Bacterial superglue enables easy development of efficient virus-like particle based vaccines
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- Bacterial superglue enables easy development of efficient virus-like particle based vaccines
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Susan Thrane, Christoph M Janitzek, Sungwa Matondo, Mafalda dos Santos Marques Resende, Tobias Gustavsson, Willem Adriaan De Jongh, Stine Clemmensen, Will Roeffen, Marga van de Vegte-Bolmer, Geert Jan van Gemert, Robert Sauerwein, John T Schiller, Morten A Nielsen, Thor G Theander, Ali Salanti, Adam Frederik Sander Pedersen
RESULTS: Genetic fusion of SpyTag or SpyCatcher to the N-terminus and/or C-terminus of the Acinetobacter phage AP205 capsid protein resulted in formation of stable, nonaggregated VLPs expressing one SpyCatcher, one SpyTag or two SpyTags per capsid protein. Mixing of spy-VLPs with eleven different vaccine antigens fused to SpyCatcher or SpyTag resulted in formation of antigen-VLP complexes with coupling efficiencies (% occupancy of total VLP binding sites) ranging from 22-88 %. In mice, spy-VLP vaccines presenting the malaria proteins Pfs25 or VAR2CSA markedly increased antibody titer, affinity, longevity and functional efficacy compared to corresponding vaccines employing monomeric proteins. The spy-VLP vaccines also effectively broke B cell self-tolerance and induced potent and durable antibody responses upon vaccination with cancer or allergy-associated self-antigens (PD-L1, CTLA-4 and IL-5).
CONCLUSIONS: The spy-VLP system constitutes a versatile and rapid method to develop highly immunogenic VLP-based vaccines. Our data provide proof-of-concept for the technology's ability to present complex vaccine antigens to the immune system and elicit robust functional antibody responses as well as to efficiently break B cell self-tolerance. The spy-VLP-system may serve as a generic tool for the cost-effective development of effective VLP-vaccines against both infectious- and non-communicable diseases and could facilitate rapid and unbiased screening of vaccine candidate antigens.
|Tidsskrift||Journal of Nanobiotechnology|
|Status||Udgivet - 27 apr. 2016|
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