Abstract
Capsid virus-like particles (cVLPs) are used as molecular scaffolds to increase the immunogenicity of displayed antigens. Modular platforms have been developed whereby antigens are attached to the surface of pre-assembled cVLPs. However, it remains unknown to what extent the employed cVLP backbone and conjugation system may influence the immune response elicited against the displayed antigen. Here, we performed a head-to-head comparison of antigen-specific IgG responses elicited by modular cVLP-vaccines differing by their employed cVLP backbone or conjugation system, respectively. Covalent antigen conjugation (i.e., employing the SpyTag/SpyCatcher system) resulted in significantly higher antigen-specific IgG titers compared to when using affinity-based conjugation (i.e., using biotin/streptavidin). The cVLP backbone also influenced the antigen-specific IgG response. Specifically, vaccines based on the bacteriophage AP205 cVLP elicited significantly higher antigen-specific IgG compared to corresponding vaccines using the human papillomavirus major capsid protein (HPV L1) cVLP. In addition, the AP205 cVLP platform mediated induction of antigen-specific IgG with a different subclass profile (i.e., higher IgG2a and IgG2b) compared to HPV L1 cVLP. These results demonstrate that the cVLP backbone and conjugation system can individually affect the IgG response elicited against a displayed antigen. These data will aid the understanding and process of tailoring modular cVLP vaccines to achieve improved immune responses.
Highlights
Life-long protective antibody responses have generally only been achieved by liveattenuated vaccines [1] whose immunogenicity to a large extent has been ascribed to the infectious nature of the inoculum [2]
AP205 capsid virus-like particles (cVLPs) backbones, respectively, to investigate whether the cVLP backbone could influence the IgG response elicited against the displayed antigen
The emergence of modular cVLP-based vaccine platforms creates a need for comparative studies investigating the immunological influence of using specific cVLP backbones and conjugation systems. cVLPs differ in multiple ways which could potentially affect their intrinsic immunogenicity as well as their capacity for antigen display
Summary
Life-long protective antibody responses have generally only been achieved by liveattenuated vaccines [1] whose immunogenicity to a large extent has been ascribed to the infectious nature of the inoculum [2]. HPV L1 cVLPs are highly immunogenic and can induce potent anti-L1 antibody responses lasting for decades, even after a single immunization [2,8,9,10,11]. The structural similarity of cVLPs to native viruses has been established as a reason for their high immunogenicity. Their size (20–200 nm diameter) allow for direct draining to the lymph nodes, and the highly repetitive surface geometry enables efficient
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