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The Capital Region of Denmark - a part of Copenhagen University Hospital
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Improving the malaria transmission-blocking activity of a Plasmodium falciparum 48/45 based vaccine antigen by SpyTag/SpyCatcher mediated virus-like display

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  2. Self-reported immunity and opinions on vaccination of hospital personnel among paediatric healthcare workers in Denmark

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  3. Are refugees arriving in Denmark an under-immunised group for measles? A cross-sectional serology study

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  1. Capsid-like particles decorated with the SARS-CoV-2 receptor-binding domain elicit strong virus neutralization activity

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  2. Antigenic and immunogenic evaluation of permutations of soluble hepatitis C virus envelope protein E2 and E1 antigens

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  3. A Reproducible and Scalable Process for Manufacturing a Pfs48/45 Based Plasmodium falciparum Transmission-Blocking Vaccine

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Malaria is a devastating disease caused by Plasmodium parasites, resulting in almost 0.5 million deaths per year. The Pfs48/45 protein exposed on the P. falciparum sexual stages is one of the most advanced antigen candidates for a transmission-blocking (TB) vaccine in the clinical pipeline. However, it remains essential to identify an optimal vaccine formulation that can facilitate induction of a long-lasting TB anti-Pfs48/45 response. Here we report on the development and evaluation of two Pfs48/45-based virus-like particle (VLP) vaccines generated using the AP205 SpyTag/Catcher VLP system. Two different recombinant proteins (SpyCatcher-R0.6C and SpyCatcher-6C), comprising the Pfs48/45-6C region, were covalently attached to the surface of Spy-tagged Acinetobacter phage AP205 VLPs. Resulting Pfs48/45-VLP complexes appeared as non-aggregated particles of ∼30nm, each displaying an average of 216 (R0.6C) or 291 (6C) copies of the antigens. Both R0.6C and 6C VLP conjugates were strongly reactive with a monoclonal antibody (mAb45.1) targeting a conformational TB Pfs48/45 epitope, suggesting that the TB epitope is accessible for immune recognition on the particles. To select the most suitable vaccine formulation for downstream clinical studies the two VLP vaccines were tested in CD1 mice using different adjuvant formulations. The study demonstrates that VLP-display of R0.6C and 6C significantly increases antigen immunogenicity when using Montanide ISA 720 VG as extrinsic adjuvant.

Original languageEnglish
JournalVaccine
Volume35
Issue number30
Pages (from-to)3726-3732
Number of pages7
ISSN0264-410X
DOIs
Publication statusPublished - 27 Jun 2017

    Research areas

  • Adjuvants, Immunologic, Animals, Antibodies, Protozoan, Antigens, Protozoan, Epitopes, Female, Immunogenicity, Vaccine, Malaria Vaccines, Malaria, Falciparum, Mice, Peptides, Plasmodium falciparum, Protozoan Proteins, Recombinant Proteins, Vaccines, Virus-Like Particle, Journal Article

ID: 52821598