Immune responses against Lewis Y tumor-associated carbohydrate antigen displayed densely on self-assembling nanocarriers

Abstract Fighting smart diseases requires smart vaccines. Novel ways to present protective immunogenic peptide epitopes to human immune systems are needed. Herein, we focus on Self Assembling Protein Nanoparticles (SAPNs) as scaffolds/platforms for vaccine delivery that produce strong immune responses against Toxoplasma gondii in HLA supermotif, transgenic mice. Herein, we present a useful platform to present peptides that elicit CD4+, CD8+ T and B cell immune responses in a core architecture, formed by flagellin, administered in combination with TLR4 ligand-emulsion (GLA-SE) adjuvant. We demonstrate protection of HLA-A*11:01, HLA-A*02:01, and HLA-B*07:02 mice against toxoplasmosis by (i) this novel chimeric polypeptide, containing epitopes that elicit CD8+ T cells, CD4+ T helper cells, and IgG2b antibodies, and (ii) adjuvant activation of innate immune TLR4 and TLR5 pathways. HLA-A*11:01, HLA-A*02:01, and HLA-B*07:02q11 transgenic mouse splenocytes with peptides demonstrated predicted genetic restrictions. This creates a new paradigm-shifting vaccine approach to prevent toxoplasmosis, extendable to other diseases.

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Erratum to: Mechanisms of protective immune responses induced by the Plasmodium falciparum circumsporozoite protein-based, self-assembling protein nanoparticle vaccine

Malaria Journal ◽

10.1186/1475-2875-12-357 ◽

2013 ◽

Vol 12 (1) ◽

Cited By ~ 3

Author(s):

Margaret E McCoy ◽

Hannah E Golden ◽

Tais APF Doll ◽

Yongkun Yang ◽

Stephen A Kaba ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Immune Responses ◽

Circumsporozoite Protein ◽

Self Assembling

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Protein Supramolecular Structures: From Self-Assembly to Nanovaccine Design

Nanomaterials ◽

10.3390/nano10051008 ◽

2020 ◽

Vol 10 (5) ◽

pp. 1008 ◽

Cited By ~ 3

Author(s):

Ximena Zottig ◽

Mélanie Côté-Cyr ◽

Dominic Arpin ◽

Denis Archambault ◽

Steve Bourgault

Keyword(s):

Immune Responses ◽

Self Assembly ◽

Molecular Level ◽

Supramolecular Structures ◽

Atomic Scale ◽

Supramolecular Interactions ◽

Protein Assemblies ◽

Adaptive Immune ◽

Self Assembling ◽

Molecular Specificity

Life-inspired protein supramolecular assemblies have recently attracted considerable attention for the development of next-generation vaccines to fight against infectious diseases, as well as autoimmune diseases and cancer. Protein self-assembly enables atomic scale precision over the final architecture, with a remarkable diversity of structures and functionalities. Self-assembling protein nanovaccines are associated with numerous advantages, including biocompatibility, stability, molecular specificity and multivalency. Owing to their nanoscale size, proteinaceous nature, symmetrical organization and repetitive antigen display, protein assemblies closely mimic most invading pathogens, serving as danger signals for the immune system. Elucidating how the structural and physicochemical properties of the assemblies modulate the potency and the polarization of the immune responses is critical for bottom-up design of vaccines. In this context, this review briefly covers the fundamentals of supramolecular interactions involved in protein self-assembly and presents the strategies to design and functionalize these assemblies. Examples of advanced nanovaccines are presented, and properties of protein supramolecular structures enabling modulation of the immune responses are discussed. Combining the understanding of the self-assembly process at the molecular level with knowledge regarding the activation of the innate and adaptive immune responses will support the design of safe and effective nanovaccines.

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The Lewis-Y Carbohydrate Antigen is Expressed by Many Human Tumors and Can Serve as a Target for Genetically Redirected T cells Despite the Presence of Soluble Antigen in Serum

Journal of Immunotherapy ◽

10.1097/cji.0b013e31819b7c8e ◽

2009 ◽

Vol 32 (3) ◽

pp. 292-301 ◽

Cited By ~ 33

Author(s):

Jennifer A. Westwood ◽

William K. Murray ◽

Melanie Trivett ◽

Nicole M. Haynes ◽

Benjamin Solomon ◽

...

Keyword(s):

T Cells ◽

Carbohydrate Antigen ◽

Human Tumors ◽

Soluble Antigen ◽

Lewis Y

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Correction to “Self-Assembling Nanoparticle Vaccines Displaying the Receptor Binding Domain of SARS-CoV-2 Elicit Robust Protective Immune Responses in Rhesus Monkeys”

Bioconjugate Chemistry ◽

10.1021/acs.bioconjchem.1c00424 ◽

2021 ◽

Author(s):

Heng Li ◽

Lei Guo ◽

Huiwen Zheng ◽

Jing Li ◽

Xin Zhao ◽

...

