Malaria Journal | |
Bacterial superglue generates a full-length circumsporozoite protein virus-like particle vaccine capable of inducing high and durable antibody responses | |
Research | |
Thor G. Theander1  Morten A. Nielsen2  Adam F. Sander2  Christoph M. Janitzek2  Ali Salanti2  Susan Thrane2  Steve B. Mwakalinga3  Reginald Kavishe3  Sungwa Matondo3  | |
[1] Centre for Medical Parasitology, Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark;Centre for Medical Parasitology, Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark;Department of Infectious Diseases, Copenhagen University Hospital, Copenhagen, Denmark;Kilimanjaro Christian Medical University College (KCMUCo), Moshi, Tanzania; | |
关键词: Virus-like particle; VLP; Pre-erythrocytic; Malaria vaccine; Circumsporozoite protein; CSP; Spycatcher; Spytag; Bacterial superglue; Split-intein; | |
DOI : 10.1186/s12936-016-1574-1 | |
received in 2016-08-06, accepted in 2016-10-27, 发布年份 2016 | |
来源: Springer | |
【 摘 要 】
BackgroundMalaria, 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.MethodsFull-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.ResultsFull-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.ConclusionThis 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.
【 授权许可】
CC BY
© The Author(s) 2016
【 预 览 】
Files | Size | Format | View |
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RO202311104277994ZK.pdf | 1595KB | download |
【 参考文献 】
- [1]
- [2]
- [3]
- [4]
- [5]
- [6]
- [7]
- [8]
- [9]
- [10]
- [11]
- [12]
- [13]
- [14]
- [15]
- [16]
- [17]
- [18]
- [19]
- [20]
- [21]
- [22]
- [23]
- [24]
- [25]
- [26]
- [27]
- [28]
- [29]
- [30]
- [31]
- [32]
- [33]
- [34]
- [35]
- [36]
- [37]
- [38]
- [39]
- [40]
- [41]
- [42]
- [43]
- [44]
- [45]
- [46]
- [47]
- [48]