Abstract | BACKGROUND:
Malaria, caused by Plasmodium falciparum, continues to have a devastating impact on global health, emphasizing the great need for a malaria vaccine. The circumsporozoite protein (CSP) is an attractive target for a malaria vaccine, and forms a major component of RTS,S, the most clinically advanced malaria vaccine. The clinical efficacy of RTS,S has been moderate, yet has demonstrated the viability of a CSP-based malaria vaccine. In this study, a vaccine comprised of the full-length CSP antigen presented on a virus-like particle (VLP) is produced using a split-intein conjugation system (SpyTag/SpyCatcher) and the immunogenicity is tested in mice. METHODS: Full-length 3d7 CSP protein was genetically fused at the C-terminus to SpyCatcher. The CSP-SpyCatcher antigen was then covalently attached (via the SpyTag/SpyCatcher interaction) to Acinetobacter phage AP205 VLPs which were modified to display one SpyTag per VLP subunit. To evaluate the VLP-display effect, the immunogenicity of the VLP vaccine was tested in mice and compared to a control vaccine containing AP205 VLPs plus unconjugated CSP. RESULTS: Full-length CSP was conjugated at high density (an average of 112 CSP molecules per VLP) to AP205 SpyTag-VLPs. Vaccination of mice with the CSP Spy-VLP vaccine resulted in significantly increased antibody titres over a course of 7 months as compared to the control group (2.6-fold higher at 7 months after immunization). Furthermore, the CSP Spy-VLP vaccine appears to stimulate production of IgG2a antibodies, which has been linked with a more efficient clearing of intracellular parasite infection. CONCLUSION: This study demonstrates that the high-density display of CSP on SpyTag-VLPs, significantly increases the level and quality of the vaccine-induced humoral response, compared to a control vaccine consisting of soluble CSP plus AP205 VLPs. The SpyTag-VLP platform utilized in this study constitutes a versatile and rapid method to develop highly immunogenic vaccines. It might serve as a generic tool for the cost-effective development of effective VLP- vaccines, e.g., against malaria.
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Authors | Christoph M Janitzek, Sungwa Matondo, Susan Thrane, Morten A Nielsen, Reginald Kavishe, Steve B Mwakalinga, Thor G Theander, Ali Salanti, Adam F Sander |
Journal | Malaria journal
(Malar J)
Vol. 15
Issue 1
Pg. 545
(Nov 08 2016)
ISSN: 1475-2875 [Electronic] England |
PMID | 27825348
(Publication Type: Journal Article)
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Chemical References |
- Antibodies, Protozoan
- Drug Carriers
- Immunoglobulin G
- Protozoan Proteins
- Vaccines, Subunit
- Vaccines, Synthetic
- Vaccines, Virus-Like Particle
- circumsporozoite protein, Protozoan
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Topics |
- Acinetobacter
(virology)
- Animals
- Antibodies, Protozoan
(blood)
- Antibody Formation
- Bacteriophages
(chemistry)
- Cell Surface Display Techniques
- Drug Carriers
- Female
- Immunoglobulin G
(blood)
- Mice, Inbred BALB C
- Protozoan Proteins
(genetics, immunology)
- Vaccines, Subunit
(administration & dosage, genetics, immunology)
- Vaccines, Synthetic
(administration & dosage, genetics, immunology)
- Vaccines, Virus-Like Particle
(administration & dosage, genetics, immunology)
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