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2016 ; 15
(1
): 545
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Bacterial superglue generates a full-length circumsporozoite protein virus-like
particle vaccine capable of inducing high and durable antibody responses
#MMPMID27825348
Janitzek CM
; Matondo S
; Thrane S
; Nielsen MA
; Kavishe R
; Mwakalinga SB
; Theander TG
; Salanti A
; Sander AF
Malar J
2016[Nov]; 15
(1
): 545
PMID27825348
show ga
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.