Back to Search
Start Over
Plasmodium berghei circumvents immune responses induced by merozoite surface protein 1- and apical membrane antigen 1-based vaccines
- Source :
- PLoS ONE, Vol 5, Iss 10, p e13727 (2010), PLoS ONE
- Publication Year :
- 2010
- Publisher :
- Public Library of Science (PLoS), 2010.
-
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.
- Subjects :
- Plasmodium berghei
Blotting, Western
Protozoan Proteins
lcsh:Medicine
Antigens, Protozoan
Enzyme-Linked Immunosorbent Assay
Biology
Mice
Immune system
Antigen
Immunity
Immunology/Immunity to Infections
Malaria Vaccines
parasitic diseases
Animals
Immunology/Cellular Microbiology and Pathogenesis
Apical membrane antigen 1
Fluorescent Antibody Technique, Indirect
lcsh:Science
Merozoite Surface Protein 1
DNA Primers
Mice, Inbred BALB C
Multidisciplinary
Base Sequence
fungi
lcsh:R
Infectious Diseases/Protozoal Infections
Membrane Proteins
Plasmodium falciparum
biology.organism_classification
Virology
Mice, Inbred C57BL
Infectious Diseases
Infectious Diseases/Neglected Tropical Diseases
Immunology
biology.protein
Female
lcsh:Q
Antibody
Plasmodium yoelii
Research Article
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 5
- Issue :
- 10
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....31107afc269647bccd28881e4a4ead63