Characterization of the disassembly and reassembly of the HBV glycoprotein surface antigen, a pliable nanoparticle vaccine platform

Gallagher, John R.; Torian, Udana; McCraw, Dustin M.; Harris, Audray K.

doi:10.1016/j.virol.2016.12.025

Cited by 10 publications

(8 citation statements)

References 54 publications

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“…VLP purification was performed on the lysate of the cell pellet, obtained by fermentation; the VLPs were released with the use of detergent, and purified by Ctag affinity chromatography followed by size-exclusion chromatography (see Materials and Methods section for further details). This process led to pure preparations of SpyCatcher::HBsAg, as confirmed by SDS-PAGE (Figure 1A), which shows a pattern typical also for native HBsAg (38), with a final yield of 20 mg/L. Dynamic light scattering (DLS) and electron microscopy (EM) analysis indicated that the particles are homogenous in size, with a diameter of 20-30 nm (Figures 1B,C).…”

Section: Spycatcher::hbsag As Vaccine Carriermentioning

confidence: 61%

A Universal Plug-and-Display Vaccine Carrier Based on HBsAg VLP to Maximize Effective Antibody Response

Marini

Zhou

et al. 2019

Front. Immunol.

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Development of effective malaria vaccines requires delivery platforms to enhance the immunogenicity and efficacy of the target antigens. This is particularly challenging for transmission-blocking malaria vaccines (TBVs), and specifically for those based on the Pfs25 antigen, that need to elicit very high antibody titers to stop the parasite development in the mosquito host and its transmission. Presenting antigens to the immune system on virus-like particles (VLPs) is an efficient way to improve the quantity and quality of the immune response generated. Here we introduce for the first time a new VLP vaccine platform, based on the well-established hepatitis B surface antigen (HBsAg) fused to the SpyCatcher protein, so that the antigen of interest, linked to the SpyTag peptide, can be easily displayed on it (Plug-and-Display technology). As little as 10% of the SpyCatcher::HBsAg VLPs decorated with Pfs25::SpyTag (molar ratio) induces a higher antibody response and transmission-reducing activity in mice compared to the soluble protein, with 50 and 90% of the VLP coupled to the antigen further enhancing the response. Importantly, using this carrier that is a vaccine antigen itself could be beneficial, as we show that anti-HBsAg IgG antibodies are induced without interfering with the Pfs25-specific immune response generated. Furthermore, pre-existing anti-HBsAg immunity does not affect the antigen-specific response to Pfs25::SpyTag-SpyCatcher::HBsAg, suggesting that these VLPs can have a broad use as a vaccine platform.

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Section: Spycatcher::hbsag As Vaccine Carriermentioning

confidence: 61%

A Universal Plug-and-Display Vaccine Carrier Based on HBsAg VLP to Maximize Effective Antibody Response

Marini

Zhou

et al. 2019

Front. Immunol.

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“…Furthermore, other viral VLPs can form glycoprotein particles without their internal capsid structural proteins. For example, the glycoproteins of hepatitis B virus can form particles without the internal structural capsid protein 37 . Likewise, glycoproteins of Zika virus can form particles without expression of the capsid protein 38 .…”

Section: Discussionmentioning

confidence: 99%

Structural analysis of influenza vaccine virus-like particles reveals a multicomponent organization

McCraw

Gallagher

Torian

et al. 2018

Sci Rep

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Influenza virus continues to be a major health problem due to the continually changing immunodominant head regions of the major surface glycoprotein, hemagglutinin (HA). However, some emerging vaccine platforms designed by biotechnology efforts, such as recombinant influenza virus-like particles (VLPs) have been shown to elicit protective antibodies to antigenically different influenza viruses. Here, using biochemical analyses and cryo-electron microscopy methods coupled to image analysis, we report the composition and 3D structural organization of influenza VLPs of the 1918 pandemic influenza virus. HA molecules were uniformly distributed on the VLP surfaces and the conformation of HA was in a prefusion state. Moreover, HA could be bound by antibody targeting conserved epitopes in the stem region of HA. Taken together, our analysis suggests structural parameters that may be important for VLP biotechnology such as a multi-component organization with (i) an outer component consisting of prefusion HA spikes on the surfaces, (ii) a VLP membrane with HA distribution permitting stem epitope display, and (iii) internal structural components.

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“…Prediction software has been developed for the purpose of recognizing both conformational and linear BCR epitopes, indicating that receptors do preferentially interact with epitopes displaying certain quantifiable properties (i.e., patterns in sequence) (108). However, the utility of these predictions when considering PBV design is limited due to small and inconsistent datasets, difficulties predicting antigen 3D structure, and the structural heterogeneity exhibited by some PBVs (108)(109)(110)(111). The last consideration, epitope size, consists of constraints that are somewhat vague.…”

Section: Mechanisms Behind Bcr Recognition Of Pbvmentioning

confidence: 99%

Designs of Antigen Structure and Composition for Improved Protein-Based Vaccine Efficacy

et al. 2020

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Today, vaccinologists have come to understand that the hallmark of any protective immune response is the antigen. However, it is not the whole antigen that dictates the immune response, but rather the various parts comprising the whole that are capable of influencing immunogenicity. Protein-based antigens hold particular importance within this structural approach to understanding immunity because, though different molecules can serve as antigens, only proteins are capable of inducing both cellular and humoral immunity. This fact, coupled with the versatility and customizability of proteins when considering vaccine design applications, makes protein-based vaccines (PBVs) one of today's most promising technologies for artificially inducing immunity. In this review, we follow the development of PBV technologies through time and discuss the antigen-specific receptors that are most critical to any immune response: pattern recognition receptors, B cell receptors, and T cell receptors. Knowledge of these receptors and their ligands has become exceptionally valuable in the field of vaccinology, where today it is possible to make drastic modifications to PBV structure, from primary to quaternary, in order to promote recognition of target epitopes, potentiate vaccine immunogenicity, and prevent antigen-associated complications. Additionally, these modifications have made it possible to control immune responses by modulating stability and targeting PBV to key immune cells. Consequently, careful consideration should be given to protein structure when designing PBVs in the future in order to potentiate PBV efficacy.

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Characterization of the disassembly and reassembly of the HBV glycoprotein surface antigen, a pliable nanoparticle vaccine platform

Cited by 10 publications

References 54 publications

A Universal Plug-and-Display Vaccine Carrier Based on HBsAg VLP to Maximize Effective Antibody Response

A Universal Plug-and-Display Vaccine Carrier Based on HBsAg VLP to Maximize Effective Antibody Response

Structural analysis of influenza vaccine virus-like particles reveals a multicomponent organization

Designs of Antigen Structure and Composition for Improved Protein-Based Vaccine Efficacy

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