The Versatile Manipulations of Self-Assembled Proteins in Vaccine Design

Nguyễn, Quốc Nhật; Kikuchi, K.; Maity, Bholanath; Ueno, Takafumi

doi:10.3390/ijms22041934

Cited by 26 publications

(20 citation statements)

References 112 publications

(150 reference statements)

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“…Nanosized self-assembled proteins are used as platforms in various biomedical implementations, including the development of new vaccine candidates [ 251 ].…”

Section: Vaccines Based On Npmentioning

confidence: 99%

The Role of Nucleoprotein in Immunity to Human Negative-Stranded RNA Viruses—Not Just Another Brick in the Viral Nucleocapsid

Šantak

Matić

2022

Viruses

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Negative-stranded RNA viruses (NSVs) are important human pathogens, including emerging and reemerging viruses that cause respiratory, hemorrhagic and other severe illnesses. Vaccine design traditionally relies on the viral surface glycoproteins. However, surface glycoproteins rarely elicit effective long-term immunity due to high variability. Therefore, an alternative approach is to include conserved structural proteins such as nucleoprotein (NP). NP is engaged in myriad processes in the viral life cycle: coating and protection of viral RNA, regulation of transcription/replication processes and induction of immunosuppression of the host. A broad heterosubtypic T-cellular protection was ascribed very early to this protein. In contrast, the understanding of the humoral immunity to NP is very limited in spite of the high titer of non-neutralizing NP-specific antibodies raised upon natural infection or immunization. In this review, the data with important implications for the understanding of the role of NP in the immune response to human NSVs are revisited. Major implications of the elicited T-cell immune responses to NP are evaluated, and the possible multiple mechanisms of the neglected humoral response to NP are discussed. The intention of this review is to remind that NP is a very promising target for the development of future vaccines.

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“…Nanosized self-assembled proteins are used as platforms in various biomedical implementations, including the development of new vaccine candidates [ 251 ].…”

Section: Vaccines Based On Npmentioning

confidence: 99%

The Role of Nucleoprotein in Immunity to Human Negative-Stranded RNA Viruses—Not Just Another Brick in the Viral Nucleocapsid

Šantak

Matić

2022

Viruses

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“…Aldolase used in our work is a rather large protein compared to viral determinants, so it can be assumed that among the antibodies produced, a significant part of antibodies will be produced specifically against aldolase and other additional domains of the recombinant proteins. Nevertheless, in numerous works on the creation of vaccines based on the viral and other proteins capable of self-assembly that form huge protein complexes (for example, consisting of 24 or 60 subunits), the formation of cross-specific or autoreactive antibodies to the protein components of the carrier has not been reported [ 16 ]. However, in this work, in addition to aldolase, we also used another trimerizer – α-helix from the Spike protein of the SARS-CoV-2, which is much smaller in size and, therefore, should “pull” the “antibody response” to itself to a lesser extent, besides, it originates from the same virus as the target antigens.…”

Section: Discussionmentioning

confidence: 99%

Development of a Platform for Producing Recombinant Protein Components of Epitope Vaccines for the Prevention of COVID-19

