MECHANISMS OF IMMUNE RESPONSE AND PROSPECTS FOR DNA VACCINES AGAINST AFRICAN SWINE FEVER (review)

Sereda, Alexey D.; Imatdinov, A.R.; Dubrovskaya, O.A.; Kolbasov, Denis

doi:10.15389/agrobiology.2017.6.1069eng

Cited by 3 publications

(1 citation statement)

References 28 publications

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“…Строение вирусной оболочки, в состав которой входит большое количество гликозилированных белков, позволяет вирусу «маскировать» антигенные детерминанты и избегать воздействия иммунной системы хозяина. Одним из подходов к созданию средств лечения и профилактики африканской чумы свиней стало изучение роли поверхностных антигенов вируса (белка CD2v, C-лектиноподобного белка, белка мембраны вируса P54) (6,8).…”

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

Katorkina¹,

Цыбанов²,

Malogolovkin³

2019

s-h. biol.

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Основные требования к современным вакцинным препаратам -эффективность, надежность и отсутствие побочных действий (безвредность). Повышение требований к безопасности и чистоте препаратов стимулировало как развитие традиционных препаратов, так и создание искусственных вакцин нового поколения -субъединичных, рекомбинантных, антиидиотипических, ДНК-вакцин и др. Технология получения рекомбинантных белков доказала свое преимущество при разработке широкого спектра терапевтических и лечебных препаратов против инфекционных болезней человека и животных (S. Khan с соавт., 2016). В 2011 году создано шесть лекарственных препаратов на основе технологии Fc-фьюжирования белков. Большинство этих Fc-химерных протенинов влияют на рецептор-лигандные взаимодействия как антагонисты, либо блокирующие связывание рецептора, например Энбрел (этанерцепт; «Amgen», США), Залтрап (афлиберцепт; «Sanofi», Франция), Аркалист (рилонацепт; «Regeneron», США), либо прямо стимулирующие рецепторную функцию, вызывающие снижение (Амевив -алефацепт; «Astellas», США) или повышение (Энплейт -ромиплостим; «Amgen», США) активности иммунного ответа. В представленном обзоре мы уделили особое внимание наиболее актуальным результатам, полученным в последние годы при применении технологии Fc-слияния для создании вакцин против вирусных и бактериальных агентов. В таких химерных последовательностях Fc-фрагмент IgG (Fc-IgG) и целевой терапевтический белок представляют собой единый гибридный белковый продукт (V. Pechtner с соавт., 2017). При слиянии шарнирный участок Fc-IgG играет роль гибкого спейсера между терапевтическим белком и константной частью иммуноглобулина, предотвращая возможное негативное влияние двух функциональных доменов друг на друга. Препараты на основе химерных Fcбелков делятся на три типа: рецептор-Fc, пептид-Fc и мономер-Fc. Полученные с помощью этой технологии протеины имеют бóльший терапевтический потенциал, так как они связаны с Fcдоменом, который обеспечивает таргетное увеличение показателей фармакокинетики у гибридного белка. Наличие Fc-домена удлиняет период полувыведения белков из плазмы крови, что продлевает терапевтическую активность, а также приводит к более медленному почечному клиренсу для молекул большего размера. Компилируя основные экспериментальные данные по применению технологии Fc-слияния для таких патогенов, как вирус иммунодефицита человека (D. Capon с соавт., 1989), вирус Эбола (K. Konduru с соавт., 2011), вирус лихорадки Денге (M.Y. Kim с соавт., 2018), вирус гриппа (L. Du с соавт., 2011), Mycobacterium tuberculosis (S. Soleimanpour с соавт., 2015), вирус классической чумы свиней (Z. Liu с соавт., 2017), мы обсуждаем основные критические аспекты механизма действия, дизайна и производства Fc-слитных белков. Таргетная активации эффекторных систем организма позволяет повысить протективный потенциал иммуногенных молекул и расширить область их применения. Особое внимание в обзоре уделено использованию Fc-слитых белков в качестве вакцин против инфекционных болезней человека и животных. На примере вируса африканской чумы свиней...

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

Katorkina¹,

Цыбанов²,

Malogolovkin³

2019

s-h. biol.

