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Article ; Online: African Swine Fever Virus Infection and Cytokine Response In Vivo: An Update.

Franzoni, Giulia / Pedrera, Miriam / Sánchez-Cordón, Pedro J

2023 Volume 15, Issue 1

Abstract: African swine fever (ASF) is a hemorrhagic viral disease of domestic pigs and wild suids ( ... ...

Abstract	African swine fever (ASF) is a hemorrhagic viral disease of domestic pigs and wild suids (all
MeSH term(s)	Swine ; Animals ; African Swine Fever ; African Swine Fever Virus ; Cytokines/metabolism ; Interleukin-6/metabolism ; Interleukin-1/metabolism ; Sus scrofa
Chemical Substances	Cytokines ; Interleukin-6 ; Interleukin-1
Language	English
Publishing date	2023-01-14
Publishing country	Switzerland
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v15010233
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Article ; Online: Necropsy Procedures and Evaluation of Macroscopic Lesions of Pigs Infected with African Swine Fever Virus.

Sánchez-Cordón, Pedro J / Lean, Fabian / Bernard, Matthieu / Núñez, Alejandro

Methods in molecular biology (Clifton, N.J.)

2022 Volume 2503, Page(s) 15–49

Abstract: Pathology complements and provides a fundamental link to other disciplines for disease investigations supporting molecular biology, genetics, immunology, or virology as core basis of scientific research. Necropsies are an essential tool in veterinary ... ...

Abstract	Pathology complements and provides a fundamental link to other disciplines for disease investigations supporting molecular biology, genetics, immunology, or virology as core basis of scientific research. Necropsies are an essential tool in veterinary pathology for disease investigation and should be conducted in a routine, systematic, and standard approach. An orderly necropsy procedure will allow the prosector (veterinary clinicians or veterinary pathologists) to determine macroscopically normal or altered structures and allow, through experience, to acquire dexterity, speed, and confidence in the technique. In conjunction with standardized macroscopic scoring protocols, necropsy is a powerful tool especially when using experimental animal models in research. Here, we describe a systematic necropsy protocol to be conducted on pigs infected with African swine fever virus (ASFV). The methodology described only requires rudimentary instruments, and it is not time-consuming. In addition to performing accurate tissue and organ assessment, the technique intends the prosector to carry out sampling of organs and tissues of interest in ASFV-infected pigs.
MeSH term(s)	African Swine Fever/diagnosis ; African Swine Fever Virus ; Animals ; Swine
Language	English
Publishing date	2022-05-16
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-0716-2333-6_2
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Article ; Online: Safety and Efficacy upon Infection in Sheep with Rift Valley Fever Virus ZH548-rA2, a Triple Mutant Rescued Virus.

Moreno, Sandra / Lorenzo, Gema / López-Valiñas, Álvaro / de la Losa, Nuria / Alonso, Celia / Charro, Elena / Núñez, José I / Sánchez-Cordón, Pedro J / Borrego, Belén / Brun, Alejandro

Viruses

2024 Volume 16, Issue 1

Abstract: The introduction of three single nucleotide mutations into the genome of the virulent RVFV ZH548 strain allows for the rescue of a fully attenuated virus in mice (ZH548-rA2). These mutations are located in the viral genes encoding the RdRp and the non- ... ...

Abstract	The introduction of three single nucleotide mutations into the genome of the virulent RVFV ZH548 strain allows for the rescue of a fully attenuated virus in mice (ZH548-rA2). These mutations are located in the viral genes encoding the RdRp and the non-structural protein NSs. This paper shows the results obtained after the subcutaneous inoculation of ZH548-rA2 in adult sheep and the subsequent challenge with the parental virus (ZH548-rC1). Inoculation with the ZH548-rA2 virus caused no detectable clinical or pathological effect in sheep, whereas inoculation of the parental rC1 virus caused lesions compatible with viral infection characterised by the presence of scattered hepatic necrosis. Viral infection was confirmed via immunohistochemistry, with hepatocytes within the necrotic foci appearing as the main cells immunolabelled against viral antigen. Furthermore, the inoculation of sheep with the rA2 virus prevented the liver damage expected after rC1 virus inoculation, suggesting a protective efficacy in sheep which correlated with the induction of both humoral and cell-mediated immune responses.
MeSH term(s)	Animals ; Mice ; Sheep ; Rift Valley fever virus/genetics ; Antigens, Viral ; Genes, Viral ; Hepatocytes ; Virus Diseases
Chemical Substances	Antigens, Viral
Language	English
Publishing date	2024-01-05
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v16010087
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Article: Characterization of the Protective Cellular Immune Response in Pigs Immunized Intradermally with the Live Attenuated African Swine Fever Virus (ASFV) Lv17/WB/Rie1.

