Expression of the Precursor of the Major Merozoite Surface Antigens During the Hepatic Stage of Malaria

Suhrbier, Andreas; Holder, Anthony A.; Wiser, Mark F.; Nicholas, J.; Sinden, Robert E.

doi:10.4269/ajtmh.1989.40.351

Cited by 31 publications

(20 citation statements)

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“…MSP1 is expressed not only at the blood stage but also in EE forms of malaria parasites (19,20). In this study we confirmed the expression of MSP1 in the liver by RT-PCR and investigated whether this antigen could be a target of protective immunity against liver-stage parasites by an immunization protocol that used MSP1-hsc70 fusion protein.…”

Section: Discussionmentioning

confidence: 60%

“…MSP1 is a leading candidate antigen for a malaria vaccine at the blood stage, but its expression is also reported in the EE forms of malaria infection (19,20). To confirm the expression of MSP1 during the liver stage, we performed RT-PCR of liver RNA 0 to 4 days after sporozoite infection (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…One of them is merozoite surface protein 1 (MSP1), a prominent candidate antigen for a bloodstage malaria vaccine. Using monoclonal antibodies specific for MSP1, the precursors and proteolytic products of MSP1 were shown to be expressed in the EE stage (19,20). MSP1 is synthesized as a precursor of 180 to 250 kDa and is bound to the merozoite plasma membrane via a C-terminal glycosylphosphatidylinositol moiety (9).…”

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confidence: 99%

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Merozoite Surface Protein 1-Specific Immune Response Is Protective against Exoerythrocytic Forms ofPlasmodium yoelii

et al. 2002

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One of the difficulties in developing an effective malaria vaccine is the antigenic change of the parasite during the life cycle. It is desirable that vaccine-induced protective immunity be effective at different stages of parasite development. Merozoite surface protein 1 (MSP1) is a candidate vaccine antigen against blood-stage malaria, but it is also expressed in the exoerythrocytic forms. It was not known, however, whether the anti-MSP1 immune response is effective against the liver-stage malaria parasite. We generated a recombinant protein of MSP1 fused to heat-shock cognate protein 70 (hsc70) and studied its vaccination effect. When C57BL/6 mice were immunized with the fusion protein prior to challenge infection with Plasmodium yoelii sporozoites, the onset of parasitemia was delayed or no parasitemia was observed. To determine whether this was due to the protective immunity against liver-stage parasites, P. yoelii-specific rRNA in the infected liver was quantitated by real-time reverse transcription-PCR analysis. The level of parasite-specific rRNA was reduced in mice immunized with the fusion protein of MSP1 and hsc70 but not with hsc70 alone, indicating that MSP1-specific immunity can be protective against the exoerythrocytic form of the parasite. Furthermore, the adoptive transfer experiments of immune lymphocytes and serum into naive mice suggested that the protective immunity was dependent on cellular and not humoral immunity. Finally, the vaccine-induced protection was also observed in A/J, C3H, and BALB/c mice, suggesting that MSP1-specific protective immunity at the exoerythrocytic stage can be induced in animals over a wide range of genetic backgrounds.

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Section: Discussionmentioning

confidence: 60%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

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Merozoite Surface Protein 1-Specific Immune Response Is Protective against Exoerythrocytic Forms ofPlasmodium yoelii

et al. 2002

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“…There is evidence that MSP1 is expressed in hepatocytes of the liver stage (2,46,47). Although protective humoral immunity of MSP1 against blood stage parasites has been well documented (8,23,25), no attempt has been made to test its cellular immunity against the liver stage, particularly cytotoxic T lymphocytes, which may play an important role in destroying infected hepatocytes.…”

Section: Discussionmentioning

confidence: 99%

Construction of atetR-IntegratedSalmonella entericaSerovar Typhi CVD908 Strain That Tightly Controls Expression of the Major Merozoite Surface Protein ofPlasmodium falciparumfor Applications in Human Vaccine Production

