Co-display of diverse spike proteins on nanoparticles broadens sarbecovirus neutralizing antibody responses

Brinkkemper, Mitch; Veth, Tim S.; Brouwer, Philip J.M.; Turner, Hannah L.; Poniman, Meliawati; Burger, Judith A.; Bouhuijs, Joey H.; Olijhoek, Wouter; Bontjer, Ilja; Snitselaar, Jonne L.; Caniels, Tom G.; Linden, Cynthia A. van der; Ravichandran, Rashmi; Villaudy, Julien; Velden, Yme U. van der; Sliepen, Kwinten; Gils, Marit J. van; Ward, Andrew B.; King, Neil P.; Heck, Albert J. R.; Sanders, Rogier W.

doi:10.1016/j.isci.2022.105649

Cited by 13 publications

(16 citation statements)

References 57 publications

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“…1C). nsEM of S-2P-I53-50 revealed spherical assemblies densely decorated with Spikes that resembled micrographs previously obtained for sarbecovirus S-I53-50 immunogens (66)(67)(68). RBD-and NTD-I53-50 also formed well-defined nanoparticles with additional densities on the nanoparticle surface, although these were less clearly defined than displayed S-2P due to the smaller size of the RBD and NTD antigens.…”

Section: Production and Characterization Of Nanoparticle Immunogenssupporting

confidence: 84%

Protein nanoparticle vaccines induce potent neutralizing antibody responses against MERS-CoV

Chao,

Sprouse,

Miranda

et al. 2024

Preprint

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Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic betacoronavirus that causes severe and often lethal respiratory illness in humans. The MERS-CoV spike (S) protein is the viral fusogen and the target of neutralizing antibodies, and has therefore been the focus of vaccine design efforts. Currently there are no licensed vaccines against MERS-CoV and only a few candidates have advanced to Phase I clinical trials. Here we developed MERS-CoV vaccines utilizing a computationally designed protein nanoparticle platform that has generated safe and immunogenic vaccines against various enveloped viruses, including a licensed vaccine for SARS-CoV-2. Two-component protein nanoparticles displaying MERS-CoV S-derived antigens induced robust neutralizing antibody responses and protected mice against challenge with mouse-adapted MERS-CoV. Electron microscopy polyclonal epitope mapping and serum competition assays revealed the specificities of the dominant antibody responses elicited by immunogens displaying the prefusion-stabilized S-2P trimer, receptor binding domain (RBD), or N-terminal domain (NTD). An RBD nanoparticle vaccine elicited antibodies targeting multiple non-overlapping epitopes in the RBD, whereas anti-NTD antibodies elicited by the S-2P- and NTD-based immunogens converged on a single antigenic site. Our findings demonstrate the potential of two-component nanoparticle vaccine candidates for MERS-CoV and suggest that this platform technology could be broadly applicable to betacoronavirus vaccine development.

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Section: Production and Characterization Of Nanoparticle Immunogenssupporting

confidence: 84%

Protein nanoparticle vaccines induce potent neutralizing antibody responses against MERS-CoV

Chao,

Sprouse,

Miranda

et al. 2024

Preprint

Self Cite

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“…Several studies have shown that bivalent vaccines can induce a broad-spectrum immune response, which would help prevent infections caused by SARS-CoV-2 variants ( He et al, 2021 ; Yuan et al, 2022 ). Brinkkemper’s study showed that co-display of wild-type and Beta spike proteins of SARS-CoV-2 on self-assembling nanoparticle platform broadens the neutralizing antibody responses ( Brinkkemper et al, 2022 ). Vaccines based on other components, such as S1 or NTD, are also suggested to enhance the broad spectrum of neutralizing antibodies ( Jiang et al, 2021 ; Li et al, 2022 ; Scheaffer et al, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

A bivalent subunit vaccine efficiently produced in Pichia pastoris against SARS-CoV-2 and emerging variants

Xu¹,

Wang²,

Sun³

et al. 2023

Front. Microbiol.

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The emergence of severe acute respiratory syndrome coronavirus type II (SARS-CoV-2) variants have led to a decline in the protection of existing vaccines and antibodies, and there is an urgent need for a broad-spectrum vaccination strategy to reduce the pressure on the prevention and control of the pandemic. In this study, the receptor binding domain (RBD) of the SARS-CoV-2 Beta variant was successfully expressed through a glycoengineered yeast platform. To pursue a more broad-spectrum vaccination strategy, RBD-Beta and RBD-wild type were mixed at the ratio of 1:1 with Al(OH)3 and CpG double adjuvants for the immunization of BALB/c mice. This bivalent vaccine stimulated robust conjugated antibody titers and a broader spectrum of neutralizing antibody titers. These results suggested that a bivalent vaccine of RBD-Beta and RBD-wild type could be a possible broad-spectrum vaccination strategy.

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“…Computationally designed polyhedral assemblies displaying antigens are promising vaccine candidates, triggering robust immune responses. [103][104][105][106][107][108][109][110][111][112][113][114][115][116] Indeed several candidates have advanced to clinical trials, [116][117][118] and more recently a nanoparticle vaccine for COVID-19 has demonstrated the safety and immunogenicity of this technology platform in a phase 1/2 clinical trial, achieving approval for use in South Korea. [119] These protein assemblies have also been used as fluorescence standards, through the display of a defined number of green fluorescent protein molecules, [40,120] and as scaffolds for cryogenic electron microscopy (cryo-EM), through the rigid helical fusion of specific DARPin domains, enabling the analysis of proteins that would otherwise be too small to achieve near-atomic resolution.…”

Section: Current Applications Prevailing Challenges and Rising Opport...mentioning

confidence: 99%

“…First, the exterior surface of the designed polyhedral assemblies can be decorated with a variety of molecules through genetic fusion. Computationally designed polyhedral assemblies displaying antigens are promising vaccine candidates, triggering robust immune responses [103–116] . Indeed several candidates have advanced to clinical trials, [116–118] and more recently a nanoparticle vaccine for COVID‐19 has demonstrated the safety and immunogenicity of this technology platform in a phase 1/2 clinical trial, achieving approval for use in South Korea [119] .…”

Section: Current Applications Prevailing Challenges and Rising Opport...mentioning

confidence: 99%

De Novo Design of Polyhedral Protein Assemblies: Before and After the AI Revolution

et al. 2023

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Self-assembling polyhedral protein biomaterials have gained attention as engineering targets owing to their naturally evolved sophisticated functions, ranging from protecting macromolecules from the environment to spatially controlling biochemical reactions. Precise computational design of de novo protein polyhedra is possible through two main types of approaches: methods from first principles, using physical and geometrical rules, and more recent data-driven methods based on artificial intelligence (AI), including deep learning (DL). Here, we retrospect first principle-and AI-based approaches for designing finite polyhedral protein assemblies, as well as advances in the structure prediction of such assemblies. We further highlight the possible applications of these materials and explore how the presented approaches can be combined to overcome current challenges and to advance the design of functional protein-based biomaterials.

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Co-display of diverse spike proteins on nanoparticles broadens sarbecovirus neutralizing antibody responses

Cited by 13 publications

References 57 publications

Protein nanoparticle vaccines induce potent neutralizing antibody responses against MERS-CoV

Protein nanoparticle vaccines induce potent neutralizing antibody responses against MERS-CoV

A bivalent subunit vaccine efficiently produced in Pichia pastoris against SARS-CoV-2 and emerging variants

De Novo Design of Polyhedral Protein Assemblies: Before and After the AI Revolution

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