Pedrera, Miriam / Soler, Alejandro / Simón, Alicia / Casado, Nadia / Pérez, Covadonga / García-Casado, María A / Fernández-Pacheco, Paloma / Sánchez-Cordón, Pedro J / Arias, Marisa / Gallardo, Carmina

Vaccines

2024 Volume 12, Issue 4

Abstract: Candidate vaccines against African swine fever virus (ASFV) based on naturally attenuated or genetically modified viruses have the potential to generate protective immune responses, although there is no consensus on what defines a protective immune ... ...

Abstract	Candidate vaccines against African swine fever virus (ASFV) based on naturally attenuated or genetically modified viruses have the potential to generate protective immune responses, although there is no consensus on what defines a protective immune response against ASFV. Studies, especially in sensitive host species and focused on unravelling protective mechanisms, will contribute to the development of safer and more effective vaccines. The present study provides a detailed analysis of phenotypic and functional data on cellular responses induced by intradermal immunization and subsequent boosting of domestic pigs with the naturally attenuated field strain Lv17/WB/Rie1, as well as the mechanisms underlying protection against intramuscular challenge with the virulent genotype II Armenia/07 strain. The transient increase in IL-8 and IL-10 in serum observed after immunization might be correlated with survival. Protection was also associated with a robust ASFV-specific polyfunctional memory T-cell response, where CD4CD8 and CD8 T cells were identified as the main cellular sources of virus-specific IFNγ and TNFα. In parallel with the cytokine response, these T-cell subsets also showed specific cytotoxic activity as evidenced by the increased expression of the CD107a degranulation marker. Along with virus-specific multifunctional CD4CD8 and CD8 T-cell responses, the increased levels of antigen experienced in cytotoxic CD4 T cells observed after the challenge in immunized pigs might also contribute to controlling virulent infection by killing mechanisms targeting infected antigen-presenting cells. Future studies should elucidate whether the memory T-cell responses evidenced in the present study persist and provide long-term protection against further ASFV infections.
Language	English
Publishing date	2024-04-20
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2703319-3
ISSN	2076-393X
ISSN	2076-393X
DOI	10.3390/vaccines12040443
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Article ; Online: Absence of Long-Term Protection in Domestic Pigs Immunized with Attenuated African Swine Fever Virus Isolate OURT88/3 or BeninΔMGF Correlates with Increased Levels of Regulatory T Cells and Interleukin-10.

Sánchez-Cordón, Pedro J / Jabbar, Tamara / Chapman, Dave / Dixon, Linda K / Montoya, María

Journal of virology

2020 Volume 94, Issue 14

Abstract: Following short immunization protocols, naturally attenuated African swine fever virus (ASFV) isolate OURT88/3 and deletion mutant BeninΔMGF have previously been shown to induce high percentages of protection in domestic pigs against challenge with ... ...

Abstract	Following short immunization protocols, naturally attenuated African swine fever virus (ASFV) isolate OURT88/3 and deletion mutant BeninΔMGF have previously been shown to induce high percentages of protection in domestic pigs against challenge with virulent virus. The results obtained in the present study show that a single intramuscular immunization of domestic pigs with OURT88/3 or BeninΔMGF followed by a challenge with the virulent Benin 97/1 isolate at day 130 postimmunization did not trigger the mechanisms necessary to generate immunological memory able to induce long-term protection against disease. All pigs developed acute forms of acute swine fever (ASF). Gamma interferon-producing cells peaked at day 24 postimmunization, declining thereafter. Surprisingly, the levels of regulatory T cells (Tregs) and interleukin-10 (IL-10) were elevated at the end of the experiment, suggesting that regulatory components of the immune system may inhibit effective protection.
MeSH term(s)	African Swine Fever/immunology ; African Swine Fever/pathology ; African Swine Fever/prevention & control ; African Swine Fever Virus/immunology ; African Swine Fever Virus/isolation & purification ; Animals ; Interleukin-10/immunology ; Swine ; T-Lymphocytes, Regulatory/immunology ; T-Lymphocytes, Regulatory/pathology ; Vaccines, Attenuated/immunology ; Viral Vaccines/immunology
Chemical Substances	Vaccines, Attenuated ; Viral Vaccines ; Interleukin-10 (130068-27-8)
Language	English
Publishing date	2020-07-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80174-4
ISSN	1098-5514 ; 0022-538X
ISSN (online)	1098-5514
ISSN	0022-538X
DOI	10.1128/JVI.00350-20
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Article: Intrapancreatic accessory spleens in African swine fever infection of wild boar (