Karyagina

Gromov

Грунина

et al. 2021

Biochemistry Moscow

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A new platform for creating anti-coronavirus epitope vaccines has been developed. Two loop-like epitopes with lengths of 22 and 42 amino acid residues were selected from the receptor-binding motif of the Spike protein from the SARS‑CoV‑2 virus that participate in a large number of protein-protein interactions in the complexes with ACE2 and neutralizing antibodies. Two types of hybrid proteins, including one of the two selected epitopes, were constructed. To fix conformation of the selected epitopes, an approach using protein scaffolds was used. The homologue of Rop protein from the Escherichia coli ColE1 plasmid containing helix-turn-helix motif was used as an epitope scaffold for the convergence of C- and N-termini of the loop-like epitopes. Loop epitopes were inserted into the turn region. The conformation was additionally fixed by a disulfide bond formed between the cysteine residues present within the epitopes. For the purpose of multimerization, either aldolase from Thermotoga maritima , which forms a trimer in solution, or alpha-helical trimerizer of the Spike protein from SARS‑CoV‑2, was attached to the epitopes incorporated into the Rop-like protein. To enable purification on the heparin-containing sorbents, a short fragment from the heparin-binding hemagglutinin of Mycobacterium tuberculosis was inserted at the C-terminus of the hybrid proteins. All the obtained proteins demonstrated high level of immunogenicity after triplicate parenteral administration to mice. Sera from the mice immunized with both aldolase-based hybrid proteins and the Spike protein SARS‑CoV‑2 trimerizer-based protein with a longer epitope interacted with both the inactivated SARS‑CoV‑2 virus and the Spike protein receptor-binding domain at high titers. Supplementary information The online version contains supplementary material available at 10.1134/S0006297921100096.

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“…Most of the important functional systems in biology are formed by the self-assembly/self-organization of component biomolecules. As seen in cell membranes with lipids, proteins, and oligosaccharides, protein architectures with peptide segments, and formation of gene-active structures with DNA and RNA, bio-related molecules rationally assemble into functional structures through specific interactions such as hydrophobic effects, hydrogen bonding, and electrostatic interaction [ 114 , 115 , 116 ]. Based on this working principle of biomolecular assembly, self-assembly nanoarchitectonics to fabricate functional materials and structures are being widely researched using biomimetic molecules and bioconjugate components [ 117 , 118 , 119 ].…”

Section: Self-assembly Nanoarchitectonics With Bio-related Units Generalmentioning

confidence: 99%

Biomimetic and Biological Nanoarchitectonics

Ariga

2022

IJMS

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A post-nanotechnology concept has been assigned to an emerging concept, nanoarchitectonics. Nanoarchitectonics aims to establish a discipline in which functional materials are fabricated from nano-scale components such as atoms, molecules, and nanomaterials using various techniques. Nanoarchitectonics opens ways to form a more unified paradigm by integrating nanotechnology with organic chemistry, supramolecular chemistry, material chemistry, microfabrication technology, and biotechnology. On the other hand, biological systems consist of rational organization of constituent molecules. Their structures have highly asymmetric and hierarchical features that allow for chained functional coordination, signal amplification, and vector-like energy and signal flow. The process of nanoarchitectonics is based on the premise of combining several different processes, which makes it easier to obtain a hierarchical structure. Therefore, nanoarchitectonics is a more suitable methodology for creating highly functional systems based on structural asymmetry and hierarchy like biosystems. The creation of functional materials by nanoarchitectonics is somewhat similar to the creation of functional systems in biological systems. It can be said that the goal of nanoarchitectonics is to create highly functional systems similar to those found in biological systems. This review article summarizes the synthesis of biomimetic and biological molecules and their functional structure formation from various viewpoints, from the molecular level to the cellular level. Several recent examples are arranged and categorized to illustrate such a trend with sections of (i) synthetic nanoarchitectonics for bio-related units, (ii) self-assembly nanoarchitectonics with bio-related units, (iii) nanoarchitectonics with nucleic acids, (iv) nanoarchitectonics with peptides, (v) nanoarchitectonics with proteins, and (vi) bio-related nanoarchitectonics in conjugation with materials.

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The Versatile Manipulations of Self-Assembled Proteins in Vaccine Design

Cited by 26 publications

References 112 publications

The Role of Nucleoprotein in Immunity to Human Negative-Stranded RNA Viruses—Not Just Another Brick in the Viral Nucleocapsid

The Role of Nucleoprotein in Immunity to Human Negative-Stranded RNA Viruses—Not Just Another Brick in the Viral Nucleocapsid

Development of a Platform for Producing Recombinant Protein Components of Epitope Vaccines for the Prevention of COVID-19

Biomimetic and Biological Nanoarchitectonics

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