Journal article
Evaluation of the Immunogenicity and Vaccine Potential of Recombinant Plasmodium falciparum Merozoite Surface Protein 8
Infection and immunity, v 80(7), pp 2473-2484
Jul 2012
PMID: 22585960
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The C-terminal 19-kDa domain of merozoite surface protein 1 (MSP1
19
) is the target of protective antibodies but alone is poorly immunogenic. Previously, using the
Plasmodium yoelii
murine model, we fused
P. yoelii
MSP1
19
(
Py
MSP1
19
) with full-length
P. yoelii
merozoite surface protein 8 (MSP8). Upon immunization, the MSP8-restricted T cell response provided help for the production of high and sustained levels of protective
Py
MSP1
19
- and
Py
MSP8-specific antibodies. Here, we assessed the vaccine potential of MSP8 of the human malaria parasite,
Plasmodium falciparum
. Distinct from
Py
MSP8,
P. falciparum
MSP8 (
Pf
MSP8) contains an N-terminal asparagine and aspartic acid (Asn/Asp)-rich domain whose function is unknown. Comparative analysis of recombinant full-length
Pf
MSP8 and a truncated version devoid of the Asn/Asp-rich domain,
Pf
MSP8(ΔAsn/Asp), showed that both proteins were immunogenic for T cells and B cells. All T cell epitopes utilized mapped within r
Pf
MSP8(ΔAsn/Asp). The dominant B cell epitopes were conformational and common to both r
Pf
MSP8 and r
Pf
MSP8(ΔAsn/Asp). Analysis of native
Pf
MSP8 expression revealed that
Pf
MSP8 is present intracellularly in late schizonts and merozoites. Following invasion,
Pf
MSP8 is found distributed on the surface of ring- and trophozoite-stage parasites. Consistent with a low and/or transient expression of
Pf
MSP8 on the surface of merozoites,
Pf
MSP8-specific rabbit IgG did not inhibit the
in vitro
growth of
P. falciparum
blood-stage parasites. These studies suggest that the further development of
Pf
MSP8 as a malaria vaccine component should focus on the use of
Pf
MSP8(ΔAsn/Asp) and its conserved, immunogenic T cell epitopes as a fusion partner for protective domains of poor immunogens, including
Pf
MSP1
19
.
Metrics
Details
- Title
- Evaluation of the Immunogenicity and Vaccine Potential of Recombinant Plasmodium falciparum Merozoite Surface Protein 8
- Creators
- James R Alaro - Center for Molecular Parasitology, Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania, USAEvelina Angov - U.S. Military Malaria Research Program, Malaria Vaccine Branch, Walter Reed Army Institute of Research, Silver Spring, Maryland, USAAna M Lopez - Center for Molecular Parasitology, Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania, USAHong Zhou - Malaria Immunology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, USACarole A Long - Center for Molecular Parasitology, Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania, USAJames M Burns - Center for Molecular Parasitology, Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA
- Publication Details
- Infection and immunity, v 80(7), pp 2473-2484
- Publisher
- American Society for Microbiology; 1752 N St., N.W., Washington, DC
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Web of Science ID
- WOS:000305599400023
- Scopus ID
- 2-s2.0-84864800650
- Other Identifier
- 991014878010504721
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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