Porras, Néstor / Chinchilla, Blanca / Rodríguez-Bertos, Antonio / Barasona, José Á / Kosowska, Aleksandra / Vázquez-Fernández, Esther / Sánchez-Cordón, Pedro J / Sánchez-Vizcaíno, José M

Frontiers in veterinary science

2023 Volume 10, Page(s) 1306320

Abstract: Intrapancreatic accessory spleen (IPAS) is one of the most frequent congenital splenic anomalies in humans; however, studies in veterinary medicine are scarce. This study aimed to describe the macroscopic, histopathological and immunohistochemical ... ...

Abstract	Intrapancreatic accessory spleen (IPAS) is one of the most frequent congenital splenic anomalies in humans; however, studies in veterinary medicine are scarce. This study aimed to describe the macroscopic, histopathological and immunohistochemical features of 11 suspected cases of IPAS in wild boar piglets of 3-4 months old. Seven of the 11 animals were immunised with a low virulence isolate of African swine fever virus (ASFV) and subsequently challenged with a highly virulent ASFV isolate (LVI-HVI group). The remaining four animals were exclusively infected with a highly virulent isolate of ASFV (HVI group). Grossly, lesions comprised focal or multifocal reddish areas of variable shape, located on the surface of the pancreatic tail or within the parenchyma. Histological and immunohistochemical studies (anti-CD79 and CD3) confirmed the presence of IPAS in eight of the 11 cases. IPAS shared the same histological structure and alterations as those observed in the original spleen. The immunohistochemical study against ASFV revealed the presence of VP72+ cells in both the spleen and IPAS of seven of the eight piglets. The results of this study describe for the first time the presence of IPAS in ASFV infection of wild boar (
Language	English
Publishing date	2023-12-12
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2834243-4
ISSN	2297-1769
ISSN	2297-1769
DOI	10.3389/fvets.2023.1306320
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Article ; Online: Preclinical immune efficacy against SARS-CoV-2 beta B.1.351 variant by MVA-based vaccine candidates.

Pérez, Patricia / Albericio, Guillermo / Astorgano, David / Flores, Sara / Sánchez-Corzo, Cristina / Sánchez-Cordón, Pedro J / Luczkowiak, Joanna / Delgado, Rafael / Casasnovas, José M / Esteban, Mariano / García-Arriaza, Juan

Frontiers in immunology

2023 Volume 14, Page(s) 1264323

Abstract: The constant appearance of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VoCs) has jeopardized the protective capacity of approved vaccines against coronavirus disease-19 (COVID-19). For this reason, the generation ...

Abstract	The constant appearance of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VoCs) has jeopardized the protective capacity of approved vaccines against coronavirus disease-19 (COVID-19). For this reason, the generation of new vaccine candidates adapted to the emerging VoCs is of special importance. Here, we developed an optimized COVID-19 vaccine candidate using the modified vaccinia virus Ankara (MVA) vector to express a full-length prefusion-stabilized SARS-CoV-2 spike (S) protein, containing 3 proline (3P) substitutions in the S protein derived from the beta (B.1.351) variant, termed MVA-S(3Pbeta). Preclinical evaluation of MVA-S(3Pbeta) in head-to-head comparison to the previously generated MVA-S(3P) vaccine candidate, expressing a full-length prefusion-stabilized Wuhan S protein (with also 3P substitutions), demonstrated that two intramuscular doses of both vaccine candidates fully protected transgenic K18-hACE2 mice from a lethal challenge with SARS-CoV-2 beta variant, reducing mRNA and infectious viral loads in the lungs and in bronchoalveolar lavages, decreasing lung histopathological lesions and levels of proinflammatory cytokines in the lungs. Vaccination also elicited high titers of anti-S Th1-biased IgGs and neutralizing antibodies against ancestral SARS-CoV-2 Wuhan strain and VoCs alpha, beta, gamma, delta, and omicron. In addition, similar systemic and local SARS-CoV-2 S-specific CD4
MeSH term(s)	Mice ; Animals ; Humans ; SARS-CoV-2/genetics ; Vaccinia virus/genetics ; COVID-19 Vaccines ; Antibodies, Viral ; COVID-19/prevention & control ; Mice, Inbred C57BL ; Vaccines
Chemical Substances	COVID-19 Vaccines ; Antibodies, Viral ; Vaccines
Language	English
Publishing date	2023-12-12
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2023.1264323
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Article ; Online: Role of African Swine Fever Virus Proteins EP153R and EP402R in Reducing Viral Persistence in Blood and Virulence in Pigs Infected with BeninΔDP148R.

