Advantages and Prospects of Tag/Catcher Mediated Antigen Display on Capsid-Like Particle-Based Vaccines

Abstract

Capsid-like particles (CLPs) are multimeric, repetitive assemblies of recombinant viral capsid proteins, which are highly immunogenic due to their structural similarity to wild-type viruses. CLPs can be used as molecular scaffolds to enable the presentation of soluble vaccine antigens in a similar structural format, which can significantly increase the immunogenicity of the antigen. CLP-based antigen display can be obtained by various genetic and modular conjugation methods. However, these vary in their versatility as well as efficiency in achieving an immunogenic antigen display. Here, we make a comparative review of the major CLP-based antigen display technologies. The Tag/Catcher-AP205 platform is highlighted as a particularly versatile and efficient technology that offers new qualitative and practical advantages in designing modular CLP vaccines. Finally, we discuss how split-protein Tag/Catcher conjugation systems can help to further propagate and enhance modular CLP vaccine designs.

A Vaccine Displaying a Trimeric Influenza-A HA Stem Protein on Capsid-Like Particles Elicits Potent and Long-Lasting Protection in Mice

“…It is well documented that presentation of foreign antigens on the surface of a CLP in a repetitive and ordered format, mimicking that of a native pathogen, can greatly enhance the immune response elicited against the antigen [26,42]. In this study, we set out to test whether CLP presentation could increase the immunogenicity and protective efficacy of a promising HA stem vaccine candidate.…”

“…Due to their size and repetitive surface geometry, which mimic that of live viruses, CLPs induce rapid lymph node drainage, enhanced innate immune activation and strong B-cell receptor cross-linking, leading to potent and long-lasting antibody responses [21,22]. In this study, CLP-display of HA stem was achieved using the Tag/Catcher-AP205 vaccine platform [23][24][25][26]. Upon mixing of the antigen and CLP components, stable antigen:CLP complexes are formed by the spontaneous formation of isopeptide bonds between the reactive tag (SpyTag) and Catcher protein (SpyCatcher), which are genetically fused to the antigen and CLP subunit protein, respectively.…”

“…Upon mixing of the antigen and CLP components, stable antigen:CLP complexes are formed by the spontaneous formation of isopeptide bonds between the reactive tag (SpyTag) and Catcher protein (SpyCatcher), which are genetically fused to the antigen and CLP subunit protein, respectively. Accordingly, the platform can facilitate unidirectional and high density display of even large and complex proteins [26] and has previously been demonstrated to increase immunogenicity and mediate a focused antibody response targeting specific parts of the displayed antigen [27].…”

Field-Effect Sensors for Virus Detection: From Ebola to SARS-CoV-2 and Plant Viral Enhancers

“…Uses as templates for inorganic and synthetic compounds have led to biohybrid materials of convincing properties (Douglas and Young, 1998;Bittner et al, 2013;Vilona et al, 2015;Tiu et al, 2016;Wen and Steinmetz, 2016;Lee et al, 2017;Zhang et al, 2018;Eiben et al, 2019), such as high-capacity battery electrodes or spatially ordered dye ensembles for light-harvesting. If employed as immobilization scaffolds for biomolecules, from peptides and antibodies up to enzymes, plant VLPs exhibit special advantages (Sapsford et al, 2006;Werner et al, 2006;Comellas-Aragones et al, 2007;Minten et al, 2011;Aljabali et al, 2012;Pille et al, 2013;Uhde-Holzem et al, 2016;Roeder et al, 2017;Dickmeis et al, 2018;Koch et al, 2018b;Tian et al, 2018;Yuste-Calvo et al, 2019a;Aves et al, 2020;Park et al, 2020). This has laid the foundation for novel plant virus-supported biocatalytic nanomaterials (Carette et al, 2007;Cardinale et al, 2012;Koch et al, 2015;Besong-Ndika et al, 2016;Cuenca et al, 2016;Brasch et al, 2017;Schwarz et al, 2017;Aumiller et al, 2018;Chakraborti et al, 2019), and for biodetection formats that may serve as blueprints for novel SARS-CoV-2 sensor layouts, as outlined in the following.…”

Special Issue “Virus-Like Particle Vaccines”

“…An important role for VLPs in recent development has been their use as platforms to display antigens. In this context, Ina Balke and Andris Zeltins made an interesting contribution with respect to plant virus-derived VLPs as display platforms [ 2 ] as well as Kara-Lee Aves et al describing the very popular Tag/Catcher system to display antigens on VLPs [ 3 ]. As expected, most of the manuscripts focused on the development of prophylactic vaccines in humans.…”