Vaccination with self-adjuvanted protein nanoparticles provides protection against lethal influenza challenge

Khan, Mazhar I.

doi:10.1016/j.nano.2016.08.030

Cited by 63 publications

(68 citation statements)

References 33 publications

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“…Our data showed potent immunogenicity (high IFN-γ secretion) when splenocytes were stimulated by these peptides through immunization in vivo, and then exposure in vitro. In separate studies, 24 we found that SAPN, which contains flagellin, protected better against influenza than SAPN without flagellin. This flagellin scaffold then became our SAPN platform going forward.…”

Section: Discussionmentioning

confidence: 78%

“…Earlier logic for inclusion of flagellin as adjuvant and scaffold came from work with malaria (http://www.internationalinnovation.com/build/wp-content/uploads/2016/05/David_Lanar_Intl_Innovation_ Infectious_Diseases_Research_Media_LR.pdf), 19 as well as with influenza. 24 Computer model of the prototype. The core particle composed of the pentameric and trimeric coiled coils is shown in green and blue, respectively.…”

Section: In Vitro Tlr5 Stimulationmentioning

confidence: 99%

“…This approach was also used in our work with influenza. 24 This work suggested that flagellin would be helpful as a scaffold and immunogen in our newest T. gondii work.…”

Section: Introductionmentioning

confidence: 97%

“…In our previous studies with T. gondii, we constructed SAPNs displaying the dense granule epitope (GRA7 [20][21][22][23][24][25][26][27][28] ) and pan-DR binding epitope PADRE. 26 We evaluated these vaccine components in HLA-B*0702 transgenic mice.…”

Section: Introductionmentioning

confidence: 99%

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Protein nanovaccine confers robust immunity against Toxoplasma

Bissati

Zhou

Paulillo³

et al. 2017

npj Vaccines

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We designed and produced a self-assembling protein nanoparticle. This self-assembling protein nanoparticle contains five CD8+ HLA-A03-11 supertypes-restricted epitopes from antigens expressed during Toxoplasma gondii’s lifecycle, the universal CD4+ T cell epitope PADRE, and flagellin as a scaffold and TLR5 agonist. These CD8+ T cell epitopes were separated by N/KAAA spacers and optimized for proteasomal cleavage. Self-assembling protein nanoparticle adjuvanted with TLR4 ligand-emulsion GLA-SE were evaluated for their efficacy in inducing IFN-γ responses and protection of HLA-A*1101 transgenic mice against T. gondii. Immunization, using self-assembling protein nanoparticle-GLA-SE, activated CD8+ T cells to produce IFN-γ. Self-assembling protein nanoparticle-GLA-SE also protected HLA-A*1101 transgenic mice against subsequent challenge with Type II parasites. Hence, combining CD8+ T cell-eliciting peptides and PADRE into a multi-epitope protein that forms a nanoparticle, administered with GLA-SE, leads to efficient presentation by major histocompatibility complex Class I and II molecules. Furthermore, these results suggest that activation of TLR4 and TLR5 could be useful for development of vaccines that elicit T cells to prevent toxoplasmosis in humans.

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Section: Discussionmentioning

confidence: 78%

Section: In Vitro Tlr5 Stimulationmentioning

confidence: 99%

“…This approach was also used in our work with influenza. 24 This work suggested that flagellin would be helpful as a scaffold and immunogen in our newest T. gondii work.…”

Section: Introductionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Protein nanovaccine confers robust immunity against Toxoplasma

Bissati

Zhou

Paulillo³

et al. 2017

npj Vaccines

Self Cite

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“…Additionally, PLGA NPs co-delivering whole virus antigen and multiple TLRas (TLR4a and TLR7a) have been used to elicit robust immunity against H1N1 influenza in rhesus macaques [35]. NPs built from influenza antigens through self-assembly have also been used to ensure display in the native conformations to drive cross-protection [42]. …”

Section: Biomaterials Can Improve Immunogenicity and Durability Of Vamentioning

confidence: 99%

Improving Vaccine and Immunotherapy Design Using Biomaterials

Bookstaver

Tsai

Bromberg

et al. 2018

Trends in Immunology

157

113

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A Modular Vaccine Platform Combining Self‐Assembled Peptide Cages and Immunogenic Peptides

Morris

Glennie

Lam

et al. 2019

Adv Funct Materials

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Subunit vaccines use delivery platforms to present minimal antigenic components for immunization. The benefits of such systems include multivalency, self-adjuvanting properties, and more specific immune responses. Previously, the design, synthesis, and characterization of self-assembling peptide cages (SAGEs) have been reported. In these, de novo peptides are combined to make hubs that assemble into nanoparticles when mixed in aqueous solution. Here it is shown that SAGEs are nontoxic particles with potential as accessible synthetic peptide scaffolds for the delivery of immunogenic com- ponents. To this end, SAGEs functionalized with the model antigenic peptides tetanus toxoid 632-651 and ovalbumin 323-339 drive antigen-specific responses both in vitro and in vivo, eliciting both CD4 + T cell and B cell responses.Additionally, SAGEs functionalized with the antigenic peptide hemagglutinin 518-526 from the influenza virus are also able to drive a CD8 + T cell response in vivo. This work demonstrates the potential of SAGEs to act as a modular scaffold for antigen delivery, capable of inducing and boosting specific and tailored immune responses.

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Vaccination with self-adjuvanted protein nanoparticles provides protection against lethal influenza challenge

Cited by 63 publications

References 33 publications

Protein nanovaccine confers robust immunity against Toxoplasma

Protein nanovaccine confers robust immunity against Toxoplasma

Improving Vaccine and Immunotherapy Design Using Biomaterials

A Modular Vaccine Platform Combining Self‐Assembled Peptide Cages and Immunogenic Peptides

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