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Journal article
A Chimeric Plasmodium falciparum Merozoite Surface Protein Vaccine Induces High Titers of Parasite Growth Inhibitory Antibodies
Infection and immunity, v 81(10), pp 3843-3854
01 Oct 2013
PMID: 23897613
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The C-terminal 19-kDa domain of
Plasmodium falciparum
merozoite surface protein 1 (
Pf
MSP1
19
) is an established target of protective antibodies. However, clinical trials of
Pf
MSP1
42
, a leading blood-stage vaccine candidate which contains the protective epitopes of
Pf
MSP1
19
, revealed suboptimal immunogenicity and efficacy. Based on proof-of-concept studies in the
Plasmodium yoelii
murine model, we produced a chimeric vaccine antigen containing recombinant
Pf
MSP1
19
(r
Pf
MSP1
19
) fused to the N terminus of
P. falciparum
merozoite surface protein 8 that lacked its low-complexity Asn/Asp-rich domain, r
Pf
MSP8 (ΔAsn/Asp). Immunization of mice with the chimeric r
Pf
MSP1/8 vaccine elicited strong T cell responses to conserved epitopes associated with the r
Pf
MSP8 (ΔAsn/Asp) fusion partner. While specific for
Pf
MSP8, this T cell response was adequate to provide help for the production of high titers of antibodies to both
Pf
MSP1
19
and r
Pf
MSP8 (ΔAsn/Asp) components. This occurred with formulations adjuvanted with either Quil A or with Montanide ISA 720 plus CpG oligodeoxynucleotide (ODN) and was observed in both inbred and outbred strains of mice.
Pf
MSP1/8-induced antibodies were highly reactive with two major alleles of
Pf
MSP1
19
(FVO and 3D7). Of particular interest, immunization with
Pf
MSP1/8 elicited higher titers of
Pf
MSP1
19
-specific antibodies than a combined formulation of r
Pf
MSP1
42
and r
Pf
MSP8 (ΔAsn/Asp). As a measure of functionality,
Pf
MSP1/8-specific rabbit IgG was shown to potently inhibit the
in vitro
growth of blood-stage parasites of the FVO and 3D7 strains of
P. falciparum
. These data support the further testing and evaluation of this chimeric
Pf
MSP1/8 antigen as a component of a multivalent vaccine for
P. falciparum
malaria.
Metrics
Details
- Title
- A Chimeric Plasmodium falciparum Merozoite Surface Protein Vaccine Induces High Titers of Parasite Growth Inhibitory Antibodies
- Creators
- James R. Alaro - Drexel UniversityAndrea Partridge - Drexel UniversityKazutoyo Miura - National Institute of Allergy and Infectious DiseasesAbabacar Diouf - National Institute of Allergy and Infectious DiseasesAna M. Lopez - Drexel UniversityEvelina Angov - Walter Reed Army Institute of ResearchCarole A. Long - Drexel UniversityJames M. Burns - Drexel University
- Publication Details
- Infection and immunity, v 81(10), pp 3843-3854
- Publisher
- American Society for Microbiology
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Web of Science ID
- WOS:000324528700035
- Scopus ID
- 2-s2.0-84884371877
- Other Identifier
- 991019168879404721
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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