Open Access

Frontiers in Immunology, volume 14

Single-domain antibody delivery using an mRNA platform protects against lethal doses of botulinum neurotoxin A

Panova Eugenia A. ^{1, 2, 3}

Kleymenov Denis A. ¹

Shcheblyakov Dmitry V. ¹

Bykonia Evgeniia N. ¹

Mazunina Elena P. ¹

Dzharullaeva Alina S. ¹

Zolotar Anastasia N. ¹

Derkaev Artem A. ¹

Esmagambetov Ilias B. ¹

Sorokin Ivan I. ^{1, 3}

Usachev Evgeny V. ¹

Noskov Anatoly N. ¹

Ivanov Igor A ^{1, 4}

Zatsepin Timofei S ⁵

Dmitriev Sergey E. ^{1, 2, 3}

Gushchin Vladimir A. ^{1, 6}

Naroditsky Boris S. ¹

Logunov Denis Y. ¹

Gintsburg Alexander L. ^{1, 7}

Hide authors affiliations Show authors affiliations: 7 affiliations

National Research Centre for Epidemiology and Microbiology named after Honorary Academician N F Gamaleya of the Ministry of Health of the Russian Federation, Russia |

Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Russia |

Belozersky Institute of Physico-chemical Biology, Lomonosov Moscow State University, Russia |

⁴

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Russia |

⁵

Chemistry Department, Lomonosov Moscow State University, Russia |

⁶

Department of Virology, Lomonosov Moscow State University, Russia |

⁷

Infectiology Department, I. M. Sechenov First Moscow State Medical University, Russia |

Publication type: Journal Article

Publication date: 2023-02-14

Frontiers Media S.A.

Journal: Frontiers in Immunology

Quartile SCImago

Quartile WOS

Impact factor: 7.3

ISSN: 16643224

DOI: 10.3389/fimmu.2023.1098302

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Immunology

Immunology and Allergy

Abstract

Single-domain antibodies (sdAbs, VHHs, or nanobodies) are a promising tool for the treatment of both infectious and somatic diseases. Their small size greatly simplifies any genetic engineering manipulations. Such antibodies have the ability to bind hard-to-reach antigenic epitopes through long parts of the variable chains, the third complementarity-determining regions (CDR3s). VHH fusion with the canonical immunoglobulin Fc fragment allows the Fc-fusion single-domain antibodies (VHH-Fc) to significantly increase their neutralizing activity and serum half-life. Previously we have developed and characterized VHH-Fc specific to botulinum neurotoxin A (BoNT/A), that showed a 1000-fold higher protective activity than monomeric form when challenged with five times the lethal dose (5 LD₅₀) of BoNT/A. During the COVID-19 pandemic, mRNA vaccines based on lipid nanoparticles (LNP) as a delivery system have become an important translational technology that has significantly accelerated the clinical introduction of mRNA platforms. We have developed an mRNA platform that provides long-term expression after both intramuscular and intravenous application. The platform has been extensively characterized using firefly luciferase (Fluc) as a reporter. An intramuscular administration of LNP-mRNA encoding VHH-Fc antibody made it possible to achieve its rapid expression in mice and resulted in 100% protection when challenged with up to 100 LD₅₀ of BoNT/A. The presented approach for the delivery of sdAbs using mRNA technology greatly simplifies drug development for antibody therapy and can be used for emergency prophylaxis.

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Citations by journals

	1
Current Opinion in HIV and AIDS	Current Opinion in HIV and AIDS, 1, 16.67% Current Opinion in HIV and AIDS 1 publication, 16.67%
Signal Transduction and Targeted Therapy	Signal Transduction and Targeted Therapy, 1, 16.67% Signal Transduction and Targeted Therapy 1 publication, 16.67%
Biochemistry (Moscow)	Biochemistry (Moscow), 1, 16.67% Biochemistry (Moscow) 1 publication, 16.67%
	1

Citations by publishers

	1
Wolters Kluwer Health	Wolters Kluwer Health, 1, 16.67% Wolters Kluwer Health 1 publication, 16.67%
Springer Nature	Springer Nature, 1, 16.67% Springer Nature 1 publication, 16.67%
Pleiades Publishing	Pleiades Publishing, 1, 16.67% Pleiades Publishing 1 publication, 16.67%
	1

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Panova E. A. et al. Single-domain antibody delivery using an mRNA platform protects against lethal doses of botulinum neurotoxin A // Frontiers in Immunology. 2023. Vol. 14.

GOST all authors (up to 50) Copy

Panova E. A., Kleymenov D. A., Shcheblyakov D. V., Bykonia E. N., Mazunina E. P., Dzharullaeva A. S., Zolotar A. N., Derkaev A. A., Esmagambetov I. B., Sorokin I. I., Usachev E. V., Noskov A. N., Ivanov I. A., Zatsepin T. S., Dmitriev S. E., Gushchin V. A., Naroditsky B. S., Logunov D. Y., Gintsburg A. L. Single-domain antibody delivery using an mRNA platform protects against lethal doses of botulinum neurotoxin A // Frontiers in Immunology. 2023. Vol. 14.

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RIS Copy

TY - JOUR

DO - 10.3389/fimmu.2023.1098302

UR - https://doi.org/10.3389%2Ffimmu.2023.1098302

TI - Single-domain antibody delivery using an mRNA platform protects against lethal doses of botulinum neurotoxin A

T2 - Frontiers in Immunology

AU - Panova, Eugenia A.

AU - Kleymenov, Denis A.

AU - Shcheblyakov, Dmitry V.

AU - Bykonia, Evgeniia N.

AU - Mazunina, Elena P.

AU - Dzharullaeva, Alina S.

AU - Zolotar, Anastasia N.

AU - Derkaev, Artem A.

AU - Esmagambetov, Ilias B.

AU - Sorokin, Ivan I.

AU - Usachev, Evgeny V.

AU - Noskov, Anatoly N.

AU - Ivanov, Igor A

AU - Zatsepin, Timofei S

AU - Dmitriev, Sergey E.

AU - Gushchin, Vladimir A.

AU - Naroditsky, Boris S.

AU - Logunov, Denis Y.

AU - Gintsburg, Alexander L.

PY - 2023

DA - 2023/02/14 00:00:00

PB - Frontiers Media S.A.

VL - 14

SN - 1664-3224

ER -

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@article{2023_Panova,

author = {Eugenia A. Panova and Denis A. Kleymenov and Dmitry V. Shcheblyakov and Evgeniia N. Bykonia and Elena P. Mazunina and Alina S. Dzharullaeva and Anastasia N. Zolotar and Artem A. Derkaev and Ilias B. Esmagambetov and Ivan I. Sorokin and Evgeny V. Usachev and Anatoly N. Noskov and Igor A Ivanov and Timofei S Zatsepin and Sergey E. Dmitriev and Vladimir A. Gushchin and Boris S. Naroditsky and Denis Y. Logunov and Alexander L. Gintsburg},

title = {Single-domain antibody delivery using an mRNA platform protects against lethal doses of botulinum neurotoxin A},

journal = {Frontiers in Immunology},

year = {2023},

volume = {14},

publisher = {Frontiers Media S.A.},

month = {feb},

url = {https://doi.org/10.3389%2Ffimmu.2023.1098302},

doi = {10.3389/fimmu.2023.1098302}

}

Found error?

Publisher

Frontiers Media S.A.

Journal

Frontiers in Immunology

Quartile SCImago

Quartile WOS

Impact factor

7.3

ISSN

16643224 (Electronic)

News

Профилактический РНК-препарат защитил мышей от ботулотоксина