Monoclonal Antibodies in Light of Mpox Outbreak: Current Research, Therapeutic Targets, and Animal Models

Antibodies, Journal Year: 2025, Volume and Issue: 14(1), P. 20 - 20

Published: Feb. 26, 2025

The rapid rise in monkeypox virus infections among humans from 2022 to 2024 has captured the attention of global healthcare community. In light lack mandatory vaccination and limited data on next-generation vaccines for prevention, urgent development therapeutic agents become a priority. One promising approach involves use neutralizing monoclonal antibodies. This review highlights significant advancements search antibodies against human pathogenic orthopoxviruses, particularly focusing their potential application virus. We also analyze viral proteins that serve as targets identifying capable wide range viruses. Finally, we deemed it essential address challenges associated with selecting an animal model can adequately reflect infectious process each orthopoxvirus species humans.

Language: Английский

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Chemokines cooperate with TNF to provide protective anti-viral immunity and to enhance inflammation

Nature Communications, Journal Year: 2018, Volume and Issue: 9(1)

Published: April 27, 2018

The role of cytokines and chemokines in anti-viral defense has been demonstrated, but their relative contribution to protective responses vivo is not fully understood. Cytokine response modifier D (CrmD) a secreted receptor for TNF lymphotoxin containing the smallpox virus-encoded chemokine (SECRET) domain expressed by ectromelia virus, causative agent smallpox-like disease mousepox. Here we show that CrmD an essential virulence factor controls natural killer cell activation allows progression fatal mousepox, demonstrate both SECRET binding domains are required full activity. Vaccination with recombinant protects animals from lethal These results indicate specific set enhance inflammatory mediated lymphotoxin, illustrate how viruses optimize anti-TNF strategies addition as soluble decoy receptors.

Language: Английский

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Protection of Rabbits and Immunodeficient Mice against Lethal Poxvirus Infections by Human Monoclonal Antibodies

PLoS ONE, Journal Year: 2012, Volume and Issue: 7(11), P. e48706 - e48706

Published: Nov. 2, 2012

Smallpox (variola virus) is a bioweapon concern. Monkeypox growing zoonotic poxvirus threat. These problems have resulted in extensive efforts to develop potential therapeutics that can prevent or treat potentially lethal infections humans. Monoclonal antibodies (mAbs) against smallpox are conservative approach this problem, as the licensed human vaccine (vaccinia virus, VACV) primarily works on basis of protective antibody responses smallpox. Fully mAbs (hmAbs) vaccinia H3 (H3L) and B5 (B5R), targeting both mature virion (MV) extracellular enveloped (EV) forms, been developed for use Post-exposure prophylaxis was assessed murine rabbit animal models. Therapeutic efficacy three good laboratory practices (GLP) studies examining severe combined immunodeficiency mice (SCID) given VACV infection. Pre-exposure combination hmAb therapy provided significantly better protection disease death than either single immune globulin (VIG). mAb significant death, appeared fully cure infection ≥50% SCID mice. then two post-exposure rabbitpox (RPXV). In first study, rabbits were infected with RPVX hmAbs at 48 hrs post-infection, 1 hr 72 post-infection. Rabbits groups receiving 100% protected from death. second treated animals anti-B5 protected. findings suggest treatment may be effective controlling immunocompetent immunodeficient

Language: Английский

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Tricked or trapped—Two decoy mechanisms in host–pathogen interactions

PLoS Pathogens, Journal Year: 2018, Volume and Issue: 14(2), P. e1006761 - e1006761

Published: Feb. 15, 2018

Antagonistic interactions between hosts and pathogens frequently result in arms races.The host attempts to recognise the pathogen inhibit its growth spread, whereas tries subvert recognition suppress responses.These antagonistic drive evolution of 'decoys' both pathogens.In host-pathogen interactions, term decoy describes molecules that mimic a component at interface is manipulated during infection.Decoys undergo same manipulation as they mimic, but serve opposite role, either by preventing or triggering molecular event.At least three different types have been defined, described detail below.However, these models cause confusion on how function mechanistically.Here, we discuss decoys with examples classify them according two distinct mechanisms. Receptor decoys: Mimics absorb ligandsSome use 'Receptor decoys' interfere immune signalling (Fig 1A).Examples are found large DNA viruses.Some viruses acquired diverse set through recombination events [1].These typically encode for viral versions receptor homologs bind chemokines cytokines prevent efficient host.For example, ectromelia virus (causative mouse pox) encodes Type 1-interferon binding protein (T1-IFNbp), essential virulence [2].T1-IFNbp mimics interferon attaches uninfected cells close infection site liver spleen.By T1-IFN, T1-IFNbp facilitates spread impairs defence [3].Therefore, this virus-derived absorbs key signal signalling.A similar example pathogen-derived extracellular Protein-6 (Ecp6), Lysin Motif (LysM)-containing effector secreted fungal Cladosporium fulvum tomato plants.Ecp6 suppresses chitin therefore instrumental C. [4].Chitin an cell walls, many plants can sense LysM-containing receptors such Chitin Elicitor Kinase-1 (CERK1) homologs.Interestingly, Ecp6 captures oligomers high affinity thought outcompete LysM-based [5].Therefore, chitin-binding capacity acts host.Interestingly, effectors widespread amongst plant pathogens, so absorption LysM appears be commonly used strategy [6].

