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Plasmodium berghei circumvents immune responses induced by merozoite surface protein 1- and apical membrane antigen 1-based vaccines.

Yoshida S, Nagumo H, Yokomine T, Araki H, Suzuki A, Matsuoka H - PLoS ONE (2010)

Bottom Line: Similarly, neither P. berghei MSP1(19)- nor AMA1-BBV was effective against P. berghei.P. berghei completely circumvents immune responses induced by MSP1(19)- and AMA1-based vaccines, suggesting that P. berghei possesses additional molecules and/or mechanisms that circumvent the host's immune responses to MSP1(19) and AMA1, which are lacking in P. yoelii.Although it is not known whether P. falciparum shares these escape mechanisms with P. berghei, P. berghei and its transgenic models may have potential as useful tools for identifying and evaluating new blood-stage vaccine candidate antigens for P. falciparum.

View Article: PubMed Central - PubMed

Affiliation: Division of Medical Zoology, Department of Infection and Immunity, Jichi Medical University, Tochigi, Japan. shigeto@p.kanazawa-u.ac.jp

ABSTRACT

Background: Two current leading malaria blood-stage vaccine candidate antigens for Plasmodium falciparum, the C-terminal region of merozoite surface protein 1 (MSP1(19)) and apical membrane antigen 1 (AMA1), have been prioritized because of outstanding protective efficacies achieved in a rodent malaria Plasmodium yoelii model. However, P. falciparum vaccines based on these antigens have had disappointing outcomes in clinical trials. Discrepancies in the vaccine efficacies observed between the P. yoelii model and human clinical trials still remain problematic.

Methodology and results: In this study, we assessed the protective efficacies of a series of MSP1(19)- and AMA1-based vaccines using the P. berghei rodent malarial parasite and its transgenic models. Immunization of mice with a baculoviral-based vaccine (BBV) expressing P. falciparum MSP1(19) induced high titers of PfMSP1(19)-specific antibodies that strongly reacted with P. falciparum blood-stage parasites. However, no protection was achieved following lethal challenge with transgenic P. berghei expressing PfMSP1(19) in place of native PbMSP1(19). Similarly, neither P. berghei MSP1(19)- nor AMA1-BBV was effective against P. berghei. In contrast, immunization with P. yoelii MSP1(19)- and AMA1-BBVs provided 100% and 40% protection, respectively, against P. yoelii lethal challenge. Mice that naturally acquired sterile immunity against P. berghei became cross-resistant to P. yoelii, but not vice versa.

Conclusion: This is the first study to address blood-stage vaccine efficacies using both P. berghei and P. yoelii models at the same time. P. berghei completely circumvents immune responses induced by MSP1(19)- and AMA1-based vaccines, suggesting that P. berghei possesses additional molecules and/or mechanisms that circumvent the host's immune responses to MSP1(19) and AMA1, which are lacking in P. yoelii. Although it is not known whether P. falciparum shares these escape mechanisms with P. berghei, P. berghei and its transgenic models may have potential as useful tools for identifying and evaluating new blood-stage vaccine candidate antigens for P. falciparum.

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Kinetics of PfMSP119-specific antibody titers and parasitemia during the course of infection.Groups of mice were non-immunized or immunized either i.m. or i.n. with AcNPV-PfMSP119surf, and then challenged i.v. with 103 Pb-PfM19 pRBC. Parasitemia was monitored daily 4 days after challenge and sera were collected periodically post-challenge to measure antibody titers. The bar chart indicates PfMSP119-specific antibody titers on the left vertical axis. The line graph indicates the course of parasitemia (%) on the right vertical axis. (+), death.
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pone-0013727-g002: Kinetics of PfMSP119-specific antibody titers and parasitemia during the course of infection.Groups of mice were non-immunized or immunized either i.m. or i.n. with AcNPV-PfMSP119surf, and then challenged i.v. with 103 Pb-PfM19 pRBC. Parasitemia was monitored daily 4 days after challenge and sera were collected periodically post-challenge to measure antibody titers. The bar chart indicates PfMSP119-specific antibody titers on the left vertical axis. The line graph indicates the course of parasitemia (%) on the right vertical axis. (+), death.

Mentions: To examine whether natural boosting of PfMSP-119-specific antibodies was induced, the kinetics of the PfMSP119-specific antibody titers and parasitemia during the course of infection were determined. PfMSP119-specific antibodies induced by i.m. and i.n. immunization with AcNPV-PfMSP119surf increased 2.7- and 4.2-fold 11 days after challenge infection (Figure 2), indicating natural boosting by challenge infection. However, the immunized groups died with high levels of parasitemia and anemia but without signs of cerebral malaria, which is similar to the non-immunized group.