Petrovan, Vlad / Rathakrishnan, Anusyah / Islam, Muneeb / Goatley, Lynnette C / Moffat, Katy / Sanchez-Cordon, Pedro J / Reis, Ana L / Dixon, Linda K

Journal of virology

2021 Volume 96, Issue 1, Page(s) e0134021

Abstract: The limited knowledge on the role of many of the approximately 170 proteins encoded by African swine fever virus restricts progress toward vaccine development. Previously, the DP148R gene was deleted from the genome of genotype I virulent Benin 97/1 ... ...

Abstract	The limited knowledge on the role of many of the approximately 170 proteins encoded by African swine fever virus restricts progress toward vaccine development. Previously, the DP148R gene was deleted from the genome of genotype I virulent Benin 97/1 isolate. This virus, BeninΔDP148R, induced transient moderate clinical signs after immunization and high levels of protection against challenge. However, the BeninΔDP148R virus and genome persisted in blood over a prolonged period. In the current study, deletion of either EP402R or EP153R genes individually or in combination from BeninΔDP148R genome was shown not to reduce virus replication in macrophages
MeSH term(s)	African Swine Fever/immunology ; African Swine Fever/metabolism ; African Swine Fever/virology ; African Swine Fever Virus/physiology ; Animals ; Antibodies, Viral/blood ; Antibodies, Viral/immunology ; Antigens, Viral/genetics ; Antigens, Viral/immunology ; Antigens, Viral/metabolism ; Biomarkers ; Cells, Cultured ; Genetic Engineering ; Genotype ; Host-Pathogen Interactions ; Immunization ; Macrophages/immunology ; Macrophages/metabolism ; Macrophages/virology ; Sequence Deletion ; Swine ; Viral Proteins/genetics ; Viral Proteins/immunology ; Viral Proteins/metabolism ; Viral Vaccines/immunology ; Viremia/virology ; Virulence ; Virus Replication
Chemical Substances	Antibodies, Viral ; Antigens, Viral ; Biomarkers ; Viral Proteins ; Viral Vaccines
Language	English
Publishing date	2021-10-13
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80174-4
ISSN	1098-5514 ; 0022-538X
ISSN (online)	1098-5514
ISSN	0022-538X
DOI	10.1128/JVI.01340-21
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Zs.A 609: Show issues

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Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

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Article: West Nile Virus spread and differential chemokine response in the central nervous system of mice: Role in pathogenic mechanisms of encephalitis

Vidaña, Beatriz / Johnson, Nicholas / Fooks, Anthony R / Sánchez‐Cordón, Pedro J / Hicks, Daniel J / Nuñez, Alejandro

Transboundary and emerging diseases. 2020 Mar., v. 67, no. 2

2020

Abstract: West Nile virus (WNV) is a zoonotic mosquito‐borne flavivirus able to cause severe neurological disease in humans, horses and various avian species. The more severe pathological changes of neurotropic WNV infection are caused by virus neuroinvasion and/ ... ...