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Transcriptome profile of spleen tissues from locally-adapted Kenyan pigs (Sus scrofa) experimentally infected with three varying doses of a highly virulent African swine fever virus genotype IX isolate: Ken12/busia.1 (ken-1033)

et al. 2022

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Background African swine fever (ASF) is a lethal hemorrhagic disease affecting domestic pigs resulting in up to 100% mortality rates caused by the ASF virus (ASFV). The locally-adapted pigs in South-western Kenya have been reported to be resilient to disease and harsh climatic conditions and tolerate ASF; however, the mechanisms by which this tolerance is sustained remain largely unknown. We evaluated the gene expression patterns in spleen tissues of these locally-adapted pigs in response to varying infective doses of ASFV to elucidate the virus-host interaction dynamics. Methods Locally adapted pigs (n = 14) were experimentally infected with a high dose (1x106HAD50), medium dose (1x104HAD50), and low dose (1x102HAD50) of the highly virulent genotype IX ASFV Ken12/busia.1 (Ken-1033) isolate diluted in PBS and followed through the course of infection for 29 days. The in vivo pig host and ASFV pathogen gene expression in spleen tissues from 10 pigs (including three from each infective group and one uninfected control) were analyzed in a dual-RNASeq fashion. We compared gene expression between three varying doses in the host and pathogen by contrasting experiment groups against the naïve control. Results A total of 4954 differentially expressed genes (DEGs) were detected after ASFV Ken12/1 infection, including 3055, 1771, and 128 DEGs in the high, medium, and low doses, respectively. Gene ontology and KEGG pathway analysis showed that the DEGs were enriched for genes involved in the innate immune response, inflammatory response, autophagy, and apoptosis in lethal dose groups. The surviving low dose group suppressed genes in pathways of physiopathological importance. We found a strong association between severe ASF pathogenesis in the high and medium dose groups with upregulation of proinflammatory cytokines and immunomodulation of cytokine expression possibly induced by overproduction of prostaglandin E synthase (4-fold; p < 0.05) or through downregulation of expression of M1-activating receptors, signal transductors, and transcription factors. The host-pathogen interaction resulted in induction of expression of immune-suppressive cytokines (IL-27), inactivation of autophagy and apoptosis through up-regulation of NUPR1 [5.7-fold (high dose) and 5.1-fold (medium dose) [p < 0.05] and IL7R expression. We detected repression of genes involved in MHC class II antigen processing and presentation, such as cathepsins, SLA-DQB1, SLA-DOB, SLA-DMB, SLA-DRA, and SLA-DQA in the medium and high dose groups. Additionally, the host-pathogen interaction activated the CD8+ cytotoxicity and neutrophil machinery by increasing the expression of neutrophils/CD8+ T effector cell-recruiting chemokines (CCL2, CXCL2, CXCL10, CCL23, CCL4, CXCL8, and CXCL13) in the lethal high and medium dose groups. The recovered pigs infected with ASFV at a low dose significantly repressed the expression of CXCL10, averting induction of T lymphocyte apoptosis and FUNDC1 that suppressed neutrophilia. Conclusions We provide the first in vivo gene expression profile data from locally-adapted pigs from south-western Kenya following experimental infection with a highly virulent ASFV genotype IX isolate at varying doses that mimic acute and mild disease. Our study showed that the locally-adapted pigs induced the expression of genes associated with tolerance to infection and repression of genes involved in inflammation at varying levels depending upon the ASFV dose administered.

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Analysis of immunodominant African swine fever virus peptides for candidate vaccine design

Ефимова¹,

Galeeva²,

Khamidullina

et al. 2023

Agrarnaâ nauka

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Relevance. Prevention and control of ASF is significantly hampered by the lack of available vaccines and effective therapeutic measures. The ASF virus is capable of interfering with various cellular signaling pathways, leading to immunomodulation, which makes the development of an effective vaccine extremely difficult. Given the various limitations of known strategies for the development of ASF vaccines, the search for promising platforms for the development of safe and effective drugs to combat the virus is ongoing. The basis for the design of candidate vaccines is the choice of immunogenic peptides that provide stable humoral and cellular immune responses and the identification of potential targets for immune responses.Methods. In this study, 31 candidate amino acid sequences of more than 100 strains and epizootic isolates of the African swine fever virus was analyzed using standard bioinformatic methods.Results. Based on the number of T- and B-cell epitopes identified during the initial analysis, the type and severity of the immune response in target animals, it was found that the proteins p72 (B646L), p30 (CP204L), p54 (E183L), pp62 (CP530R), pp220 (CP2475L) have the greatest immunogenic potential. For the analyzed proteins, the N- and O-glycosylation sites, the localization of signal peptides and transmembrane domains were determined in silico, and their main physicochemical properties were predicted. The application of the proposed approaches made it possible to select potentially immunogenic epitopes of ASFV proteins, which in the future will be used to design new candidate vector vaccines. Given the number of antigenic determinants, the considered proteins, in our opinion, have a significant vaccine potential, however, real data on their immunogenicity will be established during practical testing of the developed vector constructs.

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MECHANISMS OF IMMUNE RESPONSE AND PROSPECTS FOR DNA VACCINES AGAINST AFRICAN SWINE FEVER (review)

Cited by 3 publications

References 28 publications

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

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

Transcriptome profile of spleen tissues from locally-adapted Kenyan pigs (Sus scrofa) experimentally infected with three varying doses of a highly virulent African swine fever virus genotype IX isolate: Ken12/busia.1 (ken-1033)

Analysis of immunodominant African swine fever virus peptides for candidate vaccine design

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