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

There are several mechanisms responsible for the extensive antigenic diversity found in the asexual blood stages of Plasmodium falciparum. Failure to express antigens is a feature of many isolates cultured in vitro but probably is not a major cause of antigenic diversity in vivo. Numerous point mutations occur in allelic forms of asexual blood stage antigens and are assumed to contribute to antigenic diversity but as yet few such mutations have been mapped to antigenic epitopes. A major cause of antigenic diversity is the expression of different repetitive sequences in allelic forms of several antigens including the S-antigen and the two merozoite surface antigens, MSA-1 and MSA-2. The sequencing data indicates that S-antigen genes fall into many allelic families whereas both MSA-1 and MSA-2 are dimorphic. Further diversity has arisen as a result of intragenic recombinations between the dimorphic forms of both MSA-1 and MSA-2. In addition to this diversity reflecting the expression of different allelic genes, asexual blood stages of malaria parasites undergo antigenic variation in that clonal parasite populations can vary the form of an antigen on the surface of infected erythrocytes. Antibodies or DNA probes directed against variable repeat sequences can be used to distinguish different isolates of P. falciparum. The use of antibodies to S-antigen repeats has been particularly useful for typing the parasites causing infections. The application of S-antigen typing to field studies in Papua New Guinea has demonstrated marked diversity in the parasites causing infections in one area.
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PMID:Antigenic diversity in Plasmodium falciparum. 182 Jul 15

The rotavirus glycoprotein VP7 has a cleavable signal peptide and is normally resident as an integral membrane protein in the ER of infected cells. A gene was constructed in which the VP7 H2 signal peptide was replaced by one from influenza hemagglutinin. COS cells transfected with this gene produced VP7 with the correct amino terminus, but the protein was rapidly secreted. Uncleaved VP7 from either precursor was not detected in cells after brief pulse-labeling, suggesting that the signal peptide was not acting as a temporary anchor; rather, it exerted its effect despite rapid cleavage. By splicing the H2 signal peptide onto another reporter protein, the malaria S-antigen, we demonstrated that H2 was necessary, but not itself sufficient, for targeting and retention. We propose that an interaction between the cleaved signal peptide and other downstream sequences in VP7 is required for retention of this protein in the ER as an integral membrane polypeptide.
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PMID:The signal peptide of the rotavirus glycoprotein VP7 is essential for its retention in the ER as an integral membrane protein. 253 41

Cross-sectional and longitudinal village-based studies of the transmission dynamics of an S-antigen serotype of the asexual erythrocyte stages of Plasmodium falciparum have been carried out in Madang, Papua New Guinea (PNG). Sera collected from village residents were screened for circulating S-antigen of the FC27 serotype by enzyme-linked immunosorbent assay (ELISA). The prevalence of the FC27 S-antigen was found to vary between villages at a given point in time, as well as within a village over time. Residents of villages 2-5 km apart were infected with P. falciparum of different S-antigen serotypes. This study documents the periodic nature of transmission of a sub-population of P. falciparum defined by the FC27 S-antigen. The variation in a small area in the prevalence of this serotype of P. falciparum in Madang illustrates the complexities of malaria transmission which must be considered in the design of malaria vaccine trials.
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PMID:Small area variation in prevalence of an S-antigen serotype of Plasmodium falciparum in villages of Madang, Papua New Guinea. 265 60

Considerable antigenic heterogeneity of Plasmodium falciparum has been demonstrated in natural parasite populations. However, very little is known about the relative virulence, transmission efficiency and prevalence over space and time of parasites expressing different serotypes of variant antigens. The recent application of recombinant DNA techniques to express a wide range of P. falciparum antigens in Escherichia coli has led to a better understanding of the molecular basis of antigenic diversity of a number of parasite proteins including the precursor to the major merozoite surface antigen (PMMSA) and the heat-stable S-antigens. Highly specific reagents such as DNA probes, monoclonal antibodies and polyclonal antisera to either cloned antigens or synthetic peptides have become available for serotypic analysis of natural parasite populations. With these reagents important epidemiological questions can now be asked concerning the population biology of different serotypes of P. falciparum. The use of the polymorphic S-antigen system as a serotypic marker to analyse the transmission dynamics of P. falciparum in Madang, Papua New Guinea (PNG) is discussed. Results of serotyping studies with the S-antigen system highlight the complexities of malaria transmission, which require consideration in the design of malaria vaccine trials.
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PMID:New approaches to the serotypic analysis of the epidemiology of Plasmodium falciparum. 290 54

