DEVELOPMENT AND IMMUNOGENICITY EVALUATION OF A DNA VACCINE AGAINST A DISEASE CAUSED BY THE AVIAN INFLUENZA VIRUS SUBTYPE A/H9



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Abstract

The A/H9 avian influenza virus subtype is classified as low-pathogenic. However, this subtype remains a concern for the WHO due to its ability to undergo rapid genetic evolution and active reassortment with highly pathogenic avian influenza viruses. In this regard, there is a clear need to develop effective vaccines against this virus subtype. It is evident that nucleic acid-based vaccines possess numerous significant advantages in comparison to other vaccine types. These vaccines have the capacity to stimulate both humoral and T-cell immune responses and can be rapidly developed; their large-scale production is relatively straightforward and versatile, requiring neither work with dangerous pathogens nor high economic costs. The aim of this study was to develop a DNA vaccine against the disease caused by avian influenza virus subtype A/H9 and to evaluate its immunogenicity in a BALB/c mouse model. Materials and methods. In the present study, an immunogen encoding the hemagglutinin of the avian influenza virus subtype A/H9 was designed and produced. The transmembrane and cytoplasmic domains were excised from the native sequence, and a number of mutations were introduced to stabilize the protein. In order to obtain an immunogen structure corresponding to the native one, a T4 bacteriophage trimerization domain was added to the C-terminus. The H9 gene, which is responsible for encoding the developed immunogen, was then cloned into the pVAX1 vector. The resulting construct was named pVAX-H9. Results. Analysis of the immunogenicity of the construct demonstrated that the vaccine has the capacity to stimulate both humoral and T-cell immune responses when administered to BALB/c mice at a dose of 100 μg. Concurrently, the number of splenocytes producing IFN-γ in response to specific stimulation in the group immunized with pVAX-H9 was twice as high as in the group immunized with the recombinant protein. Conclusions. The results obtained in this study indicate the potential of the developed DNA vaccine and of the approach used for immunogen design. The pVAX-H9 DNA vaccine can be regarded as both a single vaccine and a component of combined immunization regimens.

About the authors

Vladimir A. Yakovlev

FBIS SSC VB "Vector" of Rospotrebnadzor, Department of Bioengineering, Russia

Email: yakovlev_va@vector.nsc.ru
ORCID iD: 0009-0009-4563-2099
SPIN-code: 9298-1614
Scopus Author ID: 58762858300

Junior Researcher at the Department of Bioengineering

Russian Federation, 630559, Russia, Koltsovo

Maria B. Borgoyakova

FBIS SSC VB "Vector" of Rospotrebnadzor, Department of Bioengineering, Russia

Email: borgoyakova_mb@vector.nsc.ru
ORCID iD: 0000-0002-0768-1561
SPIN-code: 8588-7391
Scopus Author ID: 57221732585

PhD in Biology, Senior Researcher at the Department of Bioengineering

Russian Federation, 630559, Russia, Koltsovo

Elena V. Yakovleva

FBIS SSC VB "Vector" of Rospotrebnadzor, Department of Bioengineering, Russia

Email: tigeeva_ev@vector.nsc.ru
ORCID iD: 0009-0001-5203-2130
SPIN-code: 7060-3976
Scopus Author ID: 58762441200

Junior Researcher at the Department of Bioengineering

Russian Federation, 630559, Russia, Koltsovo

Nadezhda B. Rudometova

FBIS SSC VB "Vector" of Rospotrebnadzor, Department of Bioengineering, Russia

Email: andreeva_nb@vector.nsc.ru
ORCID iD: 0000-0002-1684-9071
SPIN-code: 5283-6608
Scopus Author ID: 57209885373

PhD in Biology, Senior Researcher at the Department of Bioengineering

Russian Federation, 630559, Russia, Koltsovo

Kristina P. Makarova

FBIS SSC VB "Vector" of Rospotrebnadzor, Department of Bioengineering, Russia

Email: makarova_kp@vector.nsc.ru
ORCID iD: 0009-0009-2309-0137
SPIN-code: 6200-2274
Scopus Author ID: 59712680200

Intern Researcher at the Department of Bioengineering

Russian Federation, 630559, Russia, Koltsovo

Ekaterina V. Starostina

FBIS SSC VB "Vector" of Rospotrebnadzor, Department of Bioengineering, Russia

Email: starostina_ev@vector.nsc.ru
ORCID iD: 0000-0002-1733-9524
SPIN-code: 5551-1523
Scopus Author ID: 57204154694

PhD in Biology, Senior Researcher at the Department of Bioengineering

Russian Federation, 630559, Russia, Koltsovo

Danil I. Vahitov

FBIS SSC VB "Vector" of Rospotrebnadzor, Department of Bioengineering, Russia

Email: vahitov_di@vector.nsc.ru
ORCID iD: 0009-0008-0706-8119
SPIN-code: 5372-9774
Scopus Author ID: 58899053700

Intern Researcher at the Department of Bioengineering

Russian Federation, 630559, Russia, Koltsovo

Victoria R. Litvinova

FBIS SSC VB "Vector" of Rospotrebnadzor, Department of Bioengineering, Russia

Email: litvinova_vr@vector.nsc.ru
ORCID iD: 0009-0003-6524-3222
SPIN-code: 6012-2245
Scopus Author ID: 58286776600

Junior Researcher at the Department of Bioengineering

Russian Federation, 630559, Russia, Koltsovo

Denis N. Kisakov

FBIS SSC VB "Vector" of Rospotrebnadzor, Department of Bioengineering, Russia

Email: kisakov_dn@vector.nsc.ru
ORCID iD: 0000-0003-4889-6865
SPIN-code: 4915-2395
Scopus Author ID: 57231323300

Junior Researcher at the Department of Bioengineering

Russian Federation, 630559, Russia, Koltsovo

Larisa I. Karpenko

FBIS SSC VB "Vector" of Rospotrebnadzor, Department of Bioengineering, Russia

Email: karpenko@vector.nsc.ru
ORCID iD: 0000-0003-4365-8809
SPIN-code: 2026-5992
Scopus Author ID: 7005000410

Grand PhD in Biology, Associate Professor, Leading Researcher at the Department of Bioengineering

Russian Federation, 630559, Russia, Koltsovo

Alexander A. Ilyichev

FBIS SSC VB "Vector" of Rospotrebnadzor, Department of Bioengineering, Russia

Email: ilyichev@vector.nsc.ru
ORCID iD: 0000-0001-5356-0843
SPIN-code: 7401-7013
Scopus Author ID: 7006402361

Grand PhD in Biology, Professor, Chief Researcher at the Department of Bioengineering

Russian Federation, 630559, Russia, Koltsovo

Andrey P. Rudometov

FBIS SSC VB "Vector" of Rospotrebnadzor, Department of Bioengineering, Russia

Author for correspondence.
Email: rudometov_ap@vector.nsc.ru
ORCID iD: 0000-0003-2808-4309
SPIN-code: 7245-2291
Scopus Author ID: 57205188844

PhD in Biology, Acting Head of the Department of Bioengineering

Russian Federation, 630559, Russia, Koltsovo

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Copyright (c) Yakovlev V.A., Borgoyakova M.B., Yakovleva E.V., Rudometova N.B., Makarova K.P., Starostina E.V., Vahitov D.I., Litvinova V.R., Kisakov D.N., Karpenko L.I., Ilyichev A.A., Rudometov A.P.

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