Different Regions of the Malaria Merozoite Surface Protein 1 of<i>Plasmodium chabaudi</i>Elicit Distinct T-Cell and Antibody Isotype Responses

Quin, Stuart; Langhorne, Jean

doi:10.1128/iai.69.4.2245-2251.2001

Cited by 32 publications

(48 citation statements)

References 48 publications

(48 reference statements)

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“…l TDM-MPL adjuvant; RIBI, Sigma) or adjuvant alone, was administered intraperitoneally at 2-3-week intervals. Mice were injected intravenously with 10 3 P. chabaudi chabaudi (AS) infected erythrocytes, and the course of infection monitored as described previously [25].…”

Section: Mice Parasites and Immunization Schedulementioning

confidence: 99%

“…Antigen-specific IgG1 and IgG2a antibodies were measured by ELISA as described previously [25]. Positive (hyperimmune plasma or serum for P. chabaudi and P. yoelii, respectively) and negative (normal BALB/c mouse plasma, NMP) control series were included on each plate.…”

Section: Measurement Of Msp1 19 Specific Antibodymentioning

confidence: 99%

“…We have previously suggested that the relatively poor immunogenicity of this part of MSP1 is caused by its structural complexity, as it was only available for loading onto recycling MHC class II molecules after reduction of its disulfides [24]. In both human and rodent malaria, T cell responses are biased towards parts of MSP1 N-terminal to MSP1 19 [24][25][26]. Here we investigate the ability of asparagine endopeptidase (AEP) [27], one of the major lysosomal proteases responsible for antigen processing, to digest MSP1 19 from two different rodent malaria parasites and determine whether removal of disulfide bonds by reduction and alkylation allows faster processing and faster antibody response in vivo.…”

Section: Introductionmentioning

confidence: 99%

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Disulfide bonds in merozoite surface protein 1 of the malaria parasite impede efficient antigen processing and affect the in vivo antibody response

Hensmann

Moss

et al. 2004

Eur J Immunol

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The 19 kDa C‐terminal fragment of the malaria parasite merozoite surface protein 1 (MSP119) is a leading malaria vaccine candidate. In rodents, high antibody levels to this protein confer protective immunity, and can be generated by immunization with the antigen in adjuvants. In natural human infections, however, MSP119‐specific antibody responses can be short‐lived andcomparatively low, despite repeated exposure to infection. The tightly folded structure of MSP119 is stabilized by five or six disulfide bonds. These bonds impede antigen processing and, thereby, may affect the generation of CD4+ T cells providing help for B cells. Asparagine endopeptidase could digest unfolded, but not native MSP119 in vitro. Immunization with unfolded MSP119 resulted in a faster antibody response, and a combination of unfolded and native MSP119 increased antibody responses to the native form. Immunization with either form of the antigen activated similar numbers of CD4+ T cells, but, unlike the antibody response, CD4+ T cells immunized with one form of MSP119 were able to respond in vitro to the other form of the protein. Although the reduced form of MSP119 does not induce protective antibodies, our data suggest that inclusion of unfolded protein may improve the efficacy of MSP119 as a vaccine.See correction http://dx.doi.org/10.1002/eji.200490004

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Section: Mice Parasites and Immunization Schedulementioning

confidence: 99%

Section: Measurement Of Msp1 19 Specific Antibodymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Disulfide bonds in merozoite surface protein 1 of the malaria parasite impede efficient antigen processing and affect the in vivo antibody response

Hensmann

Moss

et al. 2004

Eur J Immunol

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“…Results are expressed as arbitrary units (AU) of specific antibody based on a standard hyperimmune plasma (1000 AU). 15 Results are plotted as geometric means, with SEM of 7 animals at each point. Statistics were performed in Prism (GraphPad) using the Student t test, with P equal to .05 considered significant.…”

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confidence: 99%

Malaria-specific transgenic CD4+ T cells protect immunodeficient mice from lethal infection and demonstrate requirement for a protective threshold of antibody production for parasite clearance