We describe a procedure that uses polyspecific human sera for screening Escherichia coli colonies expressing cloned Plasmodium falciparum cDNA sequences in order to detect colonies that react differentially with different sera. This procedure can be used for two distinct purposes. First, it enables the isolation of clones encoding specified antigenic sequences present in the complex mixture, without purification of either antigens or antibodies by conventional procedures. This requires that the antigen can be expressed in E. coli and that antisera are available that differ substantially in their reactivities to the component of interest. To develop the procedure, we used two polyspecific sera that shared many anti-P. falciparum specificities but differed in that only one was reactive to the isolate-specific S antigen of P. falciparum strain FCQ27/PNG (called FC27). Differential screening with the two sera identified 30 cDNA clones, and colony hybridization confirmed that 25 of these express S-antigen sequences. Second, the procedure identifies defined antibody specificities within polyspecific human sera by virtue of their ability to react with any given cDNA clone. The procedure has been used here to identify antibody specificities that increase dramatically in titer between the acute and convalescent phases of malaria in certain individuals and, hence, to isolate clones encoding the corresponding antigens.
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PMID:Differential antibody screening of cloned Plasmodium falciparum sequences expressed in Escherichia coli: procedure for isolation of defined antigens and analysis of human antisera. 637 14

Numerous polymorphic antigens of the asexual erythrocytic stages of P. falciparum are now well characterized. Diversity in some of these antigens, including MSA-1, MSA-2 and the S-antigen is associated with changes in the repeat sequences which are frequently a prominent structural feature of malaria antigens. It is not known whether the variation in repeats causes allelic gene products to adopt different conformations but variation in and around the repeats in SPAM, a newly characterized secreted antigen, preserve the unusual alanine-heptad repeats which we assume generate a helical bundle in this protein. Mutations in non-repetitive regions of the S-antigen and in AMA-1, an antigen lacking repeats, are strongly biased towards those which alter the amino acid sequence. This and other evidence indicates the operation of biological selection but the role of immune responses as a selection pressure operating on these diverse antigens remains to be established.
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PMID:Molecular variation in Plasmodium falciparum: polymorphic antigens of asexual erythrocytic stages. 810 Jun 73

A mixture of Plasmodium falciparum exoantigens inducing lymphocyte activation and cytokine production was shown to contain the malaria vaccine candidate, the serine-stretch protein. This protein was shown serologically to correspond to Ag2, an exoantigen recognized by antibodies linked with protection against malaria. The glycophorin-binding protein, the histidine-rich protein II, the S-antigen, the heat shock protein 70, the ring-infected erythrocyte surface antigen, and the apical membrane antigen-1 were also shown serologically to be present in the mixture of exoantigens.
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PMID:Serine-stretch protein (SERP) of Plasmodium falciparum corresponds to the exoantigen Ag2, a target of antibodies associated with protection against malaria. 816 1

We describe Plasmodium falciparum genetic diversity in coastal Kenya, typing S-antigen and the merozoite surface proteins 1 and 2 (MSP-1 and MSP-2) in field isolates by the polymerase chain reaction (PCR). Malaria in coastal Kenya is characterized by low seasonal transmission, and a relatively high incidence of severe disease, which tends to occur in time-space clusters. We chose the highly polymorphic S-antigen as a marker for localized parasite diversity because it has been shown to vary in serotype prevalence in time and space. A total of 261 children (up to nine years of age) in two neighboring locations with different transmission rates were sampled for blood-stage parasites in cross-sectional surveys before and after the main transmission period in 1991, and also in a concomitant one-year longitudinal survey tracing clinical infections. Six major sequence types of S-antigen were identified, which were subdivided into 70 alleles; however, only 50% of isolates were typeable. The S-antigen sequence types varied qualitatively between locations, over time, and between asymptomatic and clinical disease infections, but not between different age groups. The MSP-1 and MSP-2 sequence type prevalences, in contrast, did not differ in any of these comparisons. We describe the use of the Mantel test for assessing clustering of individual parasite alleles at the household level, and demonstrate low-level clustering of MSP-1 and MSP-2 alleles and S-antigen sequence types, at the end of a long period of low transmission.
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PMID:Limited spatial clustering of individual Plasmodium falciparum alleles in field isolates from coastal Kenya. 928 18

The malaria genome encodes over 5,000 proteins and many of these have also been proposed to be potential vaccine candidates, although few of these have been tested clinically. RH5 is one of the leading blood-stage Plasmodium falciparum malaria vaccine antigens and Phase I/II clinical trials of vaccines containing this antigen are currently underway. Its likely mechanism of action is to elicit antibodies that can neutralize merozoites by blocking their invasion of red blood cells (RBC). However, many other antigens could also elicit neutralizing antibodies against the merozoite, and most of these have never been compared directly to RH5. The objective of this study was to compare a range of blood-stage antigens to RH5, to identify any antigens that outperform or synergize with anti-RH5 antibodies. We selected 55 gene products, covering 15 candidate antigens that have been described in the literature and 40 genes selected on the basis of bioinformatics functional prediction. We were able to make 20 protein-in-adjuvant vaccines from the original selection. Of these, S-antigen and CyRPA robustly elicited antibodies with neutralizing properties. Anti-CyRPA IgG generally showed additive GIA with anti-RH5 IgG, although high levels of anti-CyRPA-specific rabbit polyclonal IgG were required to achieve 50% GIA. Our data suggest that further vaccine antigen screening efforts are required to identify a second merozoite target with similar antibody-susceptibility to RH5.
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PMID:Functional Comparison of Blood-Stage Plasmodium falciparum Malaria Vaccine Candidate Antigens. 3121 95