Qian

2002

Infect Immun

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Attenuated Salmonella strains are an attractive live vector for delivery of a foreign antigen to the human immune system. However, the problem with this vector lies with plasmid segregation and the low level of expression of the foreign gene in vivo when constitutive expression is employed, leading to a diminished immune response. We have established inducible expressions of foreign genes in the Salmonella enterica serovar Typhi CVD908 vaccine strain using the tetracycline response regulatory promoter. To set up this system, a tetracycline repressor (tetR) was integrated into a defined ⌬aroC locus of the chromosome via suicide plasmid pJG12/tetR-neo. To remove the neo gene conferring kanamycin resistance from the locus, a cre expression vector under the control of the tetracycline response promoter was transformed into the clone; expression of the Cre recombinase excised the neo gene and generated the end strain CVD908-tetR. Expression of the luciferase reporter gene in this strain is dependent on the presence of tetracycline in the medium and can be regulated up to 4,773-fold. Moreover, the tightly controlled expression of major merozoite surface protein 1 (MSP1) and parts of Plasmodium falciparum was achieved, and the product yield was increased when the inducible expression system was employed. Inoculation of bacteria harboring plasmid pZE11/MSP1 42 in mice produced the protein in liver and spleen controlled by the inducer. The persistence of the plasmid-carrying bacteria in mice was determined. Peak colonization of both liver and spleen was detected on the third day postinoculation and was followed by a decline in growth curves. After 14 days postinfection, the majority of the bacteria (>90%) recovered from the liver and spleen of the mice retained the plasmid when expression was induced; this clearly indicated that stability of the expression vector in vivo was improved by inducible expression. Establishment of the regulatory system in the vaccine strain may broaden the range of its use by enhancing plasmid stability and expression levels in vivo. Moreover, the availability of the vaccine strain inducibly expressing the entire MSP1 provides possibilities for examining its immunogenicity, particularly the cellular response in animal models.

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“…After another rinsing procedure the infected cells were incubated with complete MEM Rega 3 medium for 58 to 72 hours. Other authors have worked within about the same time range (Suhrbier et al 1989a).…”

Section: Methodsmentioning

confidence: 99%

Plasmodium berghei :susceptibility and growth characteristics of hepatoma cells as hosts for malaria schizonts

François

Desombere

Wéry

1991

Ann. Parasitol. Hum. Comp.

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Three different human hepatoma cell lines (Hep G2, London; Hep G2, Brussels; Mahlavu) have been compared with respect to susceptibility for in vitro infection with Plasmodium berghei sporozoites and subsequent development of mature schizonts and infectious merozoites. The results were very different, even with host cells derived from the same parent line. Both Hep G2 lines were able to function as host cells, but the Mahlavu line was completely refractory. Hep G2 (London) was even more susceptible than the Hep G2-A16 clone. Hepatoma cells harbouring young exoerythrocytic forms permitted their development to mature schi zonts and production of merozoites inside the intraperitoneal cavity of OF1 mice. Pronounced differences in growth parameters of subpopulations of Hep G2 cells were stated as well. Optimal condi tions for in vitro culture of the most suitable cell line were identi fied. Finally, the seeding, plating and cloning efficiencies were determined. Les résultats furent très différents, même entre 2 lignées cellu laires dérivées de la même souche parentale. Les 2 lignées Hep G2 se comportèrent en cellules hôtes, tandis que la lignée Mahlavu se montra totalement réfractaire. Hep G2 (Londres) fut plus sus ceptible que le clône Hep G2-16.Les cellules contenant des formes exoérythrocytaires jeunes per mirent leur développement en schizontes mûrs, dont le transfert dans la cavité péritonéale de souris OF1 entraîna la production de mérozoïtes et une parasitémie.Les sous-populations Hep G2 présentèrent une diversité mar quée de leurs paramètres de croissance. Les conditions optimales pour la culture in vitro de la lignée la plus susceptible furent pré cisées, de même que les indices d'efficacité d'ensemencement, d'éta lement et de clônage.

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Expression of the Precursor of the Major Merozoite Surface Antigens During the Hepatic Stage of Malaria

Cited by 31 publications

References 0 publications

Merozoite Surface Protein 1-Specific Immune Response Is Protective against Exoerythrocytic Forms ofPlasmodium yoelii

Merozoite Surface Protein 1-Specific Immune Response Is Protective against Exoerythrocytic Forms ofPlasmodium yoelii

Construction of atetR-IntegratedSalmonella entericaSerovar Typhi CVD908 Strain That Tightly Controls Expression of the Major Merozoite Surface Protein ofPlasmodium falciparumfor Applications in Human Vaccine Production

Plasmodium berghei :susceptibility and growth characteristics of hepatoma cells as hosts for malaria schizonts

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