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Diverse recognition of conserved orthopoxvirus CD8+ T cell epitopes in vaccinated rhesus macaques.

Vaccinia virus (VACV) induces a vigorous virus-specific CD8+ T cell response that plays an important role in control of poxvirus infection. … peptides from 16 different ORFs with 6 peptides recognized by both macaques. Comparison with other orthopoxvirus sequences revealed that 12 of these epitopes are strictly conserved between VACV, variola, and monkeypoxvirus. ELISPOT responses were also observed to eight epitopes that did not contain the canonical P3 proline. These results suggest that the virus …

Structural basis for broad orthopoxvirus neutralization by two antibodies targeting distinct L1R epitopes.

The 2022 mpox outbreak highlights the persistent threat posed by the mpox virus (MPXV) and related orthopoxviruses (OPXVs). Yet, approved antibody-based therapeutics for OPXVs are lacking. Here, we present two broadly neutralizing monoclonal antibodies (mAbs), G4 and B9, that target the MPXV M1R protein, homologous to L1R in other OPXVs. Both mAbs demonstrate cross-reactive binding and robust neutralization against multiple pathogenic OPXVs. Notably, G4 exhibits exceptional potency, neutralizing mature virions of VACV with an IC50 of 37.93 pM, whereas B9 has an IC50 of 41.13 nM. Cryo-electron …

An experimentally validated structure-based computational framework for humanisation of anti-orthopoxvirus antibodies.

BACKGROUND: The re-emergence of orthopoxviruses, most notably mpox virus (MPXV), poses a growing global public health threat. Well-characterised murine anti-orthopoxvirus antibodies are clinically limited by anti-mouse antibody responses, while traditional sequence-based humanisation often impairs antigen-binding activity. METHODS: We developed an experimentally validated structure-guided computational humanisation framework prioritising 3D architectural congruence over sequence identity, integrating Foldseek-based structural alignment and interface-residue constraints. We applied this framew…

Differentiating Mpox Infection and Vaccination Using a Validated Multiplex Orthopoxvirus IgG Serology Assay.

The resurgence of monkeypox virus (MPXV) outbreaks has increased demand for validated serological assays to assess exposure and immunity. Cross-reactivity among orthopoxivuses, stemming from high sequence conservation, complicates distinguishing antibody responses from natural MPXV infection versus vaccination or other orthopoxvirus exposures. We validated the Meso Scale Discovery (MSD) V-PLEX Orthopoxvirus Panel 1 (IgG) Kit, which quantifies antibody levels to five MPXV antigens and their vaccina virus (VACV) orthologs, following Good Clinical Laboratory Practice (GCLP) guidelines. We assesse…

Differentiating mpox infection and vaccination using a validated multiplex orthopoxvirus IgG serology assay.

UNLABELLED: The resurgence of monkeypox virus (MPXV) has increased demand for validated serological assays to assess exposure and immunity. Cross-reactivity among orthopoxviruses, stemming from high sequence conservation, complicates distinguishing antibody responses from natural MPXV infection versus vaccination or other orthopoxvirus exposures. We validated the Meso Scale Discovery (MSD) V-PLEX Orthopoxvirus Panel 1 (IgG) Kit, which quantifies antibody levels to five MPXV antigens and their vaccinia virus (VACV) orthologs, following Good Clinical Laboratory Practice guidelines. We assessed a…

Humoral Immunity Against Orthopoxvirus in Vaccinated and Unvaccinated Individuals during 2022 Mpox Outbreak.

Little is known about serological responses to MVA-BN (JYNNEOS) against mpox in elderly individuals with or without HIV. In this study, MVA-BN induced sustained IgG levels regardless of HIV status even up to one year. Birth before 1973 correlated with higher IgG. MVA-BN unvaccinated individuals with HIV had lower IgG than vaccinated.

mRNA vaccines: A promising platform for safer, more effective next-generation Orthopoxvirus immunization.

In recent work, Mucker et al.1 demonstrated that mRNA-1769 outperforms modified vaccinia Ankara (MVA), which has been deployed against recent mpox virus (MPXV) outbreaks, in reducing clinical symptoms and controlling viral replication, highlighting its potential as a scalable, safe, and effective next-generation platform for orthopoxvirus vaccination.

