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

The ability of deproteinated malaria exoantigens from Plasmodium falciparum (Pf-MT) and P. berghei ANKA (PbA-MT) to activate murine haematopoietic cells was analysed in vitro. Malaria toxins (MT) of both plasmodium species induced cell proliferation and the production of IFN-gamma in overnight and long-term (5 days) spleen and bone marrow cultures and a reduction of the number of TNF-alpha spot forming cells (SFC). When added to cells of malaria-experienced animals, MT decreased the number of IL-4 SPC and increased the number of IL-5 SPC. However, the same proliferative and IFN-gamma induction properties as in naive cells were observed. Simultaneous addition of IL-2 and PbA-MT to spleen cells inhibited the proliferation but increased the IFN-gamma production usually induced by IL-2. Flow cytometric analysis revealed that the addition of MT triggered an expansion of CD3+ and GR1+ cell populations. Our results suggest that malaria toxins of different species can induce an immediate and strong proliferation and a TH1-type cytokine release by murine cells, independently of previous in vivo priming.
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PMID:Malaria toxins: effects on murine spleen and bone marrow cell proliferation and cytokine production in vitro. 936 98

Liver-stage antigen 1 (LSA1) is one of several pre-erythrocytic antigens considered for inclusion in a multiantigen, multistage subunit vaccine against falciparum malaria. We examined T-cell proliferation and cytokine responses to peptides corresponding to amino acids 84 to 107, 1813 to 1835, and 1888 to 1909 of LSA1 in asymptomatic adults living in an area of Papua New Guinea where malaria is holoendemic. Whereas T cells from North Americans never exposed to malaria did not respond to any of the peptides, those from 52 of 55 adults from the area where malaria is endemic had vigorous proliferation responses to one or more of the LSA1 peptides (mean stimulation indices of 6.8 to 7.2). Gamma interferon (IFN-gamma) production driven by LSA1 peptides ranged from 34 to more than 3,500 pg/2 x 10(6) cells, was derived primarily from CD8+ cells, and was dissociated from T-cell proliferation. The frequencies of IFN-gamma response to the amino acid 1819 to 1835 and 1888 to 1909 peptides were significantly greater than that to the amino acid 84 to 107 peptide (87 and 88% versus 33% of subjects; P < 0.0001). In contrast to proliferation and IFN-gamma, interleukin 4 (IL-4) and/or IL-5 responses to LSA1 peptides were detected in only 18% of the subjects. These data show that T-cell immunity to epitopes in the N- and C-terminal regions of LSA1 are common in persons living in this area of Papua New Guinea where malaria is endemic. The dominance of type 1 CD8 cell IFN-gamma responses is consistent with a role for this T-cell population in immunity to liver-stage Plasmodium falciparum in humans.
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PMID:T-cell immunity to peptide epitopes of liver-stage antigen 1 in an area of Papua New Guinea in which malaria is holoendemic. 939 99

The functional properties, regarding parasite growth inhibition in vitro, the cytotoxic potential and cytokine profiles of human gammadelta+ and alphabeta+ T cells, T-cell lines and clones stimulated with Plasmodium falciparum-antigen-or T-cell mitogen in vitro were investigated. Using reverse transcriptase-polymerase chain reaction (RT-PCR) and specific primers, mRNA for the cytolytic molecules perforin, granzyme A and B, Fas and Fas ligand (FasL) were detected in both the gammadelta- and the alphabetaT cells. Despite this fact, only gammadeltaT cells inhibited, both Vdelta1+ and Vdelta2+, the in vitro growth of the asexual blood stages in a dose dependent manner. The inhibition required cell-to-cell contact and was not observed until the second parasite replication implied that the likely gammadeltaT-cell target was the extracellular merozoite or schizont. The failure of alphabetaT cells to inhibit the growth of the parasite suggests requirement of additional cytolytic molecules/signals or different receptor specificities exhibited by the gammadeltaT cells. Both the gammadelta- and alphabetaT cells expressed mRNA for a large number of cytokines. Interferon (IFN)-gamma, interleukin (IL) IL-5, IL-6, IL-8, tumour necrosis factor alpha (TNFalpha), tumour necrosis factor beta (TNF-beta)/lymphotoxin (LT) and T-cell growth factor beta-1 (TGF-beta1) were observed in all activated clones tested. No IL-3 was detected, while IL-1beta, IL-2, IL-4, IL-10 and GM-CSF were variably expressed. In conclusion, our data show that gammadeltaT cells in malaria nonimmune individuals inhibit the asexual blood stages of P. falciparum malaria, while similarly activated alphabetaT cells do not. Thus, it is likely that the gammadeltaT cells could play a mandatory role in the elimination of parasites and/or the regulation of the early immune response to malaria infection.
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PMID:Human gamma delta T cells that inhibit the in vitro growth of the asexual blood stages of the Plasmodium falciparum parasite express cytolytic and proinflammatory molecules. 1060 13