Stephens

Albano

Quin

et al. 2005

Blood

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T cells are important in the immune response to malaria, both for their cytokines and their help for antibody production. To look at the relative importance of these roles, a T-cell receptor (TCR) transgenic mouse has been generated carrying a TCR specific for an epitope of the merozoite surface protein 1 (MSP-1) of the malaria parasite, Plasmodium chabaudi. In adoptive transfer experiments, malaria-specific CD4 ؉ T cells expand and produce interferon ␥ (IFN-␥) early in infection, but the population contracts quickly despite prolonged persistence of the parasite. MSP-1-specific CD4 ؉ cells can protect immunodeficient mice from lethal infection; however, the parasite is only completely cleared in the presence of B cells showing that T helper cells are critical. Levels of malariaspecific antibody and the speed of their production clearly correlate with the time of resolution of infection, indicating that a critical threshold of antibody production is required for parasite clearance. Furthermore, T cells specific for a shed portion of MSP-1 are able to provide help for antibody to the protective region, which remains bound to the infected erythrocyte, suggesting that MSP-1 has all of the components necessary for a good vaccine. IntroductionT helper cells are essential for a protective immune response to the blood stages of the rodent malaria parasite, Plasmodium chabaudi chabaudi (AS). 1 There is debate, however, over the extent to which T cells protect via Th1 cytokine-mediated mechanisms or by the antibodies that they help to produce. Both mechanisms dominate the T-cell response to P chabaudi in turn, with an early Th1-type cytokine response, which switches later in infection to one that provides effective help for malaria-specific antibody production and produces less interferon ␥ (IFN-␥). 2,3 Increased T-helper cell activity in the later stages 3 is clearly beneficial because experiments in B cell-deficient mice demonstrate that B cells and antibodies are required for complete clearance of parasites, 4-6 although the requirements and specificity of T-cell help and antibody for rapid clearance or immunity to reinfection are not known.To determine the precise role of malaria-specific T helper cells and the potential of an important vaccine antigen, merozoite surface protein 1 (MSP-1), in the protection from and clearance of malaria infection, we have generated a T-cell receptor (TCR) transgenic mouse with a TCR specific for P chabaudi MSP-1. This molecule is expressed on the invasive merozoite surface, 7 and its C-terminal domain can induce a protective immune response. [8][9][10][11] However, this domain is not efficiently processed by antigenpresenting cells and is a less effective inducer of CD4 ϩ T-cell responses than other parts of MSP-1. 10,12,13 For more effective vaccination strategies it would be important to know whether CD4 ϩ T-cell help can be generated from other parts of MSP-1, which are more readily processed and presented on antigenpresenting cells. The MSP-1-specific TCR of our transgenic mouse,...

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“…The soluble MSP-1 33 , corresponding to the N-terminal region of MSP-1 42 , sheds from the surface, 19,20 whereas the membranebound MSP-1 19 remains anchored to the merozoite and is carried into the new erythrocyte. 21 MSP-1 42 is one of the leading candidates for blood-stage malaria vaccines because it is able to induce cell-mediated and humoral immune responses, 22 and its proteolytic product MSP-1 33 is responsible for the cellular immune protection. 23 For example, P. yoelii MSP-1 33 induces effector T cells that could assist in protective B cells response and mediate significant antiparasitic activity against P. yoelii.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Recombinant Plasmodium knowlesi Merozoite Surface Protein-133 for Detection of Human Malaria

Cheong

Lau

Fong

et al. 2013

The American Society of Tropical Medicine and Hygiene

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Abstract. Plasmodium knowlesi is now known as the fifth Plasmodium species that can cause human malaria. The Plasmodium merozoite surface protein (MSP) has been reported to be potential target for vaccination and diagnosis of malaria. MSP-1 33 has been shown to be immunogenic and its T cell epitopes could mediate cellular immune protection. However, limited studies have focused on P. knowlesi MSP-1 33 . In this study, an approximately 28-kDa recombinant P. knowlesi MSP-1 33 (pkMSP-1 33 ) was expressed by using an Escherichia coli system. The purified pkMSP-1 33 reacted with serum samples of patients infected with P. knowlesi (31 of 31, 100%) and non-P. knowlesi malaria (27 of 28, 96.43%) by Western blotting. The pkMSP-1 33 also reacted with P. knowlesi (25 of 31, 80.65%) and non-P. knowlesi malaria sera (20 of 28, 71.43%) in an enzyme-linked immunosorbent assay (ELISA). Most of the non-malarial infection (49 of 52 in by Western blotting and 46 of 52 in the ELISA) and healthy donor serum samples (65 of 65 by Western blotting and ELISA) did not react with recombinant pkMSP-1 33 .

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Different Regions of the Malaria Merozoite Surface Protein 1 ofPlasmodium chabaudiElicit Distinct T-Cell and Antibody Isotype Responses

Cited by 32 publications

References 48 publications

Disulfide bonds in merozoite surface protein 1 of the malaria parasite impede efficient antigen processing and affect the in vivo antibody response

Disulfide bonds in merozoite surface protein 1 of the malaria parasite impede efficient antigen processing and affect the in vivo antibody response

Malaria-specific transgenic CD4+ T cells protect immunodeficient mice from lethal infection and demonstrate requirement for a protective threshold of antibody production for parasite clearance

Evaluation of Recombinant Plasmodium knowlesi Merozoite Surface Protein-133 for Detection of Human Malaria

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