria in Brazil. 1575 56

We assessed immunoglobulin G (IgG) isotype responses to variant surface antigens (VSA) expressed on parasite-infected erythrocytes of a panel of heterologous isolates during and after acute episodes in groups of Gabonese children presenting with either mild or severe Plasmodium falciparum malaria. In the acute and convalescent phases IgG3 and IgG1 anti-VSA antibodies, respectively, predominated. In the absence of infection, the levels of both cytophilic isotypes waned, while those of IgG4 increased, particularly in those admitted with severe malaria. Prospective analyses showed significantly longer delays between malaria attacks associated both (i) with increasing IgG1 responses with specificity for VSA of isolates from children with mild malaria and (ii) with increasing IgG4 responses with specificity for VSA of isolates from children with severe malaria. These findings imply that the predictive value of prospectively measured cross-reactive VSA-specific IgG antibodies with respect to protection against malaria in African children depends both on their isotype and on their fine specificity.
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PMID:Immunoglobulin G isotype responses to erythrocyte surface-expressed variant antigens of Plasmodium falciparum predict protection from malaria in African children. 1578 72

The sickle cell trait (HbAS) protects against severe Plasmodium falciparum malaria in young African children. We investigated the extent of the association between HbAS and antibodies directed to parasite-derived variant surface antigens (VSAs) on the membrane of infected erythrocytes. We measured immunoglobulin G (IgG) responses with specificity for VSAs of 2 heterologous parasite isolates in 458 Gabonese children aged between 6 months and 11 years. Logistic regression analyses showed a highly significant independent association (P<.001) between carriage of HbAS and the presence of IgG anti-VSA responses; this association was related specifically to IgG1 and IgG4 subclasses in the anti-VSA profile. IgG2 and IgG3 anti-VSA responses were both independently associated with older age, consistent with the pattern observed in semi-immune adults. The results imply that enhanced levels of cross-reactive anti-VSA responses in children with HbAS may be intimately associated with the protection they have against malaria.
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PMID:The sickle cell trait is associated with enhanced immunoglobulin G antibody responses to Plasmodium falciparum variant surface antigens. 1583 89

The well-established relative resistance to malaria observed in the Fulani as compared with other sympatric tribes in West Africa has been attributed to their higher levels of serum immunoglobulin (Ig) G antibodies to malarial antigens. In this study, we confirm and extend the previous findings by analyses of the levels of IgM, IgG and IgG subclasses of anti-malarial antibodies in asymptomatic individuals of different sympatric tribes in Burkina Faso (Fulani/Mossi) and Mali (Fulani/Dogon). The Fulani showed significantly higher median concentrations of anti-malarial IgG and IgM antibodies than the sympatric tribes at both locations. Although the overall subclass pattern of antibodies did not differ between the tribes, with IgG1 and IgG3 as dominant, the Fulani showed consistently significantly higher levels of these subclasses as compared with those of the non-Fulani individuals. No significant differences were seen in the levels of total IgG between the tribes, but the Fulani showed significantly higher levels of total IgM than their neighbours in both countries. While the antibody levels to some nonmalarial antigens showed the same pattern of differences seen for antibody levels to malaria antigens, no significant such differences were seen with antibodies to other nonmalarial antigens. In conclusion, our results show that the Fulani in two different countries show higher levels of anti-malarial antibodies than sympatric tribes, and this appears not to be a reflection of a general hyper-reactivity in the Fulani.
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PMID:Distinct interethnic differences in immunoglobulin G class/subclass and immunoglobulin M antibody responses to malaria antigens but not in immunoglobulin G responses to nonmalarial antigens in sympatric tribes living in West Africa. 1585 23


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