Seasonal epidemics of malaria occur in highland areas of western Kenya where transmission intensity varies according to rainfall. This study describes the seasonal changes in cytokine responses to Plasmodium falciparum liver-stage antigen 1 (LSA-1) by children (< or =17 years old) and adults (> or =18 years old) living in such a highland area. Fourteen- to 24-mer peptides corresponding to the N- and C-terminal nonrepeat regions of LSA-1 stimulated production of interleukin-5 (IL-5), interleukin-10 (IL-10), gamma interferon (IFN-gamma), and tumor necrosis factor alpha (TNF-alpha) by peripheral blood mononuclear cells (PBMC) from 17 to 73% of individuals in both age groups in both seasons. IL-10 and TNF-alpha responses were more frequent during the high-transmission, rainy season than during the low-transmission, dry season (73 and 67% versus 17 and 25% response rates, respectively). In contrast, there was no seasonal change in the proportion of LSA-1-driven IFN-gamma and IL-5 responses. Children produced less IFN-gamma than adults, but IL-5, IL-10, and TNF-alpha levels were similar for both age groups. Depletion of CD8(+) cells from PBMC decreased IFN-gamma but increased IL-10 production. Individuals with LSA-1-stimulated IL-10 responses in the dry season were less likely to become reinfected in the subsequent rainy season than those without IL-10 responses (25% versus 49%; P = 0.083). These data support the notion that maintenance of LSA-1-driven IL-10 and TNF-alpha responses requires repeated and sustained exposure to liver-stage P. falciparum. In contrast, IFN-gamma responses increase slowly with age but persist once acquired. CD8(+) T cells are the major source of IFN-gamma but may suppress production or secretion of IL-10.
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PMID:Cytokine responses to Plasmodium falciparum liver-stage antigen 1 vary in rainy and dry seasons in highland Kenya. 1094 44

Vaccines that induce mosquito-killing (mosquitocidal) activity could substantially reduce the transmission of certain mosquito-borne diseases, especially vaccines against African malaria vectors, such as the mosquito Anopheles gambiae. To generate and characterize antimosquito immunity we immunized groups of mice with two individual A. gambiae midgut cDNAs, Ag-Aper1 (a secreted peritrophic matrix protein) and AgMuc1 (a midgut-bound mucin), and an A. gambiae midgut cDNA library from blood-fed mosquitoes. We observed significantly increased mortality among mosquitoes that fed on either the AgMuc1- or the cDNA library-immunized mice compared to that of controls, but no differences were observed among those fed on Ag-Aper1-immunized mice. Analysis of the humoral and cellular immune responses from mice showed that the induced mosquitocidal effect was associated with immune profiles characterized by elevated tumor necrosis factor alpha and gamma interferon cytokine levels and very low antibody titers. Furthermore, an additional immunization of cDNA library-immunized mice with midgut protein shifted immunity toward a Th2-type immune response, characterized by elevated antibody titers and high interleukin-5 and interleukin-10 cytokine levels; importantly, mosquitoes feeding on these mice exhibited no undue mortality. Finally, when immune sera was ingested by mosquitoes through a membrane feeder, no effect on mosquito mortality was observed, indicating that serum factors alone were not responsible for the mosquitocidal effect. Our results demonstrate that mosquitocidal immunity in mice can be consistently generated by midgut cDNA immunization and suggest this cDNA-induced mosquitocidal immunity is cell mediated.
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PMID:Induction of mosquitocidal activity in mice immunized with Anopheles gambiae midgut cDNA. 1265 23

Passage of parasites and their antigens across the placenta occurs with metazoan as well as protozoan parasites, and this study addressed to which extent exposure to and infection of mothers with Plasmodium spp. and Entamoeba histolytica/dispar has sensitized their offspring for parasite-specific immune responses. While at delivery none of the mothers presented with an acute malaria attack, 42% were seropositive for P. falciparum. In half of the mothers cysts of E. histolytica/dispar were detected in stool specimen, 51% of them were found seropositive for E. histolytica, and E. histolytica-specific immunoglobulin A (IgA) responses were detected in neonates of seropositive mothers as well. Umbilical cord blood cells (UCBC) from neonates, when activated with the mitogen phytohaemagglutinine (PHA) and bacterial streptolysin O (SL-O), released significantly less interferon (IFN)-gamma, interleukin (IL)-10 and tumor necrosis factor (TNF)-alpha into cell culture supernatants than peripheral blood cells (PBMC) of mothers. In response to Plasmodium- and Entamoeba-specific antigens UCBC and PBMC produced equal amounts of IL-1beta, TNF-alpha, IFN-gamma and IL-5, but PBMC from mothers secreted significantly more IL-10. Parasite-specific production of inflammatory and Th(1)- and Th(2)-type cytokines was similar in newborns of Plasmodium and Entamoeba seropositive and seronegative mothers. In summary, repeated exposure and subclinical infection of mothers with E. histolytica or P. falciparum will suffice to prime in utero their children for inflammatory and both Th(1)- and Th(2)-type cytokine responses, and such broad and mixed cytokine spectrum may be of advantage upon secondary parasite challenge in later life.
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PMID:Parasite-specific antibody and cytokine profiles in newborns from Plasmodium falciparum and Entamoeba histolytica/dispar-infected mothers. 1505 89

