Virus-like particle-display of the enterotoxigenic Escherichia coli heat-stable toxoid STh-A14T elicits neutralizing antibodies in mice

Govasli, Morten L.; Díaz, Yuleima; Puntervoll, Pål

doi:10.1016/j.vaccine.2019.09.004

Cited by 21 publications

(24 citation statements)

References 40 publications

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“…To develop nanoparticle vaccine immunogens, rapid and efficient methods would help produce nanoparticle scaffolds that can be mixed and matched with different immunogens. Previous efforts utilizing the spontaneous isopeptide bond formation with the SpyTag:SpyCatcher system for nanoparticle surface display of immunogens [11][12][13][14][15][16] have proven the versatility of this system for antigen display. However, none of these previously published reports utilized mammalian expression allowing for post-translational modifications, such as N-linked glycosylation.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, many viral antigens require glycosylation to be stably expressed and correctly folded. Although several studies have described plug-and-play nanoparticle systems [11][12][13][14][15][16] , many use prokaryotic expression systems, which are not suitable to produce correctly glycosylated antigens. Furthermore, N-glycans can be manipulated in immunogen design to selectively occlude unwanted epitopes as well as to improve the solubility and stability of immunogens [17][18][19] .…”

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confidence: 99%

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A platform incorporating trimeric antigens into self-assembling nanoparticles reveals SARS-CoV-2-spike nanoparticles to elicit substantially higher neutralizing responses than spike alone

Zhang

Chao

Tsybovsky

et al. 2020

Sci Rep

102

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Antigens displayed on self-assembling nanoparticles can stimulate strong immune responses and have been playing an increasingly prominent role in structure-based vaccines. However, the development of such immunogens is often complicated by inefficiencies in their production. To alleviate this issue, we developed a plug-and-play platform using the spontaneous isopeptide-bond formation of the SpyTag:SpyCatcher system to display trimeric antigens on self-assembling nanoparticles, including the 60-subunit Aquifex aeolicus lumazine synthase (LuS) and the 24-subunit Helicobacter pylori ferritin. LuS and ferritin coupled to SpyTag expressed well in a mammalian expression system when an N-linked glycan was added to the nanoparticle surface. The respiratory syncytial virus fusion (F) glycoprotein trimer—stabilized in the prefusion conformation and fused with SpyCatcher—could be efficiently conjugated to LuS-SpyTag or ferritin-SpyTag, enabling multivalent display of F trimers with prefusion antigenicity. Similarly, F-glycoprotein trimers from human parainfluenza virus-type 3 and spike-glycoprotein trimers from SARS-CoV-2 could be displayed on LuS nanoparticles with decent yield and antigenicity. Notably, murine vaccination with 0.08 µg of SARS-CoV-2 spike-LuS nanoparticle elicited similar neutralizing responses as 2.0 µg of spike, which was ~ 25-fold higher on a weight-per-weight basis. The versatile platform described here thus allows for multivalent plug-and-play presentation on self-assembling nanoparticles of trimeric viral antigens, with SARS-CoV-2 spike-LuS nanoparticles inducing particularly potent neutralizing responses.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

A platform incorporating trimeric antigens into self-assembling nanoparticles reveals SARS-CoV-2-spike nanoparticles to elicit substantially higher neutralizing responses than spike alone

Zhang

Chao

Tsybovsky

et al. 2020

Sci Rep

102

View full text Add to dashboard Cite

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“…Even though AP205 VLPs are under investigation as carrier for various vaccine candidates (24)(25)(26)(27)(28)(29), no safety data in humans is available, and such lack of clinical information can slow down the development of new vaccines based on this VLP platform. By contrast, using a VLP with a well-established safety profile as a vaccine scaffold could accelerate the pre-clinical to clinical transition.…”

Section: Introductionmentioning

confidence: 99%

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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“…The Tag/Catcher-AP205 platform was developed by genetic incorporation of the SpyTag [39] and SpyCatcher [39,51] into the capsid protein of the Acinetobacter phage AP205, yielding particles of 180 subunits with a diameter of approximately 36 nm and 43 nm, respectively. Since its development, the Tag/Catcher-AP205 platform has been utilized to display structurally and functionally diverse vaccine antigens, ranging in size from small peptides (e.g., toxins of 19 amino acids [71]) to large (>300 kDa) trimeric proteins [72]. These studies have repeatedly demonstrated a remarkable ability to achieve complete and even decoration of the CLP surface, with coupling efficiencies reaching 100% for smaller vaccine antigens, which are not limited by steric hindrance.…”

Section: Split-protein (Tag/catcher) Conjugationmentioning

confidence: 99%

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

Aves

Goksøyr

Sander

2020

Viruses

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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.

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Virus-like particle-display of the enterotoxigenic Escherichia coli heat-stable toxoid STh-A14T elicits neutralizing antibodies in mice

Cited by 21 publications

References 40 publications

A platform incorporating trimeric antigens into self-assembling nanoparticles reveals SARS-CoV-2-spike nanoparticles to elicit substantially higher neutralizing responses than spike alone

A platform incorporating trimeric antigens into self-assembling nanoparticles reveals SARS-CoV-2-spike nanoparticles to elicit substantially higher neutralizing responses than spike alone

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

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

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