Одно лечение cidofovir спасает животных на прогрессивных стадиях смертельного ортопирусного заболевания.

В случае вспышки оспы у людей окно для эффективного лечения путем вакцинации вирусами вакцины (VACV), как считается, ограничивается первыми днями после контакта (p.e. Недавно мы продемонстрировали в модели мыши для оспы человека, что активная иммунизация через 2-3 дня с помощью вакцин VACV-Lister или модифицированных вакцин VACV Анкары (MVA) может спасти животных от смертельного вызова вируса эктомелии (ECTV), побудительного агента мышипокса. Настоящее исследование было проведено для определения того, может ли единая доза противовирусного цидофовира (CDV), применяемая в разное время и дозы, бу

Совпадение в аннотации оригинала
BACKGROUND: In an event of a smallpox outbreak in humans, the window for efficacious treatment by vaccination with vaccinia viruses (VACV) i … together, our data substantiate the feasibility of single post-exposure antiviral treatment to face orthopoxvirus infection.

Effect of 5-iodo-2'-deoxyuridine on vaccinia virus (orthopoxvirus) infections in mice.

There is a concern that there may be unregistered stocks of smallpox that can be used for bioterrorism or biological warfare. According to the WHO Advisory Committee on Variola Research, there is a need to develop strategies to treat smallpox infections should they reappear. It would also be important to have an effective drug at hand for the treatment of monkeypox disease in humans. We show here that 5-iodo-2'-deoxyuridine (IDU) is a potent inhibitor of vaccinia virus (VV) replication and that IDU inhibits VV DNA synthesis in a dose-dependent way. The in vivo protective effect of IDU was asse

Asymptomatic Orthopoxvirus Circulation in Humans in the Wake of a Monkeypox Outbreak among Chimpanzees in Cameroon.

Monkeypox virus is a zoonotic Orthopoxvirus (OPXV) that causes smallpox-like illness in humans. In Cameroon, human monkeypox cases were confirmed in 2018, and outbreaks in captive chimpanzees occurred in 2014 and 2016. We investigated the OPXV serological status among staff at a primate sanctuary (where the 2016 chimpanzee outbreak occurred) and residents from nearby villages, and describe contact with possible monkeypox reservoirs. We focused specifically on Gambian rats (Cricetomys spp.) because they are recognized possible reservoirs and because contact with Gambian rats was common enough t…

Ectromelia virus infections of mice as a model to support the licensure of anti-orthopoxvirus therapeutics.

The absence of herd immunity to orthopoxviruses and the concern that variola or monkeypox viruses could be used for bioterroristic activities has stimulated the development of therapeutics and safer prophylactics. One major limitation in this process is the lack of accessible human orthopoxvirus infections for clinical efficacy trials; however, drug licensure can be based on orthopoxvirus animal challenge models as described in the "Animal Efficacy Rule". One such challenge model uses ectromelia virus, an orthopoxvirus, whose natural host is the mouse and is the etiological agent of mousepox. …

Detection of human orthopoxvirus infections and differentiation of smallpox virus with real-time PCR.

We developed a real-time PCR protocol to detect orthopoxviruses (OPVs) from different clinical specimens and to separate variola virus from other OPVs. In our protocol, we used automated nucleic acid extraction system together with real-time PCR to create a simple, safe and fast procedure to obtain an initial result. The sensitivity was better by using designed hybridization probes as compared to SYBR green I for detection. The detection limit ranged from 13 to 1,300 copies per 20 microl reaction volume depending on the sample type. The PCR detected all OPVs pathogenic to human (variola, cowpo…

Новая вакцина ACAM2000 и другие методы лечения для борьбы со вспышками ортопоксивируса и биотеррорами.

Карантин, отслеживание случаев заболевания и вакцинация населения способствовали в 1980 году глобальному искоренению вируса вариолы, который является источником оспы. В период уничтожения вакцинами, включая вакцину от оспы, используемую в США, были живая вакцина от вакцины от вакцины от вакцины от вакцины от оспы и вакцины на основе коровопоксируса, которые привели к длительному и перекрестному иммунитету от вариолы и других связанных с ней оксивирусов. Эти вирусы вакцин были произведены в результате серийного распространения у одомашненных животных. Недостатки таких серийных вирусных вакцин в

Structure and mechanism of IFN-gamma antagonism by an orthopoxvirus IFN-gamma-binding protein.