Plasmodium berghei circumvents immune responses induced by merozoite surface protein 1- and apical membrane antigen 1-based vaccines.

Yoshida S, Nagumo H, Yokomine T, Araki H, Suzuki A, Matsuoka H - PLoS ONE (2010)

Kinetics of PfMSP119-specific antibody titers and parasitemia during the course of infection.Groups of mice were non-immunized or immunized either i.m. or i.n. with AcNPV-PfMSP119surf, and then challenged i.v. with 103 Pb-PfM19 pRBC. Parasitemia was monitored daily 4 days after challenge and sera were collected periodically post-challenge to measure antibody titers. The bar chart indicates PfMSP119-specific antibody titers on the left vertical axis. The line graph indicates the course of parasitemia (%) on the right vertical axis. (+), death.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2965677&req=5

pone-0013727-g002: Kinetics of PfMSP119-specific antibody titers and parasitemia during the course of infection.Groups of mice were non-immunized or immunized either i.m. or i.n. with AcNPV-PfMSP119surf, and then challenged i.v. with 103 Pb-PfM19 pRBC. Parasitemia was monitored daily 4 days after challenge and sera were collected periodically post-challenge to measure antibody titers. The bar chart indicates PfMSP119-specific antibody titers on the left vertical axis. The line graph indicates the course of parasitemia (%) on the right vertical axis. (+), death.
Mentions: To examine whether natural boosting of PfMSP-119-specific antibodies was induced, the kinetics of the PfMSP119-specific antibody titers and parasitemia during the course of infection were determined. PfMSP119-specific antibodies induced by i.m. and i.n. immunization with AcNPV-PfMSP119surf increased 2.7- and 4.2-fold 11 days after challenge infection (Figure 2), indicating natural boosting by challenge infection. However, the immunized groups died with high levels of parasitemia and anemia but without signs of cerebral malaria, which is similar to the non-immunized group.

Bottom Line: Similarly, neither P. berghei MSP1(19)- nor AMA1-BBV was effective against P. berghei.P. berghei completely circumvents immune responses induced by MSP1(19)- and AMA1-based vaccines, suggesting that P. berghei possesses additional molecules and/or mechanisms that circumvent the host's immune responses to MSP1(19) and AMA1, which are lacking in P. yoelii.Although it is not known whether P. falciparum shares these escape mechanisms with P. berghei, P. berghei and its transgenic models may have potential as useful tools for identifying and evaluating new blood-stage vaccine candidate antigens for P. falciparum.

View Article: PubMed Central - PubMed

Affiliation: Division of Medical Zoology, Department of Infection and Immunity, Jichi Medical University, Tochigi, Japan. shigeto@p.kanazawa-u.ac.jp

ABSTRACT

Background: Two current leading malaria blood-stage vaccine candidate antigens for Plasmodium falciparum, the C-terminal region of merozoite surface protein 1 (MSP1(19)) and apical membrane antigen 1 (AMA1), have been prioritized because of outstanding protective efficacies achieved in a rodent malaria Plasmodium yoelii model. However, P. falciparum vaccines based on these antigens have had disappointing outcomes in clinical trials. Discrepancies in the vaccine efficacies observed between the P. yoelii model and human clinical trials still remain problematic.

Methodology and results: In this study, we assessed the protective efficacies of a series of MSP1(19)- and AMA1-based vaccines using the P. berghei rodent malarial parasite and its transgenic models. Immunization of mice with a baculoviral-based vaccine (BBV) expressing P. falciparum MSP1(19) induced high titers of PfMSP1(19)-specific antibodies that strongly reacted with P. falciparum blood-stage parasites. However, no protection was achieved following lethal challenge with transgenic P. berghei expressing PfMSP1(19) in place of native PbMSP1(19). Similarly, neither P. berghei MSP1(19)- nor AMA1-BBV was effective against P. berghei. In contrast, immunization with P. yoelii MSP1(19)- and AMA1-BBVs provided 100% and 40% protection, respectively, against P. yoelii lethal challenge. Mice that naturally acquired sterile immunity against P. berghei became cross-resistant to P. yoelii, but not vice versa.

Conclusion: This is the first study to address blood-stage vaccine efficacies using both P. berghei and P. yoelii models at the same time. P. berghei completely circumvents immune responses induced by MSP1(19)- and AMA1-based vaccines, suggesting that P. berghei possesses additional molecules and/or mechanisms that circumvent the host's immune responses to MSP1(19) and AMA1, which are lacking in P. yoelii. Although it is not known whether P. falciparum shares these escape mechanisms with P. berghei, P. berghei and its transgenic models may have potential as useful tools for identifying and evaluating new blood-stage vaccine candidate antigens for P. falciparum.

Show MeSH
Related in: MedlinePlus