Innate immune recognition of glycans targets HIV nanoparticle immunogens to germinal centers

Tokatlian, Talar; Read, Benjamin J.; Jones, C. E.; Kulp, Daniel W.; Menis, Sergey; Chang, Jason Y. H.; Steichen, Jon M.; Kumari, Sudha; Allen, Joel D.; Dane, Eric L.; Liguori, Alessia; Sangesland, Maya; Lingwood, Daniel; Crispin, Max; Schief, William R.; Irvine, Darrell J.

doi:10.1126/science.aat9120

Cited by 260 publications

(338 citation statements)

References 37 publications

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“…This phenomenon has been observed on other viral glycoproteins, such as HIV-1 Env 20,26 , and these structures are not particularly prevalent on mammalian glycoproteins 27,28 . Such hybrid-type glycans have been shown to be targeted by anti-HIV antibodies 29 and could also be important for immunogen trafficking since they have mannose-terminating moieties 17 .…”

Section: Localized Impairment To Sars-cov-2 S Glycan Maturationmentioning

confidence: 99%

“…As impaired glycan maturation can be a sensitive reporter of local viral protein architecture 16 , detailed site-specific analysis has emerged as an indicator of native-like architecture and is increasingly used to compare different immunogens and in the monitoring of manufacturing processes. Importantly, in addition to these structural insights, the presence of oligomannose-type glycans on viral spike-based immunogens has also been shown to enhance trafficking of glycoprotein to germinal centers via interaction with lectins such as mannose-binding lectin 17 . It is therefore of considerable importance to understand the glycosylation of recombinant mimetics of the virus spike.…”

Section: Introductionmentioning

confidence: 99%

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Site-specific analysis of the SARS-CoV-2 glycan shield

Watanabe

Allen

Wrapp

et al. 2020

Preprint

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The emergence of the betacoronavirus, SARS-CoV-2 that causes COVID-19, represents a significant threat to global human health. Vaccine development is focused on the principal target of the humoral immune response, the spike (S) glycoprotein, that mediates cell entry and membrane fusion. SARS-CoV-2 S gene encodes 22 N-linked glycan sequons per protomer, which likely play a role in immune evasion and occluding immunogenic protein epitopes. Here, using a site-specific mass spectrometric approach, we reveal the glycan structures on a recombinant SARS-CoV-2 S immunogen. This analysis enables mapping of the glycanprocessing states across the trimeric viral spike. We show how SARS-CoV-2 S glycans differ from typical host glycan processing, which may have implications in viral pathobiology and vaccine design.

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Section: Localized Impairment To Sars-cov-2 S Glycan Maturationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Site-specific analysis of the SARS-CoV-2 glycan shield

Watanabe

Allen

Wrapp

et al. 2020

Preprint

Self Cite

180

181

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“…Much recent effort is being placed on the delivery to, and persistence of antigen in, germinal centers to further promote somatic hypermutation. Continuous delivery of antigen [44,45]**,**, multivalent antigen presentation [46,47]*,* adjuvants, and other technologies, including immune checkpoint modultation to promote germinal center activity, [48] may help overcome the limitations of protein subunits as immunogens. Many of these concepts must now be tested empirically.…”

Section: Somatic Hypermutationmentioning

confidence: 99%

Innovations in structure-based antigen design and immune monitoring for next generation vaccines

Ward

Wilson

2020

Current Opinion in Immunology

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Please cite this article as: Ward AB, Wilson IA, Innovations in structure-based antigen design and immune monitoring for next generation vaccines, J o u r n a l P r e -p r o o f Highligthts Immunofocusing as a strategy for structure-based vaccine design. Structure-based vaccine design for RSV F, influenza HA, HIV-1 Env. Structure-based vaccine design translated into the clinic. AbstractThe recent explosion of atomic-level structures of glycoproteins that comprise the surface antigens of human enveloped viruses, such as RSV, influenza, hepatitis C and HIV, provide tremendous opportunities for rational, structure-based vaccine design. Several concepts in structure-based vaccine design have been put into practice and are are well along preclinical and clinical implementation. Testing of these designed immunogens will provide key insights into the ability to induce the desired immune responses, namely neutralizing antibodies. Many of these immunogens in human clinical trials represent only the first wave of designs and will likely require continued tweaking and elaboration to achieve the ultimate result of ever increasingly breadth and potency. Considerable effort is now being invested in germline targeting, epitope focusing, and improved immune presentation such as multivalent nanoparticle incorporation. This review highlights some of the recent advances in these areas as we prepare for the next generation of immunogens for subsequent rounds of iterative vaccine development.

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“…These constructs have distinct physical structures which can impact the development of the immune response. Reproduced with permission . Copyright 2018, American Association for the Advancement of Science.…”

Section: Biomaterials Provide Control Over the Molecular Properties Omentioning

confidence: 99%

“…The previous studies discussed how anchoring protein antigens to the surface of lipids have allowed for the study of antigen orientation. A related idea centers on controlling molecular antigen properties using self‐assembly of antigen into protein‐based NPs . This strategy has enable study of the distinct immune effects driven by either soluble or particulate forms of antigen.…”

Section: Biomaterials Provide Control Over the Molecular Properties Omentioning

confidence: 99%

Biomaterials as Tools to Decode Immunity

Eppler¹,

Jewell

2019

Advanced Materials

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The immune system has remarkable capabilities to combat disease with exquisite selectivity. This feature has enabled vaccines that provide protection for decades and, more recently, advances in immunotherapies that can cure some cancers. Greater control over how immune signals are presented, delivered, and processed will help drive even more powerful options that are also safe. Such advances will be underpinned by new tools that probe how immune signals are integrated by immune cells and tissues. Biomaterials are valuable resources to support this goal, offering robust, tunable properties. The growing role of biomaterials as tools to dissect immune function in fundamental and translational contexts is highlighted. These technologies can serve as tools to understand the immune system across molecular, cellular, and tissue length scales. A common theme is exploiting biomaterial features to rationally direct how specific immune cells or organs encounter a signal. This precision strategy, enabled by distinct material properties, allows isolation of immunological parameters or processes in a way that is challenging with conventional approaches. The utility of these capabilities is demonstrated through examples in vaccines for infectious disease and cancer immunotherapy, as well as settings of immune regulation that include autoimmunity and transplantation.

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Innate immune recognition of glycans targets HIV nanoparticle immunogens to germinal centers

Cited by 260 publications

References 37 publications

Site-specific analysis of the SARS-CoV-2 glycan shield

Site-specific analysis of the SARS-CoV-2 glycan shield

Innovations in structure-based antigen design and immune monitoring for next generation vaccines

Biomaterials as Tools to Decode Immunity

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