Keyword(s):

Immune Responses ◽

Receptor Binding ◽

Rhesus Monkeys ◽

Binding Domain ◽

Receptor Binding Domain ◽

Self Assembling

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Abnormal antibodies to self-carbohydrates in SARS-CoV-2 infected patients

10.1101/2020.10.15.341479 ◽

2020 ◽

Author(s):

Dorothy L. Butler ◽

Jeffrey C. Gildersleeve

Keyword(s):

Immune Responses ◽

Neurological Disorders ◽

Critical Role ◽

Carbohydrate Antigen ◽

Sialyl Lewis X ◽

Sialyl Lewis ◽

Global Pandemic ◽

Healthy Control ◽

Blood Group H ◽

Insight Into

AbstractSARS-CoV-2 is a deadly virus that is causing the global pandemic coronavirus disease 2019 (COVID-19). Our immune system plays a critical role in preventing, clearing, and treating the virus, but aberrant immune responses can contribute to deleterious symptoms and mortality. Many aspects of immune responses to SARS-CoV-2 are being investigated, but little is known about immune responses to carbohydrates. Since the surface of the virus is heavily glycosylated, pre-existing antibodies to glycans could potentially recognize the virus and influence disease progression. Furthermore, antibody responses to carbohydrates could be induced, affecting disease severity and clinical outcome. In this study, we used a carbohydrate antigen microarray with over 800 individual components to profile serum anti-glycan antibodies in COVID-19 patients and healthy control subjects. In COVID-19 patients, we observed abnormally high IgG and IgM antibodies to numerous self-glycans, including gangliosides, N-linked glycans, LacNAc-containing glycans, blood group H, and sialyl Lewis X. Some of these anti-glycan antibodies are known to play roles in autoimmune diseases and neurological disorders, which may help explain some of the unusual and prolonged symptoms observed in COVID-19 patients. The detection of antibodies to self-glycans has important implications for using convalescent serum to treat patients, developing safe and effective SARS-CoV-2 vaccines, and understanding the risks of infection. In addition, this study provides new insight into the immune responses to SARS-CoV-2 and illustrates the importance of including host and viral carbohydrate antigens when studying immune responses to viruses.

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Epitope Peptide Amphiphile-Based Nanofiber as an Effective Vaccine for Viral Infectious Diseases

Journal of Nanoscience and Nanotechnology ◽

10.1166/jnn.2020.17655 ◽

2020 ◽

Vol 20 (9) ◽

pp. 5329-5332 ◽

Cited By ~ 1

Author(s):

Yu-Gyeong Kim ◽

Yunsu Lee ◽

Jong-Wha Jung ◽

Hyo-Eon Jin

Keyword(s):

Immune Responses ◽

Enterovirus 71 ◽

Foot And Mouth Disease ◽

Effective Vaccine ◽

Epitope Peptide ◽

Serum Samples ◽

Peptide Amphiphile ◽

Force Microscopy ◽

Self Assembling ◽

Atomic Force

Peptide-based vaccines are relatively safe but have weak immune responses even with an adjuvant. In order to overcome the limitations of peptide-based vaccines, we developed peptide amphiphile (PA)-based nanofibers to enhance the immune responses for preventing enterovirus 71 (EV71) infectious disease (i.e., Hand, Foot, and Mouth Disease). PAs are peptides conjugated with fatty acid alkyl chain and able to self-assemble into various structures including high-aspectratio nanofibers. We designed PAs by coupling EV71 virus particle 1 (VP1) epitope peptides and spacer-crosslinker to the N-terminal of long-chain fatty acids (VP1-PA). PAs then self-assembled into nanofibers at physiological pH (pH 7.4). PA nanofibers were characterized by atomic force microscopy (AFM). For the immunization studies, C57BL/6 mice were injected intraperitoneally (i.p.) with recombinant VP1 with adjuvant (alum), VP1 epitope peptide with or without adjuvant, VP1-PA nanofibers with or without adjuvant, and PBS. To assess the immunogenecity of the VP1-PA nanofibers on serum samples from the immunized mice was analyzed by Western blot for the evaluation of VP1-specific IgG. The PA group showed a higher immune response than the peptide group. We expect that self-assembling VP1-PA based nanofibers as an immune stimulator could enhance immune responses effectively against EV71 infection and overcome the limitations of peptide-based vaccine.

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