Abstract	West Nile virus (WNV) is a zoonotic mosquito‐borne flavivirus able to cause severe neurological disease in humans, horses and various avian species. The more severe pathological changes of neurotropic WNV infection are caused by virus neuroinvasion and/or the immunological response in the central nervous system (CNS). The extent in which inflammatory cell trafficking orchestrated by chemokines is involved in the pathogenesis of CNS lesions has not been entirely elucidated. To understand the sequence of pro‐inflammatory chemokine induction during WNV encephalitis, a murine intranasal inoculation model was used. The relationship between lesional patterns in the mice CNS, the viral antigen distribution and the expression of pro‐inflammatory chemokine (CCL2, CCL5 and CXCL10) were evaluated. Viral antigen was first observed in olfactory tract and pyriform cortex neurons, suggesting a retrograde neuronal infection from the olfactory nerve. A spatio‐temporal association between WNV antigen and perivascular cuffs development was observed. Chemokine immunostaining was widely distributed in the brain from early stages. CCL2 immunolabelling was localised in neurons, astrocytes, microglia and endothelial cells as well as mononuclear leucocytes within perivascular cuffs. In contrast, CCL5 and CXCL10 immunostaining were mainly observed in astroglia and neurons, respectively. A strong correlation was demonstrated between the presence of perivascular cuffs and CCL2 and CCL5 expression in most brain areas, while CXCL10 was only associated with inflammatory lesions in few specific regions. Importantly, a strong correlation between WNV and CCL5 distribution was observed. However, no correlation was observed between CXCL10 and viral antigen. Neurons were confirmed as the main target cells of WNV, as well as one of the sources of CCL2, CCL5 and CXCL10. This study shows the sequence and comparative distribution pattern between histological lesions, WNV antigen and chemokine expression over the infection process. Furthermore, it identifies potential targets for immune intervention to suppress damaging chemokine responses.
Keywords	West Nile virus ; astrocytes ; birds ; brain ; chemokine CCL2 ; chemokine CCL5 ; chemokine CXCL10 ; cortex ; emerging diseases ; encephalitis ; endothelial cells ; histology ; horses ; immune response ; leukocytes ; models ; nerve tissue ; neurons ; pathogenesis ; viral antigens ; viruses ; zoonoses
Language	English
Dates of publication	2020-03
Size	p. 799-810.
Publishing place	John Wiley & Sons, Ltd
Document type	Article
Note	JOURNAL ARTICLE
ZDB-ID	2414822-2
ISSN	1865-1682 ; 1865-1674
ISSN (online)	1865-1682
ISSN	1865-1674
DOI	10.1111/tbed.13401
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Modulating the immune response to SARS-CoV-2 by different nanocarriers delivering an mRNA expressing trimeric RBD of the spike protein: COVARNA Consortium.

Marcos-Villar, Laura / Perdiguero, Beatriz / Anthiya, Shubaash / Borrajo, Mireya L / Lou, Gustavo / Franceschini, Lorenzo / Esteban, Ignasi / Sánchez-Cordón, Pedro J / Zamora, Carmen / Sorzano, Carlos Óscar S / Jordá, Luis / Codó, Laia / Gelpí, Josep L / Sisteré-Oró, Marta / Meyerhans, Andreas / Thielemans, Kris / Martínez-Jiménez, Francisco / López-Vigas, Nuria / García, Felipe /

Alonso, María J / Plana, Montserrat / Esteban, Mariano / Gómez, Carmen Elena

NPJ vaccines

2024 Volume 9, Issue 1, Page(s) 53

Abstract: Vaccines based on mRNA technology have revolutionized the field. In fact, lipid nanoparticles (LNP) formulated with mRNA are the preferential vaccine platform used in the fight against SARS-CoV-2 infection, with wider application against other diseases. ... ...

Abstract	Vaccines based on mRNA technology have revolutionized the field. In fact, lipid nanoparticles (LNP) formulated with mRNA are the preferential vaccine platform used in the fight against SARS-CoV-2 infection, with wider application against other diseases. The high demand and property right protection of the most potent cationic/ionizable lipids used for LNP formulation of COVID-19 mRNA vaccines have promoted the design of alternative nanocarriers for nucleic acid delivery. In this study we have evaluated the immunogenicity and efficacy of different rationally designed lipid and polymeric-based nanoparticle prototypes against SARS-CoV-2 infection. An mRNA coding for a trimeric soluble form of the receptor binding domain (RBD) of the spike (S) protein from SARS-CoV-2 was encapsulated using different components to form nanoemulsions (NE), nanocapsules (NC) and lipid nanoparticles (LNP). The toxicity and biological activity of these prototypes were evaluated in cultured cells after transfection and in mice following homologous prime/boost immunization. Our findings reveal good levels of RBD protein expression with most of the formulations. In C57BL/6 mice immunized intramuscularly with two doses of formulated RBD-mRNA, the modified lipid nanoparticle (mLNP) and the classical lipid nanoparticle (LNP-1) were the most effective delivery nanocarriers at inducing binding and neutralizing antibodies against SARS-CoV-2. Both prototypes fully protected susceptible K18-hACE2 transgenic mice from morbidity and mortality following a SARS-CoV-2 challenge. These results highlight that modulation of mRNAs immunogenicity can be achieved by using alternative nanocarriers and support further assessment of mLNP and LNP-1 prototypes as delivery vehicles for mRNA vaccines.
Language	English
Publishing date	2024-03-06
Publishing country	England
Document type	Journal Article
ISSN	2059-0105
ISSN (online)	2059-0105
DOI	10.1038/s41541-024-00838-8
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