Language: Английский

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TLR3 and TLR9 Agonists Improve Postexposure Vaccination Efficacy of Live Smallpox Vaccines

PLoS ONE, Journal Year: 2014, Volume and Issue: 9(10), P. e110545 - e110545

Published: Oct. 28, 2014

Eradication of smallpox and discontinuation the vaccination campaign resulted in an increase percentage unvaccinated individuals, highlighting need for postexposure efficient countermeasures case accidental or deliberate viral release. Intranasal infection mice with ectromelia virus (ECTV), a model human smallpox, is curable by high vaccine dose given up to 3 days postexposure. To further extend this protective window reduce morbidity, were vaccinated Vaccinia-Lister, conventional Modified Vaccinia Ankara, highly attenuated conjunction TLR3 TLR9 agonists. We show that co-administration agonist poly(I:C) even 5 conferred protection, avoiding dose. Efficacious treatments prevented death, ameliorated disease symptoms, reduced load maintained tissue integrity target organs. Protection was associated significant elevation serum IFNα anti-vaccinia IgM antibodies, modulation IFNγ response, balanced activation NK T cells. agonists (CpG ODNs) less than poly(I:C). type 1 IFN protection achievable without co-vaccination, requiring sufficient amount antigens infective agent vaccine. This study demonstrated therapeutic potential immune TLR activation, allowing alleviate symptoms vaccination.

Language: Английский

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Viral dedication to vigorous destruction of interferon receptors

Virology, Journal Year: 2018, Volume and Issue: 522, P. 19 - 26

Published: July 6, 2018

Language: Английский

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MyD88-Dependent Immunity to a Natural Model of Vaccinia Virus Infection Does Not Involve Toll-Like Receptor 2

Journal of Virology, Journal Year: 2014, Volume and Issue: 88(6), P. 3557 - 3567

Published: Jan. 9, 2014

ABSTRACT Although the pattern recognition receptor Toll-like 2 (TLR2) is typically thought to recognize bacterial components, it has been described alter induction of both innate and adaptive immunity a number viruses, including vaccinia virus (VACV). However, many pathogens that reportedly encode TLR2 agonists may actually be artifactually contaminated during preparation, possibly with cellular debris or merely molecules sensitize cells activated by authentic agonists. In humans mice, most relevant natural route infection VACV through intradermal skin. Therefore, we examined requirement for its signaling adaptor MyD88 in protective after infection. We find although preparations vitro have minor role preventing dissemination following systemic large doses virus, wholly disposable control replication contrast, required efficient CD4 T cell B responses local even not induce inflammation, inflammatory cytokine production, recruitment restrict from spreading systemically peripheral Thus, an effective antiviral response does require MyD88, but These findings emphasize importance studying routes when examining sensing mechanisms. IMPORTANCE Vaccinia (VACV) provides backbone some widely used successful viral vaccine vectors also related human Cantagalo molluscum contagiosum infect skin patients. vital understand mechanisms strong immune dermal Here, compare ability molecule influence

Language: Английский

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Memory CD8 + T Cells Can Outsource IFN-γ Production but Not Cytolytic Killing for Antiviral Protection

Cell Host & Microbe, Journal Year: 2013, Volume and Issue: 13(5), P. 546 - 557

Published: May 1, 2013

Language: Английский

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Comparison of Host Gene Expression Profiles in Spleen Tissues of Genetically Susceptible and Resistant Mice during ECTV Infection

BioMed Research International, Journal Year: 2017, Volume and Issue: 2017, P. 1 - 13

Published: Jan. 1, 2017

Ectromelia virus (ECTV), the causative agent of mousepox, has emerged as a valuable model for investigating host- Orthopoxvirus relationship it relates to pathogenesis and immune response. ECTV is mouse-specific causes high mortality in susceptible mice strains, including BALB/c C3H, whereas C57BL/6 129 strains are resistant disease. To understand host genetic factors different mouse during infection, we carried out microarray analysis spleen tissues derived from mice, respectively, at 3 10 days after infection. Differential Expression Genes (DEGs) analyses revealed distinct differences gene profiles mice. The generated more DEGs than Additionally, ontology KEGG pathway showed were involved innate immunity, apoptosis, metabolism, cancer-related pathways, while largely MAPK signaling leukocyte transendothelial migration. Furthermore, strong induction interferon-induced genes, which, however, weaker Collectively, differential transcriptome with infection will be crucial further uncovering molecular mechanisms interaction.

Language: Английский

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Redundant Function of Plasmacytoid and Conventional Dendritic Cells Is Required To Survive a Natural Virus Infection

Journal of Virology, Journal Year: 2015, Volume and Issue: 89(19), P. 9974 - 9985

Published: July 23, 2015

ABSTRACT Viruses that spread systemically from a peripheral site of infection cause morbidity and mortality in the human population. Innate myeloid cells, including monocytes, macrophages, monocyte-derived dendritic cells (mo-DC), (DC), respond early during viral to control replication, reducing virus site. Ectromelia (ECTV), an orthopoxvirus naturally infects mouse, spreads results death susceptible mice. While phagocytic have requisite role response ECTV, requirement for individual cell populations acute immune responses is unclear. In this study, variety myeloid-specific depletion methods were used dissect roles subsets survival ECTV infection. We showed DC are primary producers type I interferons (T1-IFN), cytokines survival, following DC, but not or granulocytes, required mice Depletion either plasmacytoid (pDC) alone lymphoid-resident subset (CD8α + DC) did confer lethal susceptibility ECTV. However, function at least one pDC CD8α infection, as depleted both challenge. The presence these sufficient cytokine production reduces replication spread, facilitating IMPORTANCE Prior eradication variola virus, causes smallpox, one-third infected people succumbed disease. Following successful vaccination rates with smallpox vaccine significantly dropped. There now increasing incidence zoonotic infections which there no effective treatments. Moreover, safety great concern, complications may arise, resulting morbidity. Like many viruses significant diseases, orthopoxviruses become systemic. This study elucidates innate controlling causative agent mousepox. report redundancy two mediated by presents potential target therapies rational design.

Language: Английский

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