Journal article
Design and Evaluation of Chimeric Plasmodium falciparum Circumsporozoite Protein-Based Malaria Vaccines
Vaccines (Basel), v 12(4), 351
25 Mar 2024
PMID: 38675734
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Efficacy data on two malaria vaccines, RTS,S and R21, targeting
circumsporozoite protein (
CSP), are encouraging. Efficacy may be improved by induction of additional antibodies to neutralizing epitopes outside of the central immunodominant repeat domain of
CSP. We designed four r
CSP-based vaccines in an effort to improve the diversity of the antibody response. We also evaluated
merozoite surface protein 8 (
MSP8) as a malaria-specific carrier protein as an alternative to hepatitis B surface antigen. We measured the magnitude, specificity, subclass, avidity, durability, and efficacy of vaccine-induced antibodies in outbred CD1 mice. In comparison to N-terminal- or C-terminal-focused constructs, immunization with near full-length vaccines, r
CSP (#1) or the chimeric r
CSP/8 (#2), markedly increased the breadth of B cell epitopes recognized covering the N-terminal domain, junctional region, and central repeat. Both r
CSP (#1) and r
CSP/8 (#2) also elicited a high proportion of antibodies to conformation-dependent epitopes in the C-terminus of
CSP. Fusion of
CSP to
MSP8 shifted the specificity of the T cell response away from
CSP toward
MSP8 epitopes. Challenge studies with transgenic
sporozoites expressing
CSP demonstrated high and consistent sterile protection following r
CSP/8 (#2) immunization. Of note, antibodies to conformational C-terminal epitopes were not required for protection. These results indicate that inclusion of the N-terminal domain of
CSP can drive responses to protective, repeat, and non-repeat B cell epitopes and that
MSP8 is an effective carrier for induction of high-titer, durable anti-
CSP antibodies.
Metrics
Details
- Title
- Design and Evaluation of Chimeric Plasmodium falciparum Circumsporozoite Protein-Based Malaria Vaccines
- Creators
- William H Stump - Center for Molecular Parasitology, Department of Microbiology and Immunology, Drexel University College of Medicine, 2900 Queen Lane, Philadelphia, PA 19129, USAHayley J Klingenberg - Drexel UniversityAmy C Ott - Drexel UniversityDonna M Gonzales - Drexel UniversityJames M Burns, Jr - Center for Molecular Parasitology, Department of Microbiology and Immunology, Drexel University College of Medicine, 2900 Queen Lane, Philadelphia, PA 19129, USA
- Publication Details
- Vaccines (Basel), v 12(4), 351
- Publisher
- MDPI
- Grant note
- AI151765 / National Institute of Allergy and Infectious Diseases
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Web of Science ID
- WOS:001211445500001
- Scopus ID
- 2-s2.0-85192357787
- Other Identifier
- 991021872813204721
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InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Immunology
- Medicine, Research & Experimental