Prediction of Merozoite Surface Protein 1 and Apical Membrane Antigen 1 Vaccine Efficacies againstPlasmodium chabaudiMalaria Based on Prechallenge Antibody Responses
| Autor: | William P. Weidanz, Michelle M. Lynch, James M. Burns, Amy Cernetich-Ott |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Male
Microbiology (medical) Clinical Biochemistry Immunology Protozoan Proteins Antibodies Protozoan Antigens Protozoan Enzyme-Linked Immunosorbent Assay Parasitemia Epitope Plasmodium chabaudi Mice Adjuvants Immunologic Antigen Malaria Vaccines parasitic diseases medicine Animals Immunology and Allergy Apical membrane antigen 1 Merozoite surface protein Merozoite Surface Protein 1 biology Vaccination Antibody titer Membrane Proteins Plasmodium falciparum Vaccine Research biology.organism_classification medicine.disease Virology Malaria Mice Inbred C57BL Epitopes B-Lymphocyte Biomarkers |
| Zdroj: | Clinical and Vaccine Immunology. 16:293-302 |
| ISSN: | 1556-679X 1556-6811 |
| DOI: | 10.1128/cvi.00230-08 |
| Popis: | 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 142(MSP142) subunit vaccines. To do so, we exploited thePlasmodium chabaudirodent 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 nonlethalP. chabaudimalaria, 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 theP. chabaudiAMA1 (PcAMA1) andP. chabaudiMSP142(PcMSP142) 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 PcMSP142vaccines, 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 ofPlasmodium falciparumAMA1 and MSP142vaccines. |
| Databáze: | OpenAIRE |
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