Merozoite surface protein-9 of Plasmodium vivax (PvMSP-9) is highly conserved and present in several malaria species. Here, we present the immunogenic properties of two recombinant glutathione S-transferase (GST) fusion proteins comprising the N-terminus (PvMSP-9-Nt) and the second block of tandem repeats (PvMSP-9-RepII) of PvMSP9. These recombinants proteins were used to immunize BALB/c mice. The specificity and subtyping of the antibodies and the cellular immune responses were evaluated by enzyme-linked immunosorbent assay (ELISA) and ELISPOT, respectively, using the recombinant proteins as antigens. Our results demonstrate that both the N-terminal and the tandem repeat regions of MSP9 are immunogenic in mice. The ELISA antibody titers elicited by PvMSP-9-Nt were significantly higher (1:819,200) than the antibody titers elicited by PvMSP-9-RII (1:409,600). Analysis of IgG subclasses showed that both recombinant proteins induce similar antibody patterns where IgG1, IgG2a and IgG2b were most predominant. Moreover, all sera from mice immunized with either PvMSP-9-Nt or PvMSP-9-RII, which were positive by ELISA showed reactivity with P. vivax, P. cynomolgi, P. knowlesi and P. coatneyi schizonts by immunofluorescence assays (IFA). Similar results were observed in western immunoblot analyses using parasite extracts. Furthermore, immunization of mice with the PvMSP-9-Nt upon stimulation with PvMSP-9-Nt secreted IFN-gamma and IL-5. We have also used the two PvMSP-9 recombinant constructs to show that individuals exposed to P. vivax infections in an endemic area of Brazil had IgG antibodies reactive with the recombinant proteins.
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PMID:Immunogenicity of Plasmodium vivax merozoite surface protein-9 recombinant proteins expressed in E. coli. 1512 16

Malaria vaccine RTS,S combined with thrombospondin-related anonymous protein (TRAP) and formulated with AS02A (RTS,S+TRAP/AS02A) is safe and immunogenic in adult humans and rhesus monkeys (Macaca mulatta). Here, RTS,S+TRAP/AS02A was administered on a 0-, 1-, and 3-month schedule to three cohorts of infant monkeys, along with adult comparators. Cohort 1 evaluated 1/5, 1/2, and full adult doses, with the first dose administration at one month of age; cohort 2 monkeys received full adult doses, with the first dose administration at one versus three months of age; and, cohort 3 compared infants gestated in mothers with or without previous RTS,S/AS02A immunization. Immunization site reactogenicity was mild. Some infants, including the phosphate-buffered saline only recipient, developed transient iron-deficiency anemia, which is considered a result of repeated phlebotomies. All RTS,S+TRAP/AS02A regimens induced vigorous antibody responses that persisted through 12 weeks after the last vaccine dose. Modest lymphoproliferative and ELISPOT (interferon-gamma and interleukin-5) responses, particularly to TRAP, approximated adult comparators. RTS,S+TRAP/AS02A was safe and well tolerated. Vigorous antibody production and modest, selective cell-mediated immune responses suggest that RTS,S+TRAP/AS02A may be immunogenic in human infants.
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PMID:Safety and immunogenicity of rts,s+trap malaria vaccine, formulated in the as02a adjuvant system, in infant rhesus monkeys. 1515 81

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

Prenatal immunity to Plasmodium falciparum merozoite proteins involved in erythrocyte invasion may contribute to the partial protection against malaria that is acquired during infancy in areas of stable malaria transmission. We examined newborn and maternal cytokine and antibody responses to merozoite surface protein-1 (MSP-1), ribosomal phosphoprotein P0 (PfP0), and region II of erythrocyte binding antigen-175 (EBA-175) in infant-mother pairs in Kenya. Overall, 82 of 167 (50%), 106 of 176 (60%), and 38 of 84 (45%) cord blood lymphocytes (CBL) from newborns produced one or more cytokines in response to MSP-1, PfP0, and EBA-175, respectively. Newborns of primigravid and/or malaria-infected women were more likely to have antigen-responsive CBL than were newborns of multigravid and/or uninfected women at delivery. Newborn cytokine responses did not match those of their mothers and fell into three distinct categories, Th1 (21 of 55 CBL donors produced only gamma interferon and/or interleukin 2 [IL-2]), Th2 (21 of 55 produced only IL-5 and/or IL-13), and mixed Th1/Th2 (13 of 55). Newborns produced more IL-10 than adults. High and low levels of cord blood IL-12 p70 production induced by anti-CD40 activation were associated with malaria-specific Th1 and Th2 responses, respectively. Antigen-responsive CBL in some newborns were detected only after depletion of IL-10-secreting CD8 cells with enrichment for CD4 cells. These data indicate that prenatal sensitization to blood-stage Plasmodium falciparum occurs frequently in areas where malaria is holoendemic. Modulation of this immunity, possibly by maternal parity and malaria, may affect the acquisition of protective immunity against malaria during infancy.
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PMID:Distinct Th1- and Th2-Type prenatal cytokine responses to Plasmodium falciparum erythrocyte invasion ligands. 1590 75


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