Journal article
Prediction of Merozoite Surface Protein 1 and Apical Membrane Antigen 1 Vaccine Efficacies against Plasmodium chabaudi Malaria Based on Prechallenge Antibody Responses
Clinical and vaccine immunology, v 16(3), pp 293-302
Mar 2009
PMID: 19116303
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
For the development of blood-stage malaria vaccines, there is a clear need to establish in vitro measures of the antibody-mediated and the cell-mediated immune responses that correlate with protection. In this study, we focused on establishing correlates of antibody-mediated immunity induced by immunization with apical membrane antigen 1 (AMA1) and merozoite surface protein 1
42
(MSP1
42
) subunit vaccines. To do so, we exploited the
Plasmodium chabaudi
rodent model, with which we can immunize animals with both protective and nonprotective vaccine formulations and allow the parasitemia in the challenged animals to peak. Vaccine formulations were varied with regard to the antigen dose, the antigen conformation, and the adjuvant used. Prechallenge antibody responses were evaluated by enzyme-linked immunosorbent assay and were tested for a correlation with protection against nonlethal
P. chabaudi
malaria, as measured by a reduction in the peak level of parasitemia. The analysis showed that neither the isotype profile nor the avidity of vaccine-induced antibodies correlated with protective efficacy. However, high titers of antibodies directed against conformation-independent epitopes were associated with poor vaccine performance and may limit the effectiveness of protective antibodies that recognize conformation-dependent epitopes. We were able to predict the efficacies of the
P. chabaudi
AMA1 (PcAMA1) and
P. chabaudi
MSP1
42
(PcMSP1
42
) vaccines only when the prechallenge antibody titers to both refolded and reduced/alkylated antigens were considered in combination. The relative importance of these two measures of vaccine-induced responses as predictors of protection differed somewhat for the PcAMA1 and the PcMSP1
42
vaccines, a finding confirmed in our final immunization and challenge study. A similar approach to the evaluation of vaccine-induced antibody responses may be useful during clinical trials of
Plasmodium falciparum
AMA1 and MSP1
42
vaccines.
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Details
- Title
- Prediction of Merozoite Surface Protein 1 and Apical Membrane Antigen 1 Vaccine Efficacies against Plasmodium chabaudi Malaria Based on Prechallenge Antibody Responses
- Creators
- Michelle M Lynch - Center for Molecular Parasitology, Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania 19129Amy Cernetich-Ott - Center for Molecular Parasitology, Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania 19129William P Weidanz - Center for Molecular Parasitology, Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania 19129James M Burns - Center for Molecular Parasitology, Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania 19129
- Publication Details
- Clinical and vaccine immunology, v 16(3), pp 293-302
- Publisher
- American Society for Microbiology (ASM)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Web of Science ID
- WOS:000263854200001
- Scopus ID
- 2-s2.0-61949452740
- Other Identifier
- 991014878347604721
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InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Immunology
- Infectious Diseases
- Microbiology