Ectromelia virus (ECTV) encodes an IFN-gamma-binding protein (IFN-gammaBP(ECTV)) that disrupts IFN-gamma signaling and its ability to induce an antiviral state within cells. IFN-gammaBP(ECTV) is an important virulence factor that is highly conserved (>90%) in all orthopoxviruses, including variola virus, the causative agent of smallpox. The 2.2-A crystal structure of the IFN-gammaBP(ECTV)/IFN-gamma complex reveals IFN-gammaBP(ECTV) consists of an IFN-gammaR1 ligand-binding domain and a 57-aa helix-turn-helix (HTH) motif that is structurally related to the transcription factor TFIIA. The HTH mo…

Apoptosis during ectromelia orthopoxvirus infection is DEVDase dependent: in vitro and in vivo studies.

Ectromelia virus (EV), which causes mousepox, is a member of the orthopoxviruses that are defined as being able to suppress apoptosis. Caspase-3 is one of the key effector proteases which regulates the apoptotic cascade and which is responsible for DNA fragmentation observed during apoptosis. It is well known that viruses, especially poxviruses, can inhibit caspase activity. Here, we report that EV can regulate apoptosis in vitro, suppressing the activity of caspases recognizing the DEVD (Asp-Glu-Val-Asp) motif (caspase-3 and -7) before successful virus replication is completed. Caspase-3 acti…

Comparative analysis of the conserved region of the orthopoxvirus genome encoding the 36K and 12K proteins.

Genes encoding virus-specific proteins with molecular masses of 36 kDa and 12 kDa were mapped in HindIII-P and HindIII-U DNA fragments of va … ined. The late 36K protein is associated with virosomes but is not incorporated into the virions of orthopoxviruses.

The French Armed Forces Virology Unit: A Chronological Record of Ongoing Research on Orthopoxvirus.

Since the official declaration of smallpox eradication in 1980, the general population vaccination has ceased worldwide. Therefore, people under 40 year old are generally not vaccinated against smallpox and have no cross protection against orthopoxvirus infections. This naïve population may be exposed to natural or intentional orthopoxvirus emergences. The virology unit of the Institut de Recherche Biomédicale des Armées (France) has developed research programs on orthopoxviruses since 2000. Its missions were conceived to improve the diagnosis capabilities, to foster vaccine development, and t…

An epitope conserved in orthopoxvirus A13 envelope protein is the target of neutralizing and protective antibodies.

Primary immunization of humans with smallpox vaccine (live vaccinia virus (VACV)) consistently elicits antibody responses to six VACV virion membrane proteins, including A13. However, whether anti-A13 antibody contributes to immune protection against orthopoxviruses was unknown. Here, we isolated a murine monoclonal antibody (mAb) against A13 from a mouse that had been infected with VACV. The anti-A13 mAb bound to recombinant A13 protein with an affinity of 3.4nM and neutralized VACV mature virions. Passive immunization of mice with the anti-A13 mAb protected against intranasal VACV infection.…

Specific inhibition of orthopoxvirus replication by a small interfering RNA targeting the D5R gene.

BACKGROUND: Concerns about the potential use of smallpox in bioterrorism have stimulated interest in the development of novel antiviral treatments. Currently, there are no effective therapies against smallpox and new treatment strategies are greatly needed. METHODS: In this study, specifically designed small interfering RNAs (siRNAs), targeting five proteins essential for orthopoxvirus replication, were investigated for their ability to inhibit vaccinia virus strain Western Reserve (VACVWR) replication. RESULTS: Among these siRNAs, 100 nM siD5R-2, an siRNA targeting the D5 protein, decreased…

[Study of the effectiveness of recombinant alpha2-interferon and its inducers in primates with orthopoxvirus infection].

The interferon-inducing and antiviral activities of high-molecular interferon inducers larifan and rifastin and of gene engineering human alpha 2-interferon were studied in monkeys infected with smallpox. These agents appreciably prolonged the life span of infected monkeys. For green monkeys the drug efficacies were as follows: larifan protected 50%, rifastin 86%, and realderon 50% (if used for treatment) and 80% (if used for urgent prophylaxis) of animals from death; for Papio hamadryas the efficacy of urgent prophylaxis was 60%. Interferon accumulated in the serum as early as during the firs