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doi: 10.15389/agrobiology.2019.4.642eng

UDC: 573.6.086.83:577.21]:615.371

Acknowledgements:
Supported financially by Russian Foundation for Basic Research, grant mol_а No. 18-316-00092

 

RESULTS OF Fc-PROTEIN FUSION TECHNOLOGY APPLICATION FOR VACCINE DESIGN AGAINST INFECTIOUS DISEASES OF ANIMALS AND HUMAN (review)

E.I. Katorkina, S.Zh. Tsybanov, A.S. Malogolovkin

Federal Research Center for Virology and Microbiology, 1, ul. Akademika Bakuleva, pos. Vol’ginskii, Petushinskii Region, Vladimir Province, 601125 Russia, e-mail elena.fadeeva.1990@inbox.ru, cybanov@mail.ru, AMalogolovkin@vniivvim.ru (corresponding author ✉ )

ORCID:
Katorkina E.I. orcid.org/0000-0003-3329-0182
Malogolovkin A.S. orcid.org/0000-0003-1352-1780
Tsybanov S.Zh. orcid.org/0000-0002-4919-3080

Received November 27, 2018

 

The main criteria for current vaccines design are effectiveness, efficaciousness and safety. Increasing requirements for vaccine safety and purity push forward not only classical vaccine development, but also new generation vaccine technology, including sub-unit, recombinant, anti-idiotypic, DNA vaccines etc. This recombinant technology has already demonstrated its advantage, efficaciousness and safety in a large field of therapeutic and curative drug development for animal and human (S. Khan et al., 2016). In 2011, six novel drugs were created based on the new Fc-fusion protein technology. Most of the newly developed drugs affect receptor-ligand interactions, acting as antagonists by blocking direct receptor binding, i.e. EnbrelÒ (etanercept; Amgen, USA), ZaltrapÒ (aflibercept; Sanofi, France), ArcalystÒ (rilonacept; Regeneron, USA), or as agonists for direct stimulation of receptor function which augment immune response as AmeviveÒ (alefacept, Astellas, USA) does, or decrease immune response as NplateÒ (romiplostim; Amgen, USA) does. In this review, we pay attention to the most relevant results from the last few years for virus and bacterial vaccine designed based on Fc-fusion technology. The Fc-chimeras are hybrid sequences in which Fc-fragment of IgG (Fc-IgG) and targeted therapeutic protein are fused in an entire protein molecule (V. Pechtner et al., 2017). In this fusion, the hinge region of Fc-IgG is a flexible spacer between therapeutic protein and conservative part of IgG. It helps to minimize potential negative effect of two functional domains to each other. Therapeutic drugs based on Fc-fusion proteins are divided in three types, the receptor-Fc, peptide-Fc, and monomer-Fc. The Fc-fused proteins have tremendous therapeutic potential, since Fc domain in this molecules helps to specifically augment the pharmacodynamics values. Presence of Fc-domain in hybrid molecules prolongs half elimination of protein from plasma, which extends drug therapeutic activity and slows down kidney clearance for large molecules. Here, we summarize the most significant experimental data of Fc-fusion technology application against such pathogens as human immunodeficiency virus (D. Capon et al., 1989), Ebola virus (K. Konduru et al., 2011), Dengue virus (M.Y. Kim et al., 2018), influenza virus (L. Du et al., 2011), Mycobacterium tuberculosis (S. Soleimanpour et al., 2015), classical swine fever virus(Z. Liu et al., 2017). We also discuss the critical aspects of mechanism of action, drug design and Fc-fused protein production. Targeted activation of effector systems boosts protective potential of immunogenic molecules and broadens its application. The interest of this review is focused on an application of Fc-fused proteins as potential vaccines against infectious human and animal diseases. We also briefly discuss the perspectives of Fc-fused antigens for novel effective medicine developments using African swine fever virus as an example.

Keywords: Fc fragment, human immunodeficiency virus, Ebola virus, influenza virus, tuberculosis, classical swine fever virus, African swine fever virus, vaccination.

 

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