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Malar J. 2016 Nov 8;15(1):545.

Bacterial superglue generates a full-length circumsporozoite protein virus-like particle vaccine capable of inducing high and durable antibody responses.

Author information

1
Centre for Medical Parasitology, Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
2
Department of Infectious Diseases, Copenhagen University Hospital, Copenhagen, Denmark.
3
Kilimanjaro Christian Medical University College (KCMUCo), Moshi, Tanzania.
4
Centre for Medical Parasitology, Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark. Salanti@sund.ku.dk.
5
Department of Infectious Diseases, Copenhagen University Hospital, Copenhagen, Denmark. Salanti@sund.ku.dk.
6
Centre for Medical Parasitology, Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark. adamsander@gmail.com.
7
Department of Infectious Diseases, Copenhagen University Hospital, Copenhagen, Denmark. adamsander@gmail.com.

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.

KEYWORDS:

Bacterial superglue; CSP; Circumsporozoite protein; Malaria vaccine; Pre-erythrocytic; Split-intein; Spycatcher; Spytag; VLP; Virus-like particle

PMID:
27825348
PMCID:
PMC5101663
DOI:
10.1186/s12936-016-1574-1
[Indexed for MEDLINE]
Free PMC Article

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