Journal article
Immunization against Plasmodium chabaudi malaria using combined formulations of apical membrane antigen-1 and merozoite surface protein-1
Vaccine, v 21(17-18), pp 1843-1852
16 May 2003
PMID: 12706668
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The control of Plasmodium falciparum malaria by vaccination will require immunization with multiple parasite antigens effectively formulated in combination. In this regard, proteins expressed on the surface of blood-stage merozoites are attractive as vaccine targets given their functional importance in the invasion of erythrocytes and accessibility to serum antibodies. We have utilized a Plasmodium chabaudi vaccine model to begin to evaluate the efficacy of immunization with combined formulations of apical membrane antigen-1 (AMA-1) and merozoite surface protein-1 (MSP-1). Using a pET/T7 RNA polymerase bacterial expression system, we have expressed, purified and refolded recombinant antigens representing the 54 kDa ectodomain of Pc AMA-1 and the 42 kDa C-terminus of Pc MSP-1. Immunization with recombinant Pc AMA-1+Pc MSP-1(42) induced a high level of protection against P. chabaudi malaria with protective efficacy varying with antigen dose, choice of adjuvant, and immunization protocol. Based on the reduction of P. chabaudi parasitemia, Alum proved effective for use with the combination of Pc AMA-1 and Pc MSP-1(42). The use of Quil A was similarly effective with single or combined antigen immunizations, particularly with low antigen dose. In general, serological analysis of prechallenge sera indicated a dominant IgG1 response. For a given formulation, immunization with the combination of Pc AMA-1 and Pc MSP-1(42) elicited IgG responses comparable to those observed following immunization with each antigen alone. However, prechallenge antibody titers alone were not predictive of protective efficacy. While Pc AMA-1 and Pc MSP-1(42) can be effectively formulated in combination, further study is needed to define measurable parameters of protective T cell and B cell responses induced by Pc AMA-1+Pc MSP-1(42) that are predictive of vaccine efficacy.
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Details
- Title
- Immunization against Plasmodium chabaudi malaria using combined formulations of apical membrane antigen-1 and merozoite surface protein-1
- Creators
- James M Burns, Jr - Department of Microbiology and Immunology, Drexel University College of Medicine, 2900 Queen Lane, Philadelphia, PA 19129, USA. jburns@drexel.eduPatrick R FlahertyMargarita M RomeroWilliam P Weidanz
- Publication Details
- Vaccine, v 21(17-18), pp 1843-1852
- Publisher
- Elsevier; Netherlands
- Grant note
- AI49585 / NIAID NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Web of Science ID
- WOS:000183100200007
- Scopus ID
- 2-s2.0-0037449076
- Other Identifier
- 991014878251104721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Immunology
- Medicine, Research & Experimental